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Prepared by:
Michel Cucherat, MD, PhD
Faculte de medecine LaennecLyon, France
mcu@upcl.univ-lyon1.fr
Drug eluting stents
A systematic review and meta-analysis of randomized clinical trials
2008 - 10 - 14
Prepared forHAS
Part or all of the information presented in this document may be unpublished material and should be treated asthe confidential property of HAS, not to be divulged to unauthorized persons, in any form, including
publications and presentations, without the written consent of HAS.
2
CONTENTS 3
Contents
I Unparticular patients 7
1 Overview of available evidence for unparticular patients 91.1 Main results for Unparticular patients . . . . . . . . . . . . . . . . . . . . . . . . 141.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 141.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 141.4 comparison versus sirolimus eluting stent - summary of results . . . . . . . . . . 15
2 Details for comparison versus bare-metal stent 292.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
3 Details for comparison versus paclitaxel eluting stent 533.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
4 Details for comparison versus sirolimus eluting stent 664.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 664.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
5 Ongoing studies of Unparticular patients 755.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
II Diabetic patients 77
6 Overview of available evidence for diabetic patients 796.1 Main results for Diabetic patients . . . . . . . . . . . . . . . . . . . . . . . . . . . 836.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 836.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 836.4 comparison versus rapamycin eluting stent - summary of results . . . . . . . . . 83
7 Details for comparison versus bare-metal stent 927.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 927.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
8 Details for comparison versus paclitaxel eluting stent 1038.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1038.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
9 Details for comparison versus rapamycin eluting stent 1109.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1109.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
10 Ongoing studies of Diabetic patients 11310.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
4 CONTENTS
III Acute myocardial infarction 115
11 Overview of available evidence for acute myocardial infarction 11711.1 Main results for Acute myocardial infarction . . . . . . . . . . . . . . . . . . . . . 12011.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 12011.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 120
12 Details for comparison versus bare-metal stent 12912.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12912.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
13 Details for comparison versus paclitaxel eluting stent 14013.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14013.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142
14 Ongoing studies of Acute myocardial infarction 14714.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
IV Small vessels 149
15 Overview of available evidence for small vessels 15115.1 Main results for small vessels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15415.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 15415.3 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 154
16 Details for comparison versus bare-metal stent 16016.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16016.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
17 Details for comparison versus paclitaxel eluting stent 16617.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16617.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
18 Ongoing studies of small vessels 17318.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
V Long or complex lesion 175
19 Overview of available evidence for long or complex lesion 17719.1 Main results for long or complex lesion . . . . . . . . . . . . . . . . . . . . . . . . 18119.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 18119.3 comparison versus CABG - summary of results . . . . . . . . . . . . . . . . . . . 18119.4 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 181
20 Details for comparison versus bare-metal stent 18920.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18920.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
21 Details for comparison versus CABG 19721.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19721.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
CONTENTS 5
22 Details for comparison versus paclitaxel eluting stent 20222.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20222.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204
23 Ongoing studies of long or complex lesion 21123.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
VI In-stent restenosis 213
24 Overview of available evidence for in-stent restenosis 21524.1 Main results for in-stent restenosis . . . . . . . . . . . . . . . . . . . . . . . . . . 21924.2 comparison versus ballon angioplasty - summary of results . . . . . . . . . . . . 21924.3 comparison versus brachytherapy - summary of results . . . . . . . . . . . . . . 21924.4 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 219
25 Details for comparison versus ballon angioplasty 22525.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22525.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
26 Details for comparison versus brachytherapy 23026.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23026.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
27 Details for comparison versus paclitaxel eluting stent 23627.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23627.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
28 Ongoing studies of in-stent restenosis 24128.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
VII Bypass graft lesions 243
29 Overview of available evidence for bypass graft lesions 24529.1 Main results for bypass graft lesions . . . . . . . . . . . . . . . . . . . . . . . . . 24729.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 247
30 Details for comparison versus bare-metal stent 25130.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25130.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
31 Ongoing studies of bypass graft lesions 25731.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
VIII Unprotected left main coronary artery stenosis 259
32 Overview of available evidence for unprotected left main coronary arterystenosis 26132.1 Main results for unprotected left main coronary artery stenosis . . . . . . . . . . 26332.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 263
6 CONTENTS
33 Details for comparison versus bare-metal stent 26633.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26633.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
34 Ongoing studies of unprotected left main coronary artery stenosis 27134.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
IX Total occlusion 273
35 Overview of available evidence for total occlusion 27535.1 Main results for total occlusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27735.2 comparison versus bare-metal stent - summary of results . . . . . . . . . . . . . 277
36 Details for comparison versus bare-metal stent 28036.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28036.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
37 Ongoing studies of total occlusion 28737.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
X Bifurcation 289
38 Overview of available evidence for bifurcation 29138.1 Main results for bifurcation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29338.2 comparison versus paclitaxel eluting stent - summary of results . . . . . . . . . . 293
39 Details for comparison versus paclitaxel eluting stent 29539.1 Available RCTs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29539.2 Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
40 Ongoing studies of bifurcation 29940.1 List of ongoing trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
Part I
Unparticular patients
7
8
9
1 Overview of available evidence for unparticular
patients
A total of 34 RCTs which randomized 19365 patients were identified. (see tables 1.1 to 1.3 )In all, 22 reports concerned comparison versus bare-metal stent , 10 the comparison versus
paclitaxel eluting stent and 2 the comparison versus sirolimus eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 2 (page 29)
for comparison versus bare-metal stent, in section 3 (page 53 ) for comparison versus paclitaxeleluting stent and in section 4 (page 66 ) for comparison versus sirolimus eluting stent.
The average study size was 605 patients per arm (range 15 to 1065 per arm). The first studywas published in 2002, and the last study was published in 2008. 10 trials were double blindand 14 were open-label in design. All included studies were reported in English language. Wefound one unpublished trial.
10CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Table
1.1
:M
ain
study
chara
cter
isti
cs-
Unpar
ticu
lar
pat
ients
-co
mpar
ison
vers
us
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Dactinom
ycin
elu
ting
stentvers
us
bare
-meta
lst
ent
AC
TIO
N,
2004
[1,
2]
Mult
ilin
kT
etra
sten
tvs.
unco
ate
dM
ult
ilin
kT
etra
sten
t
241
vs.
119
single
-blind
Para
llel
gro
ups
majo
radver
seca
rdia
cev
ents
at
30d
worl
dw
ide
Evero
lim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
SP
IRIT
III,
2008
[3,
4]
XIE
NC
EV
vs.
Taxus
669
vs.
333
single
-blind
Para
llel
gro
ups
in-s
egm
ent
late
loss
US
FU
TU
RE
II,
2006
[5,
6,
7]
unpublish
ed
CH
AM
PIO
Nvs.
bare
-met
al
sten
t43
vs.
21
double
-blind
Para
llel
gro
ups
angio
gra
phic
late
loss
at
6m
onth
sN
A
FU
TU
RE
I,2004
[8]
ever
olim
us
coate
dS-S
tent
vs.
S-S
tent
27
vs.
15
single
-blind
Para
llel
gro
ups
MA
CE
Ger
many
SP
IRIT
I,0
[9,
10,
11]
unpublish
ed
XIE
NC
Evs.
MU
LT
I-L
INK
VIS
ION
28
vs.
32
single
-blind
Para
llel
gro
ups
in-s
tent
late
loss
NA
SP
IRIT
II,
0[]
unpublish
edX
IEN
CE
Vvs.
TA
XU
SE
XP
RE
SS2
223
vs.
77
single
-blind
(pati
ent)
Para
llel
gro
ups
In-s
tent
late
loss
NA
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
SC
OR
E,
2004
[12,
13]
QuaD
DS
sten
ts(p
acl
itaxel
)vs.
unco
ate
dco
ntr
ol
sten
ts
126
vs.
140
op
enP
ara
llel
gro
ups
none
Worl
dw
ide
TA
XU
SIV
,2004
[14]
TA
XU
Svs.
EX
PR
ESS
662
vs.
652
double
-blind
Para
llel
gro
ups
TV
RU
nit
edSta
tes
TA
XU
SI,
2003
[15]
TA
XU
SN
IRvs.
NIR
sten
t31
vs.
30
double
-blind
Para
llel
gro
ups
Com
bin
ati
on
of
dea
th,A
MI,
TV
R,
sten
tth
rom
bosi
s
Ger
many
TA
XU
SII
,2003
[16]
TA
XU
Svs.
NIR
sten
t266
vs.
270
double
-blind
Para
llel
gro
ups
Neo
inti
mal
pro
life
rati
on
Glo
bal
Paclita
xel,
non-p
oly
meri
celu
ting
stentvers
us
bare
-meta
lst
ent
cont
inue
d...
11
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gdesi
gn
Pri
mary
Endp
oin
tL
ocalisa
tion
DE
LIV
ER
,2004
[17,
18,
19]
non-p
oly
mer
-base
dpacl
itaxel
-coate
dA
CH
IEV
Est
ent
vs.
stain
less
stee
lM
ult
i-L
ink
(ML
)P
EN
TA
sten
t
524
vs.
519
single
-blind
Para
llel
gro
ups
targ
et-v
esse
lfa
ilure
US
EL
UT
ES,
2004
[20]
coate
dV
-Fle
xP
lus
vs.
V-F
lex
Plu
s152
vs.
38
op
enP
ara
llel
gro
ups
per
cent
dia
met
erst
enosi
sE
uro
pe
ASP
EC
T,
2003
[21]
coate
dSupra
-Gst
ent
vs.
Supra
-Gst
ent
117
vs.
58
double
-blind
Para
llel
gro
ups
sten
osi
sp
erce
nta
ge
NA
PA
TE
NC
Y,
2002
[22]
Logic
PT
Xpacl
itaxel
Elu
ting
Coro
nary
Ste
nts
vs.
unco
ate
dco
ntr
ol
sten
ts
24
vs.
26
double
blind
Para
llel
gro
ups
NA
NA
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
Ort
ola
ni
etal,
2007
[23]
Cypher
vs.
Vis
ion
NA
vs.
NA
single
-blind
Para
llel
gro
ups
Late
lum
enlo
ssN
A
Koch
iadakis
,2007
[24]
siro
lim
us-
eluti
ng
sten
tsvs.
bare
met
al
sten
t38
vs.
43
op
enP
ara
llel
gro
ups
inflam
mato
ryre
sponse
Gre
ece
Pach
eet
al,
2005
[25]
Cypher
vs.
BeS
tent
2250
vs.
250
op
enP
ara
llel
gro
ups
Bin
ary
rest
enosi
sG
erm
any
C-S
IRIU
S,
2004
[26]
coate
dB
x-V
EL
OC
ITY
vs.
Bx-V
EL
OC
ITY
50
vs.
50
double
-blind
Para
llel
gro
ups
Min
imal
lum
endia
met
erC
anada
SIR
IUS,
2003
[27,
28]
SE
Svs.
Bx
Vel
oci
ty533
vs.
525
double
-blind
Para
llel
gro
ups
Com
bin
ati
on
of
card
iacd
eath
,A
MI,
TV
R
Unit
edSta
tes
E-S
IRIU
S,
2003
[29]
coate
dB
xV
eloci
tyvs.
Bx
Vel
oci
ty175
vs.
177
op
enP
ara
llel
gro
ups
Min
imal
lum
endia
met
erE
uro
pe
RA
VE
L,
2002
[30,
31]
coate
dB
xV
eloci
tyvs.
Bx
Vel
oci
ty120
vs.
118
double
-blind
Para
llel
gro
ups
Late
lum
enlo
ssG
lobal
Zota
rolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
EN
DE
AV
OR
II,
2006
[32,
33,
34,
35]
AV
EZ
ota
rolim
us-
Elu
ting
Dri
ver
vs.
Dri
ver
598
vs.
599
double
-blind
Para
llel
gro
ups
targ
etves
sel
failure
worl
dw
ide
12CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Table
1.2
:M
ain
study
char
act
eris
tics
-U
npar
ticu
lar
pat
ients
-co
mpar
ison
vers
us
pacl
itaxel
eluti
ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
paclita
xel
elu
ting
stent
CoSta
rst
entvers
us
paclita
xelelu
ting
stent
Cost
ar
II,
2008
[1]
CoSta
rst
ent
(Conor
Med
Syst
ems)
vs.
Taxus
(Bost
on
Sci
enti
fic)
989
vs.
686
single
-blind
Para
llel
gro
ups
MA
CE
US,
Ger
many,
Bel
giu
m,
and
New
Zea
land
Rapam
ycin
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Wes
sely
,2008
[2]
rapam
yci
np
oly
mer
-coate
ddru
g-e
luti
ng
sten
tvs.
pacl
itaxel
poly
mer
-coate
ddru
g-e
luti
ng
sten
t
NA
vs.
NA
NA
Para
llel
gro
ups
none
Ger
many
ISA
R-T
EST
-1,
2006
[3]
rapam
yci
n-e
luti
ng
sten
tY
ukon
vs.
Taxus
225
vs.
225
op
enP
ara
llel
gro
ups
in-s
tent
late
lum
enlo
ssG
erm
any
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
SO
RT
OU
TII
,2008
[4,
5]
Cypher
sten
tvs.
Taxus
sten
t(B
ost
on
Sci
enti
fic
Corp
)
1065
vs.
1033
op
enP
ara
llel
gro
ups
majo
radver
seca
rdia
cev
ents
Den
mark
.
Han,
2006
[6]
Cypher
vs.
Taxus
210
vs.
206
op
enP
ara
llel
gro
ups
none
Chin
a
Zhang
(SE
Svs
PE
S),
2006
[7]
Cypher
vs.
Taxus
246
vs.
203
op
enP
ara
llel
gro
ups
dea
th,A
MI,
TV
Rat
30day
sC
hin
a
RE
AL
ITY
,2006
[8]
Cypher
vs.
Taxus
701
vs.
685
op
enP
ara
llel
gro
ups
Bin
ary
rest
enosi
sE
uro
pe,
Lati
nA
mer
ica,
and
Asi
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SIR
TA
X(W
indec
ker
),2005
[9]
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vs.
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503
vs.
509
single
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Para
llel
gro
ups
card
iac
dea
th,
AM
I,T
LR
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TA
Xi,
2005
[10,
11]
Cypher
vs.
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102
vs.
100
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SK
ET
(vs
pacl
itaxel
),2005
[12]
Cypher
vs.
Taxus
264
vs.
281
op
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ups
cost
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ecti
ven
ess
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13
Table
1.3
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ain
study
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stent
Bio
lim
us
elu
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stentvers
us
siro
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us
elu
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AD
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2008
[1]
Bio
Matr
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elu
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DE
AV
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III,
2006
[2,
3]
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vs.
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S
14CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
1.1 Main results for Unparticular patients
The meta-analysis of the available trials provide the results listed in tables 1.4 to 1.6 (page 15)and in the following graphs.
1.2 comparison versus bare-metal stent - summary of results
Dactinomycin eluting stent was superior to bare-metal stent in terms of MACE (RR=0.07,95% CI 0.04 to 0.11, p=0.0000, 1 trial) and CABG (RR=0.09, 95% CI 0.01 to 0.74, p=0.0250,1 trial) .However, no significant difference was found on all cause death (RR=0.44, 95% CI 0.03to 6.89, p=0.5549, 1 trial) , MI (fatal and non fatal) (RR=2.61, 95% CI 0.32 to 21.42, p=0.3714,1 trial) and target lesion revascularisation (RR=0.26, 95% CI 0.06 to 1.07, p=0.0624, 1 trial) .
Everolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.55,95% CI 0.37 to 0.82, p=0.0031, 4 trials) and target lesion revascularisation (RR=0.53, 95% CI0.31 to 0.91, p=0.0210, 4 trials) .However, no significant difference was found on all cause death(RR=1.00, 95% CI 0.34 to 2.96, p=0.9929, 3 trials) , cardiac death (RR=0.65, 95% CI 0.17 to2.40, p=0.5149, 2 trials) , MI (fatal and non fatal) (RR=0.66, 95% CI 0.34 to 1.26, p=0.2057,3 trials) and CABG (RR=0.35, 95% CI 0.01 to 17.25, p=0.5941, 1 trial) .
Paclitaxel eluting stent was superior to bare-metal stent in terms of target lesionrevascularisation (RR=0.27, 95% CI 0.19 to 0.40, p=0.0000, 3 trials) , in-lesion binary restenosis(RR=0.30, 95% CI 0.19 to 0.47, p=0.0000, 1 trial) and angiographic restenosis (RR=0.23, 95%CI 0.18 to 0.30, p=0.0000, 1 trial) .But paclitaxel eluting stent increased the risk of MI (fataland non fatal) (RR=2.77, 95% CI 1.06 to 7.21, p=0.0374, 4 trials) .However, no significantdifference was found on all cause death (RR=1.23, 95% CI 0.50 to 3.02, p=0.6560, 4 trials) ,cardiac death (RR=2.41, 95% CI 0.35 to 16.71, p=0.3745, 2 trials) , MACE (RR=0.66, 95%CI 0.40 to 1.07, p=0.0934, 4 trials) with a random effect model in reason of a heterogeneity(Het. p=0.0081) and target-vessel revascularization (RR=0.57, 95% CI 0.27 to 1.21, p=0.1422,2 trials) with a random effect model in reason of a heterogeneity (Het. p=0.0144) .
No significant difference was found between paclitaxel, non-polymeric eluting stentand bare-metal stent in terms of all cause death (RR=0.42, 95% CI 0.10 to 1.81, p=0.2461,4 trials) , MI (fatal and non fatal) (RR=0.97, 95% CI 0.19 to 4.99, p=0.9689, 4 trials) , MACE(RR=0.74, 95% CI 0.52 to 1.05, p=0.0958, 4 trials) and target lesion revascularisation (RR=0.42,95% CI 0.10 to 1.81, p=0.2461, 4 trials) .
Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.38,95% CI 0.26 to 0.55, p=0.0000, 5 trials) , target-vessel revascularization (RR=0.41, 95% CI 0.30to 0.57, p=0.0000, 1 trial) and target lesion revascularisation (RR=0.25, 95% CI 0.16 to 0.39,p=0.0000, 5 trials) .However, no significant difference was found on all cause death (RR=1.42,95% CI 0.67 to 3.01, p=0.3585, 5 trials) , MI (fatal and non fatal) (RR=0.98, 95% CI 0.58 to1.66, p=0.9480, 4 trials) and CABG (RR=0.46, 95% CI 0.16 to 1.30, p=0.1426, 4 trials) .
Zotarolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.50,95% CI 0.36 to 0.71, p=0.0000, 1 trial) and angiographic restenosis (RR=0.39, 95% CI 0.28 to0.55, p=0.0000, 1 trial) .
1.3 comparison versus paclitaxel eluting stent - summary ofresults
CoStar stent was inferior to paclitaxel eluting stent in terms of MACE (RR=1.61, 95% CI1.16 to 2.23, p=0.0045, 1 trial) and target-vessel revascularization (RR=1.91, 95% CI 1.27 to
1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS15
2.89, p=0.0021, 1 trial) . No significant difference was found on all cause death (RR=0.69, 95%CI 0.20 to 2.39, p=0.5618, 1 trial) and MI (fatal and non fatal) (RR=1.47, 95% CI 0.82 to 2.65,p=0.1946, 1 trial) .
No significant difference was found between rapamycin eluting stent and paclitaxeleluting stent in terms of all cause death (RR=0.67, 95% CI 0.11 to 3.95, p=0.6552, 1 trial) .
No significant difference was found between sirolimus eluting stent and paclitaxel elut-ing stent in terms of all cause death (RR=0.98, 95% CI 0.64 to 1.50, p=0.9272, 7 trials) , cardiacdeath (RR=0.85, 95% CI 0.34 to 2.12, p=0.7231, 3 trials) , MI (fatal and non fatal) (RR=0.79,95% CI 0.59 to 1.07, p=0.1298, 7 trials) , MACE (RR=0.77, 95% CI 0.59 to 1.01, p=0.0587,4 trials) , target-vessel revascularization (RR=0.75, 95% CI 0.51 to 1.09, p=0.1319, 3 trials), target lesion revascularisation (RR=0.84, 95% CI 0.65 to 1.07, p=0.1531, 7 trials) , CABG(RR=1.96, 95% CI 0.07 to 57.80, p=0.6965, 1 trial) , in-lesion binary restenosis (RR=0.88, 95%CI 0.67 to 1.16, p=0.3591, 1 trial) and angiographic restenosis (RR=0.86, 95% CI 0.62 to 1.19,p=0.3692, 1 trial) .
1.4 comparison versus sirolimus eluting stent - summary ofresults
No significant difference was found between biolimus eluting stent and sirolimus elutingstent in terms of all cause death (RR=0.91, 95% CI 0.51 to 1.61, p=0.7437, 1 trial) , cardiacdeath (RR=0.66, 95% CI 0.34 to 1.29, p=0.2259, 1 trial) , MI (fatal and non fatal) (RR=1.25,95% CI 0.83 to 1.88, p=0.2925, 1 trial) , MACE (RR=0.92, 95% CI 0.69 to 1.23, p=0.5822, 1trial) , target-vessel revascularization (RR=0.80, 95% CI 0.53 to 1.22, p=0.2994, 1 trial) , targetlesion revascularisation (RR=0.87, 95% CI 0.57 to 1.35, p=0.5400, 1 trial) , CABG (RR=0.50,95% CI 0.20 to 1.22, p=0.1276, 1 trial) and angiographic restenosis (RR=0.64, 95% CI 0.33 to1.24, p=0.1833, 1 trial) .
Zotarolimus eluting stent was superior to sirolimus eluting stent in terms of MI (fataland non fatal) (RR=0.18, 95% CI 0.03 to 0.96, p=0.0451, 1 trial) .But zotarolimus eluting stentincreased the risk of in-lesion binary restenosis (RR=2.75, 95% CI 1.00 to 7.56, p=0.0499, 1trial) and angiographic restenosis (RR=4.33, 95% CI 1.05 to 17.91, p=0.0429, 1 trial) .How-ever, no significant difference was found on all cause death (RR=0.70, 95% CI 0.06 to 7.65,p=0.7700, 1 trial) , MACE (RR=0.97, 95% CI 0.47 to 2.02, p=0.9398, 1 trial) and target lesionrevascularisation (RR=1.84, 95% CI 0.64 to 5.24, p=0.2549, 1 trial) .
Table 1.4: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Dactinomycin eluting stent versus bare-metal stent
All cause death RR=0.44 0.03;6.89 0.5549 1.0000 (0.00) 1 343
MI (fatal and non fatal) RR=2.61 0.32;21.42 0.3714 1.0000 (0.00) 1 343
MACE RR=0.07 0.04;0.11 0.0000 1.0000 (0.00) 1 343
target lesion revascularisation RR=0.26 0.06;1.07 0.0624 1.0000 (0.00) 1 343
CABG RR=0.09 0.01;0.74 0.0250 1.0000 (0.00) 1 343
Everolimus eluting stent versus bare-metal stent
All cause death RR=1.00 0.34;2.96 0.9929 0.9953 (0.00) 3 1078
cardiac death RR=0.65 0.17;2.40 0.5149 0.4069 (0.00) 2 1276
MI (fatal and non fatal) RR=0.66 0.34;1.26 0.2057 0.6190 (0.00) 3 1333
continued...
16CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Endpoint Effect 95% CI p ass p het k n
MACE RR=0.55 0.37;0.82 0.0031 0.8420 (0.00) 4 1373
target lesion revascularisation RR=0.53 0.31;0.91 0.0210 0.7667 (0.00) 4 1378
CABG RR=0.35 0.01;17.25 0.5941 1.0000 (0.00) 1 300
Stent thrombosis (any, end offollow up)
RR=1.21 0.27;5.47 0.8023 0.9743 (0.00) 2 1024
4y stent thrombosis (ARC) RR=1.35 0.43;4.19 0.6088 1.0000 (0.00) 1 971
Acute stent thrombosis(<=24h)
RR=0.35 0.01;17.25 0.5941 1.0000 (0.00) 1 300
sub acute stent thrombosis(1-30 days)
RR=0.35 0.01;17.25 0.5941 1.0000 (0.00) 1 300
late stent thrombosis (31days -1year)
RR=0.35 0.02;5.45 0.4501 1.0000 (0.00) 1 300
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=1.23 0.50;3.02 0.6560 0.3792 (0.03) 4 2137
cardiac death RR=2.41 0.35;16.71 0.3745 0.1648 (0.48) 2 1580
MI (fatal and non fatal) RR=2.77 1.06;7.21 0.0374 0.6839 (0.00) 4 2137
MACE RR=0.66 0.40;1.07 0.0934 0.0081 (0.75) 4 2164
target-vessel revascularization RR=0.57 0.27;1.21 0.1422 0.0144 (0.83) 2 1580
target lesion revascularisation RR=0.27 0.19;0.40 0.0000 0.9151 (0.00) 3 1898
in-lesion binary restenosis RR=0.30 0.19;0.47 0.0000 1.0000 (0.00) 1 1314
Stent thrombosis (any, end offollow up)
RR=3.27 0.55;19.33 0.1920 0.0666 (0.58) 4 2137
sub acute stent thrombosis(1-30 days)
RR=0.98 0.14;6.91 0.9838 1.0000 (0.00) 1 1314
late stent thrombosis (31days -1year)
RR=2.02 0.76;5.37 0.1563 0.8457 (0.00) 3 1911
angiographic restenosis RR=0.23 0.18;0.30 0.0000 1.0000 (0.00) 1 559
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
All cause death RR=0.42 0.10;1.81 0.2461 0.9168 (0.00) 4 1446
MI (fatal and non fatal) RR=0.97 0.19;4.99 0.9689 0.8212 (0.00) 4 1446
MACE RR=0.74 0.52;1.05 0.0958 0.4882 (0.00) 4 1444
target lesion revascularisation RR=0.42 0.10;1.81 0.2461 0.9168 (0.00) 4 1446
Stent thrombosis (any, end offollow up)
RR=0.97 0.26;3.61 0.9620 0.6062 (0.00) 4 1446
late stent thrombosis (31days -1year)
RR=0.57 0.08;4.00 0.5684 0.8414 (0.00) 3 1398
Sirolimus eluting stent versus bare-metal stent
All cause death RR=1.42 0.67;3.01 0.3585 0.9903 (0.00) 5 2248
MI (fatal and non fatal) RR=0.98 0.58;1.66 0.9480 0.5757 (0.00) 4 1748
MACE RR=0.38 0.26;0.55 0.0000 0.0741 (0.53) 5 2248
target-vessel revascularization RR=0.41 0.30;0.57 0.0000 1.0000 (0.00) 1 1058
target lesion revascularisation RR=0.25 0.16;0.39 0.0000 0.1772 (0.37) 5 2248
CABG RR=0.46 0.16;1.30 0.1426 0.6684 (0.00) 4 1748
Stent thrombosis (any, end offollow up)
RR=0.86 0.25;2.95 0.8044 0.7065 (0.00) 4 1748
late stent thrombosis (31days -1year)
RR=0.51 0.11;2.41 0.3950 0.9460 (0.00) 4 1748
Zotarolimus eluting stent versus bare-metal stent
MACE RR=0.50 0.36;0.71 0.0000 1.0000 (0.00) 1 1197
Stent thrombosis (any, end offollow up)
RR=0.43 0.11;1.65 0.2188 1.0000 (0.00) 1 1197
continued...
1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS17
Endpoint Effect 95% CI p ass p het k n
angiographic restenosis RR=0.39 0.28;0.55 0.0000 1.0000 (0.00) 1 600
Table 1.5: Summary of all results for comparison versus paclitaxel eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
CoStar stent versus paclitaxel eluting stent
All cause death RR=0.69 0.20;2.39 0.5618 1.0000 (0.00) 1 1675
MI (fatal and non fatal) RR=1.47 0.82;2.65 0.1946 1.0000 (0.00) 1 1675
MACE RR=1.61 1.16;2.23 0.0045 1.0000 (1.00) 1 1675
target-vessel revascularization RR=1.91 1.27;2.89 0.0021 1.0000 (0.00) 1 1675
Stent thrombosis (any, end offollow up)
RR=4.16 0.50;34.49 0.1863 1.0000 (0.00) 1 1675
late stent thrombosis (31days -1year)
RR=0.69 0.04;11.07 0.7958 1.0000 (0.00) 1 1675
Rapamycin eluting stent versus paclitaxel eluting stent
All cause death RR=0.67 0.11;3.95 0.6552 1.0000 (0.00) 1 450
Stent thrombosis (any, end offollow up)
RR=2.00 0.18;21.90 0.5703 1.0000 (0.00) 1 450
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.98 0.64;1.50 0.9272 0.6672 (0.00) 7 6075
cardiac death RR=0.85 0.34;2.12 0.7231 0.2939 (0.18) 3 4463
MI (fatal and non fatal) RR=0.79 0.59;1.07 0.1298 0.9989 (0.00) 7 6075
MACE RR=0.77 0.59;1.01 0.0587 0.3111 (0.16) 4 4875
target-vessel revascularization RR=0.75 0.51;1.09 0.1319 0.4456 (0.00) 3 4463
target lesion revascularisation RR=0.84 0.65;1.07 0.1531 0.6239 (0.00) 7 6075
CABG RR=1.96 0.07;57.80 0.6965 1.0000 (0.00) 1 202
in-lesion binary restenosis RR=0.88 0.67;1.16 0.3591 1.0000 (0.00) 1 1911
Stent thrombosis (any, end offollow up)
RR=0.82 0.57;1.20 0.3108 0.6992 (0.00) 7 6038
4y stent thrombosis (ARC) RR=0.73 0.49;1.06 0.0995 0.6547 (0.00) 7 6075
Acute stent thrombosis(<=24h)
RR=0.49 0.09;2.66 0.4079 1.0000 (0.00) 1 1353
sub acute stent thrombosis(1-30 days)
RR=0.42 0.11;1.61 0.2063 1.0000 (0.00) 1 1353
late stent thrombosis (31days -1year)
RR=0.24 0.01;5.41 0.3728 1.0000 (0.00) 1 1353
angiographic restenosis RR=0.86 0.62;1.19 0.3692 1.0000 (0.00) 1 1911
Table 1.6: Summary of all results for comparison versus sirolimus eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Biolimus eluting stent versus sirolimus eluting stent
All cause death RR=0.91 0.51;1.61 0.7437 1.0000 (0.00) 1 1707
cardiac death RR=0.66 0.34;1.29 0.2259 1.0000 (0.00) 1 1707
MI (fatal and non fatal) RR=1.25 0.83;1.88 0.2925 1.0000 (0.00) 1 1707
MACE RR=0.92 0.69;1.23 0.5822 1.0000 (0.00) 1 1707
target-vessel revascularization RR=0.80 0.53;1.22 0.2994 1.0000 (0.00) 1 1707
target lesion revascularisation RR=0.87 0.57;1.35 0.5400 1.0000 (0.00) 1 1707
CABG RR=0.50 0.20;1.22 0.1276 1.0000 (0.00) 1 1707
continued...
18CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Endpoint Effect 95% CI p ass p het k n
Stent thrombosis (any, end offollow up)
RR=1.15 0.63;2.11 0.6547 1.0000 (0.00) 1 1707
late stent thrombosis (31days -1year)
RR=0.99 0.25;3.95 0.9907 1.0000 (0.00) 1 1707
angiographic restenosis RR=0.64 0.33;1.24 0.1833 1.0000 (0.00) 1 484
Zotarolimus eluting stent versus sirolimus eluting stent
All cause death RR=0.70 0.06;7.65 0.7700 1.0000 (0.00) 1 432
MI (fatal and non fatal) RR=0.18 0.03;0.96 0.0451 1.0000 (0.00) 1 429
MACE RR=0.97 0.47;2.02 0.9398 1.0000 (0.00) 1 432
target lesion revascularisation RR=1.84 0.64;5.24 0.2549 1.0000 (1.00) 1 432
in-lesion binary restenosis RR=2.75 1.00;7.56 0.0499 1.0000 (0.00) 1 376
Stent thrombosis (any, end offollow up)
RR=0.35 0.01;17.54 0.5991 1.0000 (0.00) 1 432
angiographic restenosis RR=4.33 1.05;17.91 0.0429 1.0000 (0.00) 1 376
Figure 1.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Dactinomycin eluting stent versus bare-metal stent
0.44 [0.03;6.89] .55 1 343 1.00 0.00
Everolimus eluting stent versus bare-metal stent
1.00 [0.34;2.96] .99 3 1078 1.00 0.00
Paclitaxel eluting stent versus bare-metalstent
1.23 [0.50;3.02] .66 4 2137 .38 0.03
Paclitaxel, non-polymeric eluting stentversus bare-metal stent
0.42 [0.10;1.81] .25 4 1446 .92 0.00
Sirolimus eluting stent versus bare-metalstent
1.42 [0.67;3.01] .36 5 2248 .99 0.00
comparison versus paclitaxel eluting stent
CoStar stent versus paclitaxel elutingstent
0.69 [0.20;2.39] .56 1 1675 1.00 0.00
Rapamycin eluting stent versus pacli-taxel eluting stent
0.67 [0.11;3.95] .66 1 450 1.00 0.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.98 [0.64;1.50] .93 7 6075 .67 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.91 [0.51;1.61] .74 1 1707 1.00 0.00
Zotarolimus eluting stent versussirolimus eluting stent
0.70 [0.06;7.65] .77 1 432 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS19
Figure 1.2: Forest’s plot for cardiac death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Everolimus eluting stent versus bare-metal stent
0.65 [0.17;2.40] .51 2 1276 .41 0.00
Paclitaxel eluting stent versus bare-metalstent
2.41 [0.35;16.71] .37 2 1580 .16 0.48
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.85 [0.34;2.12] .72 3 4463 .29 0.18
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.66 [0.34;1.29] .23 1 1707 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
20CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Figure 1.3: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Dactinomycin eluting stent versus bare-metal stent
2.61 [0.32;21.42] .37 1 343 1.00 0.00
Everolimus eluting stent versus bare-metal stent
0.66 [0.34;1.26] .21 3 1333 .62 0.00
Paclitaxel eluting stent versus bare-metalstent
2.77 [1.06;7.21] .04 4 2137 .68 0.00
Paclitaxel, non-polymeric eluting stentversus bare-metal stent
0.97 [0.19;4.99] .97 4 1446 .82 0.00
Sirolimus eluting stent versus bare-metalstent
0.98 [0.58;1.66] .95 4 1748 .58 0.00
comparison versus paclitaxel eluting stent
CoStar stent versus paclitaxel elutingstent
1.47 [0.82;2.65] .19 1 1675 1.00 0.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.79 [0.59;1.07] .13 7 6075 1.00 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
1.25 [0.83;1.88] .29 1 1707 1.00 0.00
Zotarolimus eluting stent versussirolimus eluting stent
0.18 [0.03;0.96] .05 1 429 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS21
Figure 1.4: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Dactinomycin eluting stent versus bare-metal stent
0.07 [0.04;0.11] .00 1 343 1.00 0.00
Everolimus eluting stent versus bare-metal stent
0.55 [0.37;0.82] .00 4 1373 .84 0.00
Paclitaxel eluting stent versus bare-metalstent
0.66 [0.40;1.07] .09 4 2164 .01 0.75
Paclitaxel, non-polymeric eluting stentversus bare-metal stent
0.74 [0.52;1.05] .10 4 1444 .49 0.00
Sirolimus eluting stent versus bare-metalstent
0.38 [0.26;0.55] .00 5 2248 .07 0.53
Zotarolimus eluting stent versus bare-metal stent
0.50 [0.36;0.71] .00 1 1197 1.00 0.00
comparison versus paclitaxel eluting stent
CoStar stent versus paclitaxel elutingstent
1.61 [1.16;2.23] .00 1 1675 1.00 1.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.77 [0.59;1.01] .06 4 4875 .31 0.16
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.92 [0.69;1.23] .58 1 1707 1.00 0.00
Zotarolimus eluting stent versussirolimus eluting stent
0.97 [0.47;2.02] .94 1 432 1.00 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
22CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Figure 1.5: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.57 [0.27;1.21] .14 2 1580 .01 0.83
Sirolimus eluting stent versus bare-metalstent
0.41 [0.30;0.57] .00 1 1058 1.00 0.00
comparison versus paclitaxel eluting stent
CoStar stent versus paclitaxel elutingstent
1.91 [1.27;2.89] .00 1 1675 1.00 0.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.75 [0.51;1.09] .13 3 4463 .45 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.80 [0.53;1.22] .30 1 1707 1.00 0.00
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS23
Figure 1.6: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Dactinomycin eluting stent versus bare-metal stent
0.26 [0.06;1.07] .06 1 343 1.00 0.00
Everolimus eluting stent versus bare-metal stent
0.53 [0.31;0.91] .02 4 1378 .77 0.00
Paclitaxel eluting stent versus bare-metalstent
0.27 [0.19;0.40] .00 3 1898 .92 0.00
Paclitaxel, non-polymeric eluting stentversus bare-metal stent
0.42 [0.10;1.81] .25 4 1446 .92 0.00
Sirolimus eluting stent versus bare-metalstent
0.25 [0.16;0.39] .00 5 2248 .18 0.37
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.84 [0.65;1.07] .15 7 6075 .62 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.87 [0.57;1.35] .54 1 1707 1.00 0.00
Zotarolimus eluting stent versussirolimus eluting stent
1.84 [0.64;5.24] .25 1 432 1.00 1.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
24CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Figure 1.7: Forest’s plot for CABG
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Dactinomycin eluting stent versus bare-metal stent
0.09 [0.01;0.74] .03 1 343 1.00 0.00
Everolimus eluting stent versus bare-metal stent
0.35 [0.01;17.25] .59 1 300 1.00 0.00
Sirolimus eluting stent versus bare-metalstent
0.46 [0.16;1.30] .14 4 1748 .67 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
1.96 [0.07;57.80] .70 1 202 1.00 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.50 [0.20;1.22] .13 1 1707 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 1.8: Forest’s plot for in-lesion binary restenosis
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.30 [0.19;0.47] .00 1 1314 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.88 [0.67;1.16] .36 1 1911 1.00 0.00
comparison versus sirolimus eluting stent
Zotarolimus eluting stent versussirolimus eluting stent
2.75 [1.00;7.56] .05 1 376 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS25
Figure 1.9: Forest’s plot for stent thrombosis (any, end of follow up)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Everolimus eluting stent versus bare-metal stent
1.21 [0.27;5.47] .80 2 1024 .97 0.00
Paclitaxel eluting stent versus bare-metalstent
3.27 [0.55;19.33] .19 4 2137 .07 0.58
Paclitaxel, non-polymeric eluting stentversus bare-metal stent
0.97 [0.26;3.61] .96 4 1446 .61 0.00
Sirolimus eluting stent versus bare-metalstent
0.86 [0.25;2.95] .80 4 1748 .71 0.00
Zotarolimus eluting stent versus bare-metal stent
0.43 [0.11;1.65] .22 1 1197 1.00 0.00
comparison versus paclitaxel eluting stent
CoStar stent versus paclitaxel elutingstent
4.16 [0.50;34.49] .19 1 1675 1.00 0.00
Rapamycin eluting stent versus pacli-taxel eluting stent
2.00 [0.18;21.90] .57 1 450 1.00 0.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.82 [0.57;1.20] .31 7 6038 .70 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
1.15 [0.63;2.11] .65 1 1707 1.00 0.00
Zotarolimus eluting stent versussirolimus eluting stent
0.35 [0.01;17.54] .60 1 432 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
26CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Figure 1.10: Forest’s plot for 4y stent thrombosis (ARC)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Everolimus eluting stent versus bare-metal stent
1.35 [0.43;4.19] .61 1 971 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.73 [0.49;1.06] .10 7 6075 .65 0.00
comparison versus sirolimus eluting stent
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 1.11: Forest’s plot for acute stent thrombosis (<=24h)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Everolimus eluting stent versus bare-metal stent
0.35 [0.01;17.25] .59 1 300 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.49 [0.09;2.66] .41 1 1353 1.00 0.00
comparison versus sirolimus eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
1.4. COMPARISON VERSUS SIROLIMUS ELUTING STENT - SUMMARY OF RESULTS27
Figure 1.12: Forest’s plot for sub acute stent thrombosis (1-30 days)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Everolimus eluting stent versus bare-metal stent
0.35 [0.01;17.25] .59 1 300 1.00 0.00
Paclitaxel eluting stent versus bare-metalstent
0.98 [0.14;6.91] .98 1 1314 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.42 [0.11;1.61] .21 1 1353 1.00 0.00
comparison versus sirolimus eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 1.13: Forest’s plot for late stent thrombosis (31days - 1year)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Everolimus eluting stent versus bare-metal stent
0.35 [0.02;5.45] .45 1 300 1.00 0.00
Paclitaxel eluting stent versus bare-metalstent
2.02 [0.76;5.37] .16 3 1911 .85 0.00
Paclitaxel, non-polymeric eluting stentversus bare-metal stent
0.57 [0.08;4.00] .57 3 1398 .84 0.00
Sirolimus eluting stent versus bare-metalstent
0.51 [0.11;2.41] .40 4 1748 .95 0.00
comparison versus paclitaxel eluting stent
CoStar stent versus paclitaxel elutingstent
0.69 [0.04;11.07] .80 1 1675 1.00 0.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.24 [0.01;5.41] .37 1 1353 1.00 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.99 [0.25;3.95] .99 1 1707 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
28CHAPTER 1. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPARTICULAR PATIENTS
Figure 1.14: Forest’s plot for angiographic restenosis
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.23 [0.18;0.30] .00 1 559 1.00 0.00
Zotarolimus eluting stent versus bare-metal stent
0.39 [0.28;0.55] .00 1 600 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.86 [0.62;1.19] .37 1 1911 1.00 0.00
comparison versus sirolimus eluting stent
Biolimus eluting stent versus sirolimuseluting stent
0.64 [0.33;1.24] .18 1 484 1.00 0.00
Zotarolimus eluting stent versussirolimus eluting stent
4.33 [1.05;17.91] .04 1 376 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
29
2 Detailed results for comparison versus bare-metal
stent in unparticular patients
2.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
A total of 22 RCTs which randomized 8989 patients were identified: 1 trial compared dacti-nomycin eluting stent with bare-metal stent , 5 trials compared everolimus eluting stent withbare-metal stent , 4 trials compared paclitaxel eluting stent with bare-metal stent , 4 trials com-pared paclitaxel, non-polymeric eluting stent with bare-metal stent , 7 trials compared sirolimuseluting stent with bare-metal stent and 1 trial compared zotarolimus eluting stent with bare-metal stent (see 2.1 page 30).
The average study size was 428 patients per arm (range 15 to 669 per arm). The first studywas published in 2002, and the last study was published in 2008. 10 trials were double blindand 5 were open-label in design. All included studies were reported in English language. Wefound one unpublished trial.
MACE data was reported in 19 trials; 17 trials reported data on target lesion revascularisa-tion ; 17 trials reported data on All cause death; 16 trials reported data on MI (fatal and nonfatal); 13 trials reported data on angiographic restenosis ; 6 trials reported data on CABG; 3trials reported data on cardiac death; 2 trials reported data on target-vessel revascularization;15 trials reported data on Stent thrombosis (any, end of follow up); 11 trials reported data onlate stent thrombosis (31days - 1year); 1 trials reported data on sub acute stent thrombosis (1-30days); 1 trials reported data on Acute stent thrombosis (¡=24h); and 1 trials reported data on4y stent thrombosis (ARC).
Following table 2.1 (page 30) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus bare-metal stent.
30 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Table
2.1
:M
ain
study
char
act
eris
tics
-U
npar
ticu
lar
pat
ients
-co
mpari
son
vers
us
bare
-met
alst
ent
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Dactinom
ycin
elu
ting
stentvers
us
bare
-meta
lst
ent
AC
TIO
N,
2004
[1,
2]
n=
241
vs.
119
Pati
ents
wit
hst
able
angin
ap
ecto
ris
ors
ilen
tis
chem
iaand
asi
ngle
de
nov
ole
sion
ina
nati
vec
oro
nary
art
ery
>=
3.0
mm
and
<=
4.0
mm
india
met
erth
atc
ould
be
cover
edby
an
18-m
mst
ent
Mult
ilin
kT
etra
sten
tvs.
unco
ate
dM
ult
ilin
kT
etra
sten
tsi
ngle
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:m
ajo
radver
seca
rdia
cev
ents
at
30d
mult
icen
ter,
worl
dw
ide
QC
Afo
llow
-up
dura
tion:
681
Evero
lim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
SP
IRIT
III,
2008
[3,
4]
n=
669
vs.
333
lesi
ons
28
mm
or
less
inle
ngth
and
wit
hre
fere
nce
ves
sel
dia
met
erb
etw
een
2.5
and
3.7
5m
XIE
NC
EV
vs.
Taxus
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:in
-seg
men
tla
telo
ss65
centr
es,
US
FU
TU
RE
II,
2006
[5,
6,
7]
unpublish
edn
=43
vs.
21
Pati
ents
wit
hde
nov
ole
sions
inves
sels
wit
ha
refe
rence
dia
met
erof
2.7
5-4
.0m
mand
length
</=
18
mm
CH
AM
PIO
Nvs.
bare
-met
al
sten
tdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:angio
gra
phic
late
loss
at
6m
onth
sm
ult
icen
ter,
NA
QC
Afo
llow
-up
dura
tion:
686
FU
TU
RE
I,2004
[8]
n=
27
vs.
15
de
nov
oco
ronary
lesi
ons
ever
olim
us
coate
dS-S
tent
vs.
S-S
tent
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:M
AC
Esi
ngle
centr
e,G
erm
any
QC
Afo
llow
-up
dura
tion:
686
SP
IRIT
I,0
[9,
10,
11]
n=
28
vs.
32
pati
ents
wit
hde
nov
onati
ve
coro
nary
art
ery
lesi
ons
XIE
NC
Evs.
MU
LT
I-L
INK
VIS
ION
mult
ives
sel
trea
tmen
t:no
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:in
-ste
nt
late
loss
, QC
Afo
llow
-up
dura
tion:
1y
cont
inue
d...
2.1. AVAILABLE RCTS 31
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
SP
IRIT
II,
0[]
n=
223
vs.
77
De
nov
ole
sions
(maxim
imtw
o)
XIE
NC
EV
vs.
TA
XU
SE
XP
RE
SS2
single
-blind
(pati
ent)
Para
llel
gro
ups
Pri
mary
endp
oin
t:In
-ste
nt
late
loss
,
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
SC
OR
E,
2004
[12,
13]
n=
126
vs.
140
pati
ents
wit
hfo
cal,
de
nov
oco
ronary
lesi
ons
QuaD
DS
sten
ts(p
acl
itaxel
)vs.
unco
ate
dco
ntr
ol
sten
tsop
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:none
mult
icen
ter,
Worl
dw
ide
QC
Afo
llow
-up
dura
tion:
676
TA
XU
SIV
,2004
[14]
n=
662
vs.
652
Sta
ble
or
unst
able
AP
,pro
voka
ble
isch
aem
iaw
ith
asi
ngle
,pre
vio
usl
yuntr
eate
dco
ronary
-art
ery
sten
osi
s(v
esse
ldia
met
er,
2.5
to3.7
5m
m;
lesi
on
length
,10
to28
mm
)
TA
XU
Svs.
EX
PR
ESS
double
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:T
VR
73
centr
es,
Unit
edSta
tes
QC
Afo
llow
-up
dura
tion:
943
TA
XU
SI,
2003
[15]
n=
31
vs.
30
Sta
ble
or
unst
able
AP
,si
lent
isch
aem
ia;
single
de
nov
oor
rest
enoti
cco
ronary
lesi
ons
TA
XU
SN
IRvs.
NIR
sten
tdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:C
om
bin
ati
on
of
dea
th,A
MI,
TV
R,
sten
tth
rom
bosi
s3
centr
es,
Ger
many
QC
Afo
llow
-up
dura
tion:
697
TA
XU
SII
,2003
[16]
n=
266
vs.
270
Sta
ble
or
unst
able
AP
,si
lent
isch
aem
ia;
single
de
nov
ota
rget
lesi
on
wit
hes
tim
ate
dst
enosi
s>
50%
and
<99%
,
TA
XU
Svs.
NIR
sten
tdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:N
eoin
tim
al
pro
life
ra-
tion
38
centr
es,
Glo
bal
QC
Afo
llow
-up
dura
tion:
697
Paclita
xel,
non-p
oly
meri
celu
ting
stentvers
us
bare
-meta
lst
ent
cont
inue
d...
32 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
DE
LIV
ER
,2004
[17,
18,
19]
n=
524
vs.
519
pati
ents
wit
hfo
cal
de
nov
oco
ronary
lesi
ons,
<25
mm
inle
ngth
,in
2.5
-to
4.0
-mm
ves
sels
non-p
oly
mer
-base
dpacl
itaxel
-coate
dA
CH
IEV
Est
ent
vs.
stain
less
stee
lM
ult
i-L
ink
(ML
)P
EN
TA
sten
t
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:ta
rget
-ves
sel
failure
61
centr
es,
US
QC
Afo
llow
-up
dura
tion:
843
EL
UT
ES,
2004
[20]
n=
152
vs.
38
single
de
nov
oty
pe
Aor
typ
eB
1le
sions
15
mm
length
ina
nati
vec
oro
nary
art
ery
coate
dV
-Fle
xP
lus
vs.
V-F
lex
Plu
sop
enP
ara
llel
gro
ups
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mary
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oin
t:p
erce
nt
dia
met
erst
eno-
sis
mult
icen
ter,
Euro
pe
QC
Afo
llow
-up
dura
tion:
690
ASP
EC
T,
2003
[21]
n=
117
vs.
58
pati
ents
wit
hdis
cret
eco
ronary
lesi
ons
(<15
mm
inle
ngth
,2.2
5to
3.5
mm
india
met
er)
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-Gst
ent
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double
-blind
Para
llel
gro
ups
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mary
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oin
t:st
enosi
sp
erce
nta
ge
mult
icen
ter,
NA
QC
Afo
llow
-up
dura
tion:
689
PA
TE
NC
Y,
2002
[22]
n=
24
vs.
26
Pati
ents
wit
hde
nov
ole
sions
of
2.7
-to
4.0
-mm
dia
met
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ived
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Logic
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Xpacl
itaxel
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nary
Ste
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blind
Para
llel
gro
ups
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mary
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t:N
Am
ult
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ter,
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Afo
llow
-up
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Sirolim
us
elu
ting
stentvers
us
bare
-meta
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Ort
ola
ni
etal,
2007
[23]
n=
NA
vs.
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sym
pto
mati
cco
ronary
art
ery
dis
ease
and
targ
etves
sel
dia
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-blind
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Pri
mary
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t:L
ate
lum
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ss1
centr
es,
cont
inue
d...
2.1. AVAILABLE RCTS 33
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Koch
iadakis
,2007
[24]
n=
38
vs.
43
one-
ves
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isea
se(>
70%
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lum
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and
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eluti
ng
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tsvs.
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mary
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t:in
flam
mato
ryre
sponse
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e
Pach
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al,
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[25]
n=
250
vs.
250
wit
hsy
mpto
mati
cco
ronary
art
ery
dis
ease
and
signifi
cant
angio
gra
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osi
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ups
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mary
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t:B
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Ger
many
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IRIU
S,
2004
[26]
n=
50
vs.
50
Sta
ble
or
unst
able
AP
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lent
isch
aem
iaco
ate
dB
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OC
ITY
vs.
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double
-blind
Para
llel
gro
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mary
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t:M
inim
al
lum
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me-
ter
8ce
ntr
es,
Canada
QC
Afo
llow
-up
dura
tion:
886
SIR
IUS,
2003
[27,
28]
n=
533
vs.
525
Sta
ble
or
unst
able
AP
,si
gns
of
myoca
rdia
lis
chaem
iaSE
Svs.
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tydouble
-blind
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llel
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mary
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om
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53
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edSta
tes
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Afo
llow
-up
dura
tion:
866
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IRIU
S,
2003
[29]
n=
175
vs.
177
Sta
ble
or
unst
able
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,si
lent
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ia;
single
-ves
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or
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but
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new
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wit
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than
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centr
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-up
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cont
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d...
34 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
RA
VE
L,
2002
[30,
31]
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120
vs.
118
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ble
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,si
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-blind
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ate
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-up
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689
Zota
rolim
us
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bare
-meta
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DE
AV
OR
II,
2006
[32,
33,
34,
35]
n=
598
vs.
599
single
de
nov
onati
ve
coro
nary
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ery
sten
osi
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VE
Zota
rolim
us-
Elu
ting
Dri
ver
vs.
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Para
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ups
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mary
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t:ta
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sel
failure
72
centr
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worl
dw
ide
2.2. META-ANALYSIS RESULTS 35
2.2 Meta-analysis results
The results are detailed in table 2.2 (page 37). This table is followed by the Forest’s plotcorresponding to each endpoint.
Dactinomycin eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between dactinomycin eluting stent andbare-metal stent, with a RR of 0.44 (95%CI 0.03 to 6.89, p=0.5549) in favour of dactinomycineluting stent. In other words, all cause death was slightly lower in the dactinomycin elutingstent group , but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 2.61 (95% CI 0.32 to 21.42, p=0.3714).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of dactinomycin eluting stent in MACE, with a RRof 0.07 (95% CI 0.04 to 0.11, p=0.0000).
The single study eligible for this comparison provided data on target lesion revascular-isation . No statistically significant difference between the groups was found in target lesionrevascularisation , with a RR of 0.26 (95% CI 0.06 to 1.07, p=0.0624).
The single study eligible for this comparison provided data on CABG. The analysis detecteda statistically significant difference in favor of dactinomycin eluting stent in CABG, with a RRof 0.09 (95% CI 0.01 to 0.74, p=0.0250).
Everolimus eluting stent versus bare-metal stent
Data from 3 (among 5) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between everolimus eluting stent and bare-metal stent, with a RR of 1.00 (95%CI 0.34 to 2.96, p=0.9929) in favour of everolimus elutingstent. In other words, all cause death was slightly lower in the everolimus eluting stent group, but this was not statistically significant. No heterogeneity across these trials was detected (p=0.9953, I2 = 0.00%).
Data from 2 (among 5) trials evaluating cardiac death were available. When pooled to-gether, there was no statistically significant difference between the groups in cardiac death, witha RR of 0.65 (95% CI 0.17 to 2.40, p=0.5149). No heterogeneity across these trials was detected(p =0.4069, I2 = 0.00%).
Data from 3 (among 5) trials evaluating MI (fatal and non fatal) were available. Whenpooled together, there was no statistically significant difference between the groups in MI (fataland non fatal), with a RR of 0.66 (95% CI 0.34 to 1.26, p=0.2057). No heterogeneity acrossthese trials was detected (p =0.6190, I2 = 0.00%).
Data from 4 (among 5) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of everolimus eluting stent in MACE, with a RR of0.55 (95% CI 0.37 to 0.82, p=0.0031). No heterogeneity across these trials was detected (p=0.8420, I2 = 0.00%).
Data from 4 (among 5) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of everolimus eluting stentin target lesion revascularisation , with a RR of 0.53 (95% CI 0.31 to 0.91, p=0.0210). Noheterogeneity across these trials was detected (p =0.7667, I2 = 0.00%).
Only one of the 5 studies eligible for this comparison provided data on CABG. No statisti-cally significant difference between the groups was found in CABG, with a RR of 0.35 (95% CI0.01 to 17.25, p=0.5941).
Paclitaxel eluting stent versus bare-metal stent
36 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
All the 4 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxeleluting stent and bare-metal stent, with a RR of 1.23 (95%CI 0.50 to 3.02, p=0.6560) in favourof bare-metal stent. In other words, all cause death was slightly lower in the bare-metal stentgroup , but this was not statistically significant. No heterogeneity across these trials was detected(p =0.3792, I2 = 0.03%).
Data from 2 (among 4) trials evaluating cardiac death were available. When pooled to-gether, there was no statistically significant difference between the groups in cardiac death, witha RR of 2.41 (95% CI 0.35 to 16.71, p=0.3745). No heterogeneity across these trials was detected(p =0.1648, I2 = 0.48%).
All the 4 studies had extractable data about the number of participants with MI (fataland non fatal). The analysis detected a statistically significant difference in favor of bare-metal stent in MI (fatal and non fatal), with a RR of 2.77 (95% CI 1.06 to 7.21, p=0.0374). Noheterogeneity across these trials was detected (p =0.6839, I2 = 0.00%).
All the 4 studies had extractable data about the number of participants with MACE. Whenpooled together, there was no statistically significant difference between the groups in MACE,with a RR of 0.66 (95% CI 0.40 to 1.07, p=0.0934). A random effect model was used becausethere was a substantial statistical heterogeneity detected between the studies (p =0.0081, I2 =0.75%).
Data from 2 (among 4) trials evaluating target-vessel revascularization were available.When pooled together, there was no statistically significant difference between the groups intarget-vessel revascularization, with a RR of 0.57 (95% CI 0.27 to 1.21, p=0.1422). A randomeffect model was used because there was a substantial statistical heterogeneity detected betweenthe studies (p =0.0144, I2 = 0.83%).
Data from 3 (among 4) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of paclitaxel eluting stentin target lesion revascularisation , with a RR of 0.27 (95% CI 0.19 to 0.40, p=0.0000). Noheterogeneity across these trials was detected (p =0.9151, I2 = 0.00%).
Only one of the 4 studies eligible for this comparison provided data on in-lesion binaryrestenosis . The analysis detected a statistically significant difference in favor of paclitaxeleluting stent in in-lesion binary restenosis , with a RR of 0.30 (95% CI 0.19 to 0.47, p=0.0000).
Only one of the 4 studies eligible for this comparison provided data on angiographicrestenosis . The analysis detected a statistically significant difference in favor of paclitaxeleluting stent in angiographic restenosis , with a RR of 0.23 (95% CI 0.18 to 0.30, p=0.0000).
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
All the 4 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxel,non-polymeric eluting stent and bare-metal stent, with a RR of 0.42 (95%CI 0.10 to 1.81,p=0.2461) in favour of paclitaxel, non-polymeric eluting stent. In other words, all cause deathwas slightly lower in the paclitaxel, non-polymeric eluting stent group , but this was not statis-tically significant. No heterogeneity across these trials was detected (p =0.9168, I2 = 0.00%).
All the 4 studies had extractable data about the number of participants with MI (fatal andnon fatal). When pooled together, there was no statistically significant difference between thegroups in MI (fatal and non fatal), with a RR of 0.97 (95% CI 0.19 to 4.99, p=0.9689). Noheterogeneity across these trials was detected (p =0.8212, I2 = 0.00%).
All the 4 studies had extractable data about the number of participants with MACE. Whenpooled together, there was no statistically significant difference between the groups in MACE,with a RR of 0.74 (95% CI 0.52 to 1.05, p=0.0958). No heterogeneity across these trials wasdetected (p =0.4882, I2 = 0.00%).
All the 4 studies had extractable data about the number of participants with target lesion
2.2. META-ANALYSIS RESULTS 37
revascularisation . When pooled together, there was no statistically significant differencebetween the groups in target lesion revascularisation , with a RR of 0.42 (95% CI 0.10 to 1.81,p=0.2461). No heterogeneity across these trials was detected (p =0.9168, I2 = 0.00%).
Sirolimus eluting stent versus bare-metal stent
Data from 5 (among 7) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 1.42 (95%CI 0.67 to 3.01, p=0.3585) in favour of bare-metal stent.In other words, all cause death was slightly lower in the bare-metal stent group , but this wasnot statistically significant. No heterogeneity across these trials was detected (p =0.9903, I2 =0.00%).
Data from 4 (among 7) trials evaluating MI (fatal and non fatal) were available. Whenpooled together, there was no statistically significant difference between the groups in MI (fataland non fatal), with a RR of 0.98 (95% CI 0.58 to 1.66, p=0.9480). No heterogeneity acrossthese trials was detected (p =0.5757, I2 = 0.00%).
Data from 5 (among 7) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of 0.38(95% CI 0.26 to 0.55, p=0.0000). No heterogeneity across these trials was detected (p =0.0741,I2 = 0.53%).
Only one of the 7 studies eligible for this comparison provided data on target-vessel revas-cularization. The analysis detected a statistically significant difference in favor of sirolimuseluting stent in target-vessel revascularization, with a RR of 0.41 (95% CI 0.30 to 0.57, p=0.0000).
Data from 5 (among 7) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of sirolimus eluting stentin target lesion revascularisation , with a RR of 0.25 (95% CI 0.16 to 0.39, p=0.0000). Noheterogeneity across these trials was detected (p =0.1772, I2 = 0.37%).
Data from 4 (among 7) trials evaluating CABG were available. When pooled together,there was no statistically significant difference between the groups in CABG, with a RR of 0.46(95% CI 0.16 to 1.30, p=0.1426). No heterogeneity across these trials was detected (p =0.6684,I2 = 0.00%).
Zotarolimus eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of zotarolimus eluting stent in MACE, with a RR of0.50 (95% CI 0.36 to 0.71, p=0.0000).
The single study eligible for this comparison provided data on angiographic restenosis .The analysis detected a statistically significant difference in favor of zotarolimus eluting stent inangiographic restenosis , with a RR of 0.39 (95% CI 0.28 to 0.55, p=0.0000).
Table 2.2: Results details - Unparticular patients - comparison versus bare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Dactinomycin eluting stent versus bare-metal stent
All cause death RR=0.44 [0.03;6.89] 0.5549 1.0000 (I=0.00) 1 343
MI (fatal and non fatal) RR=2.61 [0.32;21.42] 0.3714 1.0000 (I=0.00) 1 343
MACE RR=0.07 [0.04;0.11] 0.0000 1.0000 (I=0.00) 1 343
target lesion revascularisation RR=0.26 [0.06;1.07] 0.0624 1.0000 (I=0.00) 1 343
CABG RR=0.09 [0.01;0.74] 0.0250 1.0000 (I=0.00) 1 343
Everolimus eluting stent versus bare-metal stent
continued...
38 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Comparison Endpoint Effect 95% CI p ass hom k n
All cause death RR=1.00 [0.34;2.96] 0.9929 0.9953 (I=0.00) 3 1078
cardiac death RR=0.65 [0.17;2.40] 0.5149 0.4069 (I=0.00) 2 1276
MI (fatal and non fatal) RR=0.66 [0.34;1.26] 0.2057 0.6190 (I=0.00) 3 1333
MACE RR=0.55 [0.37;0.82] 0.0031 0.8420 (I=0.00) 4 1373
target lesion revascularisation RR=0.53 [0.31;0.91] 0.0210 0.7667 (I=0.00) 4 1378
CABG RR=0.35 [0.01;17.25] 0.5941 1.0000 (I=0.00) 1 300
Stent thrombosis (any, end offollow up)
RR=1.21 [0.27;5.47] 0.8023 0.9743 (I=0.00) 2 1024
4y stent thrombosis (ARC) RR=1.35 [0.43;4.19] 0.6088 1.0000 (I=0.00) 1 971
Acute stent thrombosis(<=24h)
RR=0.35 [0.01;17.25] 0.5941 1.0000 (I=0.00) 1 300
sub acute stent thrombosis(1-30 days)
RR=0.35 [0.01;17.25] 0.5941 1.0000 (I=0.00) 1 300
late stent thrombosis (31days -1year)
RR=0.35 [0.02;5.45] 0.4501 1.0000 (I=0.00) 1 300
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=1.23 [0.50;3.02] 0.6560 0.3792 (I=0.03) 4 2137
cardiac death RR=2.41 [0.35;16.71] 0.3745 0.1648 (I=0.48) 2 1580
MI (fatal and non fatal) RR=2.77 [1.06;7.21] 0.0374 0.6839 (I=0.00) 4 2137
MACE RR=0.66 [0.40;1.07] 0.0934 0.0081 (I=0.75) 4 2164
target-vessel revascularization RR=0.57 [0.27;1.21] 0.1422 0.0144 (I=0.83) 2 1580
target lesion revascularisation RR=0.27 [0.19;0.40] 0.0000 0.9151 (I=0.00) 3 1898
in-lesion binary restenosis RR=0.30 [0.19;0.47] 0.0000 1.0000 (I=0.00) 1 1314
Stent thrombosis (any, end offollow up)
RR=3.27 [0.55;19.33] 0.1920 0.0666 (I=0.58) 4 2137
sub acute stent thrombosis(1-30 days)
RR=0.98 [0.14;6.91] 0.9838 1.0000 (I=0.00) 1 1314
late stent thrombosis (31days -1year)
RR=2.02 [0.76;5.37] 0.1563 0.8457 (I=0.00) 3 1911
angiographic restenosis RR=0.23 [0.18;0.30] 0.0000 1.0000 (I=0.00) 1 559
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
All cause death RR=0.42 [0.10;1.81] 0.2461 0.9168 (I=0.00) 4 1446
MI (fatal and non fatal) RR=0.97 [0.19;4.99] 0.9689 0.8212 (I=0.00) 4 1446
MACE RR=0.74 [0.52;1.05] 0.0958 0.4882 (I=0.00) 4 1444
target lesion revascularisation RR=0.42 [0.10;1.81] 0.2461 0.9168 (I=0.00) 4 1446
Stent thrombosis (any, end offollow up)
RR=0.97 [0.26;3.61] 0.9620 0.6062 (I=0.00) 4 1446
late stent thrombosis (31days -1year)
RR=0.57 [0.08;4.00] 0.5684 0.8414 (I=0.00) 3 1398
Sirolimus eluting stent versus bare-metal stent
All cause death RR=1.42 [0.67;3.01] 0.3585 0.9903 (I=0.00) 5 2248
MI (fatal and non fatal) RR=0.98 [0.58;1.66] 0.9480 0.5757 (I=0.00) 4 1748
MACE RR=0.38 [0.26;0.55] 0.0000 0.0741 (I=0.53) 5 2248
target-vessel revascularization RR=0.41 [0.30;0.57] 0.0000 1.0000 (I=0.00) 1 1058
target lesion revascularisation RR=0.25 [0.16;0.39] 0.0000 0.1772 (I=0.37) 5 2248
CABG RR=0.46 [0.16;1.30] 0.1426 0.6684 (I=0.00) 4 1748
Stent thrombosis (any, end offollow up)
RR=0.86 [0.25;2.95] 0.8044 0.7065 (I=0.00) 4 1748
late stent thrombosis (31days -1year)
RR=0.51 [0.11;2.41] 0.3950 0.9460 (I=0.00) 4 1748
continued...
2.2. META-ANALYSIS RESULTS 39
Comparison Endpoint Effect 95% CI p ass hom k n
Zotarolimus eluting stent versus bare-metal stent
MACE RR=0.50 [0.36;0.71] 0.0000 1.0000 (I=0.00) 1 1197
Stent thrombosis (any, end offollow up)
RR=0.43 [0.11;1.65] 0.2188 1.0000 (I=0.00) 1 1197
angiographic restenosis RR=0.39 [0.28;0.55] 0.0000 1.0000 (I=0.00) 1 600
40 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 2.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Dactinomycin eluting stent versus bare-metal stent
ACTION,2004 1/239 1/104 0.44 [0.03;6.89]
Global p ass= 0.5549 0.44 [0.03;6.89]
Everolimus eluting stent versus bare-metal stent
SPIRIT III,2008 8/655 4/321 0.98 [0.30;3.23]
FUTURE I,2004 1/27 0/15 1.11 [0.04;31.22]
SPIRIT I 0/28 0/32 1.14 [0.02;55.73]
Global p ass= 0.9929 1.00 [0.34;2.96]
Het. between 3 trials p=0.9953 I2=0.00
Paclitaxel eluting stent versus bare-metal stent
SCORE,2004 5/126 0/140 11.11 [0.61;201.36]
TAXUS IV,2004 9/662 8/652 1.11 [0.43;2.85]
TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]
TAXUS II,2003 0/226 2/270 0.30 [0.01;6.59]
Global p ass= 0.6560 1.23 [0.50;3.02]
Het. between 4 trials p=0.3792 I2=0.03
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
DELIVER,2004 1/517 4/512 0.25 [0.03;2.21]
ELUTES,2004 1/152 0/38 0.50 [0.02;14.63]
ASPECT,2003 1/118 0/59 1.00 [0.03;29.38]
PATENCY,2002 0/24 1/26 0.54 [0.02;15.43]
Global p ass= 0.2461 0.42 [0.10;1.81]
Het. between 4 trials p=0.9168 I2=0.00
Sirolimus eluting stent versus bare-metal stent
Pache et al,2005 7/250 5/250 1.40 [0.45;4.35]
C-SIRIUS,2004 0/50 0/50 1.00 [0.02;49.42]
SIRIUS,2003 5/533 3/525 1.64 [0.39;6.83]
E-SIRIUS,2003 2/175 1/177 2.02 [0.19;22.11]
RAVEL,2002 2/120 2/118 0.98 [0.14;6.87]
Global p ass= 0.3585 1.42 [0.67;3.01]
Het. between 5 trials p=0.9903 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
2.2. META-ANALYSIS RESULTS 41
Figure 2.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Everolimus eluting stent versus bare-metal stent
SPIRIT III,2008 5/655 3/321 0.82 [0.20;3.40]
SPIRIT II 0/223 1/77 0.17 [0.01;5.10]
Global p ass= 0.5149 0.65 [0.17;2.40]
Het. between 2 trials p=0.4069 I2=0.00
Paclitaxel eluting stent versus bare-metal stent
SCORE,2004 5/126 0/140 11.11 [0.61;201.36]
TAXUS IV,2004 /662 /652 1.27 [0.47;3.40]
Global p ass= 0.3745 2.41 [0.35;16.71]
Het. between 2 trials p=0.1648 I2=0.48
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
42 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 2.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Dactinomycin eluting stent versus bare-metal stent
ACTION,2004 6/239 1/104 2.61 [0.32;21.42]
Global p ass= 0.3714 2.61 [0.32;21.42]
Everolimus eluting stent versus bare-metal stent
SPIRIT III,2008 18/653 13/320 0.68 [0.34;1.37]
SPIRIT I 1/28 0/32 2.29 [0.08;65.59]
SPIRIT II 2/223 2/77 0.35 [0.05;2.41]
Global p ass= 0.2057 0.66 [0.34;1.26]
Het. between 3 trials p=0.6190 I2=0.00
Paclitaxel eluting stent versus bare-metal stent
SCORE,2004 6/126 0/140 13.33 [0.75;236.34]
TAXUS IV,2004 5/662 2/652 2.46 [0.48;12.65]
TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]
TAXUS II,2003 6/226 3/270 2.39 [0.60;9.45]
Global p ass= 0.0374 2.77 [1.06;7.21]
Het. between 4 trials p=0.6839 I2=0.00
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
DELIVER,2004 2/517 1/512 1.98 [0.18;21.78]
ELUTES,2004 0/152 0/38 0.25 [0.01;12.40]
ASPECT,2003 0/118 0/59 0.50 [0.01;24.89]
PATENCY,2002 0/24 0/26 1.08 [0.02;52.49]
Global p ass= 0.9689 0.97 [0.19;4.99]
Het. between 4 trials p=0.8212 I2=0.00
Sirolimus eluting stent versus bare-metal stent
C-SIRIUS,2004 1/50 2/50 0.50 [0.05;5.34]
SIRIUS,2003 15/533 17/525 0.87 [0.44;1.72]
E-SIRIUS,2003 8/175 4/177 2.02 [0.62;6.60]
RAVEL,2002 4/120 5/118 0.79 [0.22;2.86]
Global p ass= 0.9480 0.98 [0.58;1.66]
Het. between 4 trials p=0.5757 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
2.2. META-ANALYSIS RESULTS 43
Figure 2.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Dactinomycin eluting stent versus bare-metal stent
ACTION,2004 14/239 90/104 0.07 [0.04;0.11]
Global p ass= 0.0000 0.07 [0.04;0.11]
Everolimus eluting stent versus bare-metal stent
SPIRIT III,2008 39/653 33/320 0.58 [0.37;0.90]
FUTURE I,2004 2/26 1/14 1.08 [0.11;10.86]
SPIRIT I 2/28 6/32 0.38 [0.08;1.74]
SPIRIT II 6/223 5/77 0.41 [0.13;1.32]
Global p ass= 0.0031 0.55 [0.37;0.82]
Het. between 4 trials p=0.8420 I2=0.00
Paclitaxel eluting stent versus bare-metal stent
SCORE,2004 37/126 35/140 1.17 [0.79;1.74]
TAXUS IV,2004 56/662 98/652 0.56 [0.41;0.77]
TAXUS I,2003 1/31 3/30 0.32 [0.04;2.93]
TAXUS II,2003 27/260 57/263 0.48 [0.31;0.73]
Global (random effect) p ass= 0.0934 0.66 [0.40;1.07]
fixed effect model p ass= 0.0000 0.66 [0.54;0.82]
Het. between 4 trials p=0.0081 I2=0.75
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
DELIVER,2004 34/517 44/512 0.77 [0.50;1.18]
ELUTES,2004 15/152 7/38 0.54 [0.24;1.22]
ASPECT,2003 10/117 3/58 1.65 [0.47;5.77]
PATENCY,2002 3/24 6/26 0.54 [0.15;1.93]
Global p ass= 0.0958 0.74 [0.52;1.05]
Het. between 4 trials p=0.4882 I2=0.00
Sirolimus eluting stent versus bare-metal stent
Pache et al,2005 34/250 56/250 0.61 [0.41;0.90]
C-SIRIUS,2004 2/50 9/50 0.22 [0.05;0.98]
SIRIUS,2003 38/533 99/525 0.38 [0.27;0.54]
E-SIRIUS,2003 14/175 40/177 0.35 [0.20;0.63]
RAVEL,2002 7/120 35/118 0.20 [0.09;0.43]
Global p ass= 0.0000 0.38 [0.26;0.55]
Het. between 5 trials p=0.0741 I2=0.53
Zotarolimus eluting stent versus bare-metal stent
ENDEAVOR II,2006 44/598 88/599 0.50 [0.36;0.71]
Global p ass= 0.0000 0.50 [0.36;0.71]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
44 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 2.5: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
SCORE,2004 25/126 33/140 0.84 [0.53;1.33]
TAXUS IV,2004 /662 /652 0.39 [0.26;0.59]
Global (random effect) p ass= 0.1422 0.57 [0.27;1.21]
fixed effect model p ass= 0.0000 0.55 [0.40;0.74]
Het. between 2 trials p=0.0144 I2=0.83
Sirolimus eluting stent versus bare-metal stent
SIRIUS,2003 46/533 110/525 0.41 [0.30;0.57]
Global p ass= 0.0000 0.41 [0.30;0.57]
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
2.2. META-ANALYSIS RESULTS 45
Figure 2.6: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Dactinomycin eluting stent versus bare-metal stent
ACTION,2004 3/239 5/104 0.26 [0.06;1.07]
Global p ass= 0.0624 0.26 [0.06;1.07]
Everolimus eluting stent versus bare-metal stent
SPIRIT III,2008 22/655 18/321 0.60 [0.33;1.10]
FUTURE I,2004 1/27 1/15 0.56 [0.04;8.26]
SPIRIT I 1/28 6/32 0.19 [0.02;1.49]
SPIRIT II 4/223 3/77 0.46 [0.11;2.01]
Global p ass= 0.0210 0.53 [0.31;0.91]
Het. between 4 trials p=0.7667 I2=0.00
Paclitaxel eluting stent versus bare-metal stent
TAXUS IV,2004 20/662 74/652 0.27 [0.16;0.43]
TAXUS I,2003 0/31 3/30 0.16 [0.01;3.09]
TAXUS II,2003 11/260 38/263 0.29 [0.15;0.56]
Global p ass= 0.0000 0.27 [0.19;0.40]
Het. between 3 trials p=0.9151 I2=0.00
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
DELIVER,2004 1/517 4/512 0.25 [0.03;2.21]
ELUTES,2004 1/152 0/38 0.50 [0.02;14.63]
ASPECT,2003 1/118 0/59 1.00 [0.03;29.38]
PATENCY,2002 0/24 1/26 0.54 [0.02;15.43]
Global p ass= 0.2461 0.42 [0.10;1.81]
Het. between 4 trials p=0.9168 I2=0.00
Sirolimus eluting stent versus bare-metal stent
Pache et al,2005 18/250 47/250 0.38 [0.23;0.64]
C-SIRIUS,2004 2/50 9/50 0.22 [0.05;0.98]
SIRIUS,2003 22/533 87/525 0.25 [0.16;0.39]
E-SIRIUS,2003 7/175 37/177 0.19 [0.09;0.42]
RAVEL,2002 0/120 27/118 0.02 [0.00;0.30]
Global p ass= 0.0000 0.25 [0.16;0.39]
Het. between 5 trials p=0.1772 I2=0.37
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
46 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 2.7: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Dactinomycin eluting stent versus bare-metal stent
ACTION,2004 1/239 5/104 0.09 [0.01;0.74]
Global p ass= 0.0250 0.09 [0.01;0.74]
Everolimus eluting stent versus bare-metal stent
SPIRIT II 0/223 0/77 0.35 [0.01;17.25]
Global p ass= 0.5941 0.35 [0.01;17.25]
Sirolimus eluting stent versus bare-metal stent
C-SIRIUS,2004 1/50 0/50 2.00 [0.07;58.28]
SIRIUS,2003 3/533 8/525 0.37 [0.10;1.38]
E-SIRIUS,2003 0/175 3/177 0.17 [0.01;3.34]
RAVEL,2002 1/120 1/118 0.98 [0.06;15.54]
Global p ass= 0.1426 0.46 [0.16;1.30]
Het. between 4 trials p=0.6684 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 2.8: Forest’s plot for in-lesion binary restenosis
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS IV,2004 /662 /652 0.30 [0.19;0.47]
Global p ass= 0.0000 0.30 [0.19;0.47]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
2.2. META-ANALYSIS RESULTS 47
Figure 2.9: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Everolimus eluting stent versus bare-metal stent
SPIRIT III,2008 5/647 2/317 1.22 [0.24;6.28]
SPIRIT I 0/28 0/32 1.14 [0.02;55.73]
Global p ass= 0.8023 1.21 [0.27;5.47]
Het. between 2 trials p=0.9743 I2=0.00
Paclitaxel eluting stent versus bare-metal stent
SCORE,2004 13/126 1/140 14.44 [1.92;108.85]
TAXUS IV,2004 4/662 5/652 0.79 [0.21;2.92]
TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]
TAXUS II,2003 5/226 0/270 11.95 [0.66;217.51]
Global p ass= 0.1920 3.27 [0.55;19.33]
Het. between 4 trials p=0.0666 I2=0.58
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
DELIVER,2004 2/517 2/512 0.99 [0.14;7.00]
ELUTES,2004 1/152 1/38 0.25 [0.02;3.91]
ASPECT,2003 4/118 0/59 4.00 [0.22;74.41]
PATENCY,2002 0/24 0/26 1.08 [0.02;52.49]
Global p ass= 0.9620 0.97 [0.26;3.61]
Het. between 4 trials p=0.6062 I2=0.00
Sirolimus eluting stent versus bare-metal stent
C-SIRIUS,2004 1/50 1/50 1.00 [0.06;15.55]
SIRIUS,2003 2/533 4/525 0.49 [0.09;2.68]
E-SIRIUS,2003 2/175 0/177 4.05 [0.18;89.09]
RAVEL,2002 0/120 0/118 0.98 [0.02;49.15]
Global p ass= 0.8044 0.86 [0.25;2.95]
Het. between 4 trials p=0.7065 I2=0.00
Zotarolimus eluting stent versus bare-metal stent
ENDEAVOR II,2006 3/598 7/599 0.43 [0.11;1.65]
Global p ass= 0.2188 0.43 [0.11;1.65]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
48 CHAPTER 2. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 2.10: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Everolimus eluting stent versus bare-metal stent
SPIRIT III,2008 11/652 4/319 1.35 [0.43;4.19]
Global p ass= 0.6088 1.35 [0.43;4.19]
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 2.11: Forest’s plot for acute stent thrombosis (<=24h)
Trial studied T. control T. RR [95%CI]
Everolimus eluting stent versus bare-metal stent
SPIRIT II 0/223 0/77 0.35 [0.01;17.25]
Global p ass= 0.5941 0.35 [0.01;17.25]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 2.12: Forest’s plot for sub acute stent thrombosis (1-30 days)
Trial studied T. control T. RR [95%CI]
Everolimus eluting stent versus bare-metal stent
SPIRIT II 0/223 0/77 0.35 [0.01;17.25]
Global p ass= 0.5941 0.35 [0.01;17.25]
Paclitaxel eluting stent versus bare-metal stent
TAXUS IV,2004 /662 /652 0.98 [0.14;6.91]
Global p ass= 0.9838 0.98 [0.14;6.91]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
2.2. META-ANALYSIS RESULTS 49
Figure 2.13: Forest’s plot for late stent thrombosis (31days - 1year)
Trial studied T. control T. RR [95%CI]
Everolimus eluting stent versus bare-metal stent
SPIRIT II 1/223 1/77 0.35 [0.02;5.45]
Global p ass= 0.4501 0.35 [0.02;5.45]
Paclitaxel eluting stent versus bare-metal stent
TAXUS IV,2004 /662 /652 1.97 [0.68;5.72]
TAXUS I,2003 0/31 0/30 0.97 [0.02;47.23]
TAXUS II,2003 2/266 0/270 4.06 [0.18;89.62]
Global p ass= 0.1563 2.02 [0.76;5.37]
Het. between 3 trials p=0.8457 I2=0.00
Paclitaxel, non-polymeric eluting stent versus bare-metal stent
DELIVER,2004 1/522 1/519 0.99 [0.06;15.85]
ELUTES,2004 0/153 0/39 0.25 [0.01;12.65]
ASPECT,2003 0/117 0/48 0.41 [0.01;20.38]
Global p ass= 0.5684 0.57 [0.08;4.00]
Het. between 3 trials p=0.8414 I2=0.00
Sirolimus eluting stent versus bare-metal stent
C-SIRIUS,2004 0/50 1/50 0.50 [0.02;14.57]
SIRIUS,2003 1/533 3/525 0.33 [0.03;3.15]
E-SIRIUS,2003 0/175 0/177 1.01 [0.02;50.69]
RAVEL,2002 0/120 0/118 0.98 [0.02;49.15]
Global p ass= 0.3950 0.51 [0.11;2.41]
Het. between 4 trials p=0.9460 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
50 REFERENCES
Figure 2.14: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS IV,2004 /292 /267 0.23 [0.18;0.30]
Global p ass= 0.0000 0.23 [0.18;0.30]
Zotarolimus eluting stent versus bare-metal stent
ENDEAVOR II,2006 40/298 103/302 0.39 [0.28;0.55]
Global p ass= 0.0000 0.39 [0.28;0.55]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
References
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[26] Schampaert E, Cohen EA, Schlter M, Reeves F, Traboulsi M, Title LM, Kuntz RE, Popma JJ. The Canadianstudy of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small nativecoronary arteries (C-SIRIUS).. J Am Coll Cardiol 2004;43:1110-5 [PMID=15028375]
[27] Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ,Williams DO, Teirstein PS, Jaeger JL, Kuntz RE. Sirolimus-eluting stents versus standard stents in patientswith stenosis in a native coronary artery.. N Engl J Med 2003;349:1315-23 [PMID=14523139]
[28] Weisz G, Moses JW, Teirstein PS, Holmes DR Jr, Raizner AE, Satler LF, Mishkel G, Wilensky RL,Wang P, Kuntz RE, Popma JJ, Leon MB. Safety of sirolimus-eluting stenting and its effect on resteno-sis in patients with unstable angina pectoris (a SIRIUS substudy).. Am J Cardiol 2007 Apr 15;99:1044-50[PMID=17437725]
[29] Schofer J, Schlter M, Gershlick AH, Wijns W, Garcia E, Schampaert E, Breithardt G. Sirolimus-elutingstents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind,randomised controlled trial (E-SIRIUS).. Lancet 2003;362:1093-9 [PMID=14550694]
[30] Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, BarraganP, Guagliumi G, Molnr F, Falotico R. A randomized comparison of a sirolimus-eluting stent with a standardstent for coronary revascularization.. N Engl J Med 2002;346:1773-80 [PMID=12050336]
[31] Morice MC, Serruys PW, Barragan P, Bode C, Van Es GA, Stoll HP, Snead D, Mauri L, Cutlip DE, SousaE. Long-term clinical outcomes with sirolimus-eluting coronary stents: five-year results of the RAVEL trial..J Am Coll Cardiol 2007 Oct 2;50:1299-304 [PMID=17903626]
[32] Gruberg L.. ENDEAVOR II. A randomized comparison of the Endeavor ABT-578 drug-eluting stent witha bare metal stent for coronary revascularization,powerpo. http://www.medscape.com/viewarticle/501475
[33] Fajadet J, Wijns W, Laarman GJ, Kuck KH, Ormiston J, Mnzel T, Popma JJ, Fitzgerald PJ, Bo-nan R, Kuntz RE. Randomized, double-blind, multicenter study of the Endeavor zotarolimus-elutingphosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angio-graphic results of the ENDEAVOR II trial.. Circulation 2006 Aug 22;114:798-806 [PMID=16908773]
[34] Fajadet J, Wijns W, Laarman GJ, Kuck KH, Ormiston J, Mnzel T, Popma JJ, Fitzgerald PJ, Bo-nan R, Kuntz RE. Randomized, double-blind, multicenter study of the Endeavor zotarolimus-elutingphosphorylcholine-encapsulated stent for treatment of native coronary artery lesions. Clinical and angio-graphic results of the ENDEAVOR II Trial.. Minerva Cardioangiol 2007 Feb;55:1-18 [PMID=17287679]
[35] Sakurai R, Hongo Y, Yamasaki M, Honda Y, Bonneau HN, Yock PG, Cutlip D, Popma JJ, Zimetbaum P,Fajadet J, Kuntz RE, Wijns W, Fitzgerald PJ. Detailed intravascular ultrasound analysis of Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy stent in de novo coronary lesions (results from theENDEAVOR II trial).. Am J Cardiol 2007 Sep 1;100:818-23 [PMID=17719326]
53
3 Detailed results for comparison versus paclitaxel
eluting stent in unparticular patients
3.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent
A total of 10 RCTs which randomized 8233 patients were identified: 1 trial compared CoStarstent with paclitaxel eluting stent , 2 trials compared rapamycin eluting stent with paclitaxeleluting stent and 7 trials compared sirolimus eluting stent with paclitaxel eluting stent (see 3.1page 54).
The average study size was 914 patients per arm (range 100 to 1065 per arm). The firststudy was published in 2005, and the last study was published in 2008.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
All cause death data was reported in 9 trials; 8 trials reported data on MI (fatal and nonfatal); 7 trials reported data on target lesion revascularisation ; 5 trials reported data on MACE;4 trials reported data on target-vessel revascularization; 3 trials reported data on cardiac death;1 trials reported data on in-lesion binary restenosis ; 1 trials reported data on CABG; 1 trialsreported data on angiographic restenosis ; 9 trials reported data on Stent thrombosis (any, endof follow up); 7 trials reported data on 4y stent thrombosis (ARC); 2 trials reported data on latestent thrombosis (31days - 1year); 1 trials reported data on sub acute stent thrombosis (1-30days); and 1 trials reported data on Acute stent thrombosis (¡=24h).
Following table 3.1 (page 54) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus paclitaxel eluting stent.
54CHAPTER 3. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Table
3.1
:M
ain
study
char
act
eris
tics
-U
npar
ticu
lar
pat
ients
-co
mpar
ison
vers
us
pacl
itaxel
eluti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
CoSta
rst
entvers
us
paclita
xelelu
ting
stent
Cost
ar
II,
2008
[1]
n=
989
vs.
686
pati
ent
under
goin
gp
ercu
taneo
us
coro
nary
inte
rven
tion
for
asi
ngle
lesi
on
per
ves
sel
inup
toth
ree
nati
ve
epic
ard
ial
ves
sels
CoSta
rst
ent
(Conor
Med
Syst
ems)
vs.
Taxus
(Bost
on
Sci
enti
fic)
mult
ives
sel
trea
tmen
t:21
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:M
AC
E71
centr
es,
US,
Ger
many,
Bel
giu
m,
and
New
Zea
land
Rapam
ycin
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Wes
sely
,2008
[2]
n=
NA
vs.
NA
rapam
yci
np
oly
mer
-coate
ddru
g-e
luti
ng
sten
tvs.
pacl
itaxel
poly
mer
-coate
ddru
g-e
luti
ng
sten
t
NA
Para
llel
gro
ups
Pri
mary
endp
oin
t:none
1ce
ntr
es,
Ger
many
ISA
R-T
EST
-1,
2006
[3]
n=
225
vs.
225
stable
or
unst
able
angin
aor
ap
osi
tive
stre
sste
st,
stable
or
unst
able
angin
aor
ap
osi
tive
stre
sste
st
rapam
yci
n-e
luti
ng
sten
tY
ukon
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:in
-ste
nt
late
lum
enlo
ss2
centr
es,
Ger
many
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
SO
RT
OU
TII
,2008
[4,
5]
n=
1065
vs.
1033
Unse
lect
edpati
ents
(incl
uded
ST
-seg
men
tel
evati
on
myoca
rdia
lin
farc
tion
(ST
EM
I),
non-S
TE
MI
or
unst
able
angin
ap
ecto
ris,
and
stable
angin
a)
Cypher
sten
tvs.
Taxus
sten
t(B
ost
on
Sci
enti
fic
Corp
)op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:m
ajo
radver
seca
rdia
cev
ents
5ce
ntr
es,
Den
mark
.
Han,
2006
[6]
n=
210
vs.
206
Mult
ives
sel
dis
ease
.Sta
ble
or
unst
able
AP
,no
AM
IC
ypher
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:none
NA
,C
hin
a
Zhang
(SE
Svs
PE
S),
2006
[7]
n=
246
vs.
203
Unse
lect
edpati
ents
.Sta
ble
or
unst
able
AP
,A
CS
wit
hde
nov
oco
ronary
lesi
ons
Cypher
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:dea
th,A
MI,
TV
Rat
30day
s1
centr
es,
Chin
a
cont
inue
d...
3.1. AVAILABLE RCTS 55
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
RE
AL
ITY
,2006
[8]
n=
701
vs.
685
Rel
ati
vel
yunse
lect
edpati
ents
.Sta
ble
or
unst
able
docu
men
ted
sile
nt
isch
aem
ia,
no
AM
Iw
ith
1or
2de
nov
ole
sions
(2.2
5-3
.00
mm
india
met
er)
innati
ve
coro
nary
art
erie
s
Cypher
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s90
centr
es,
Euro
pe,
Lati
nA
mer
ica,
and
Asi
am
QC
Afo
llow
-up
dura
tion:
8m
onth
s
SIR
TA
X(W
indec
ker
),2005
[9]
n=
503
vs.
509
Unse
lect
edpati
ents
.Sta
ble
AP
,A
CS,
incl
udin
gA
MI.
at
least
one
lesi
on
wit
hst
enosi
sof
at
least
50
per
cent
ina
ves
sel
wit
ha
refe
rence
dia
met
erb
etw
een
2.2
5and
4.0
0m
mth
at
was
suit
able
for
sten
tim
pla
nta
tion
Cypher
vs.
Taxus
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:ca
rdia
cdea
th,
AM
I,T
LR
2ce
ntr
es,
Sw
itze
rland
TA
Xi,
2005
[10,
11]
n=
102
vs.
100
Unse
lect
edpati
ents
Cypher
vs.
Taxus
mult
ives
sel
trea
tmen
t:22.0
4op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:C
om
bin
ati
on
of
dea
th,A
MI,
TL
R,
sten
tth
rom
bosi
s1
centr
es,
Sw
itze
rland.
BA
SK
ET
(vs
pacl
itaxel
),2005
[12]
n=
264
vs.
281
Unse
lect
edpati
ents
;de-
nov
ole
sions
Cypher
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:co
st-e
ffec
tiven
ess
1ce
ntr
es,
Sw
itze
rland,
56CHAPTER 3. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
3.2 Meta-analysis results
The results are detailed in table 3.2 (page 57). This table is followed by the Forest’s plotcorresponding to each endpoint.
CoStar stent versus paclitaxel eluting stent
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between coStar stent and paclitaxeleluting stent, with a RR of 0.69 (95%CI 0.20 to 2.39, p=0.5618) in favour of coStar stent. Inother words, all cause death was slightly lower in the coStar stent group , but this was notstatistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 1.47 (95% CI 0.82 to 2.65, p=0.1946).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of paclitaxel eluting stent in MACE, with a RR of1.61 (95% CI 1.16 to 2.23, p=0.0045).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of paclitaxel elutingstent in target-vessel revascularization, with a RR of 1.91 (95% CI 1.27 to 2.89, p=0.0021).
Rapamycin eluting stent versus paclitaxel eluting stent
Only one of the 2 studies eligible for this comparison provided data on all cause death.There was no statistically significant difference in all cause death between rapamycin elutingstent and paclitaxel eluting stent, with a RR of 0.67 (95%CI 0.11 to 3.95, p=0.6552) in favourof rapamycin eluting stent. In other words, all cause death was slightly lower in the rapamycineluting stent group , but this was not statistically significant.
Sirolimus eluting stent versus paclitaxel eluting stent
All the 7 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between sirolimuseluting stent and paclitaxel eluting stent, with a RR of 0.98 (95%CI 0.64 to 1.50, p=0.9272)in favour of sirolimus eluting stent. In other words, all cause death was slightly lower in thesirolimus eluting stent group , but this was not statistically significant. No heterogeneity acrossthese trials was detected (p =0.6672, I2 = 0.00%).
Data from 3 (among 7) trials evaluating cardiac death were available. When pooled to-gether, there was no statistically significant difference between the groups in cardiac death, witha RR of 0.85 (95% CI 0.34 to 2.12, p=0.7231). No heterogeneity across these trials was detected(p =0.2939, I2 = 0.18%).
All the 7 studies had extractable data about the number of participants with MI (fatal andnon fatal). When pooled together, there was no statistically significant difference between thegroups in MI (fatal and non fatal), with a RR of 0.79 (95% CI 0.59 to 1.07, p=0.1298). Noheterogeneity across these trials was detected (p =0.9989, I2 = 0.00%).
Data from 4 (among 7) trials evaluating MACE were available. When pooled together,there was no statistically significant difference between the groups in MACE, with a RR of 0.77(95% CI 0.59 to 1.01, p=0.0587). No heterogeneity across these trials was detected (p =0.3111,I2 = 0.16%).
Data from 3 (among 7) trials evaluating target-vessel revascularization were available.When pooled together, there was no statistically significant difference between the groups intarget-vessel revascularization, with a RR of 0.75 (95% CI 0.51 to 1.09, p=0.1319). No hetero-geneity across these trials was detected (p =0.4456, I2 = 0.00%).
3.2. META-ANALYSIS RESULTS 57
All the 7 studies had extractable data about the number of participants with target lesionrevascularisation . When pooled together, there was no statistically significant differencebetween the groups in target lesion revascularisation , with a RR of 0.84 (95% CI 0.65 to 1.07,p=0.1531). No heterogeneity across these trials was detected (p =0.6239, I2 = 0.00%).
Only one of the 7 studies eligible for this comparison provided data on CABG. No statisti-cally significant difference between the groups was found in CABG, with a RR of 1.96 (95% CI0.07 to 57.80, p=0.6965).
Only one of the 7 studies eligible for this comparison provided data on in-lesion binaryrestenosis . No statistically significant difference between the groups was found in in-lesionbinary restenosis , with a RR of 0.88 (95% CI 0.67 to 1.16, p=0.3591).
Only one of the 7 studies eligible for this comparison provided data on angiographicrestenosis . No statistically significant difference between the groups was found in angiographicrestenosis , with a RR of 0.86 (95% CI 0.62 to 1.19, p=0.3692).
Table 3.2: Results details - Unparticular patients - comparison versus paclitaxel eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
CoStar stent versus paclitaxel eluting stent
All cause death RR=0.69 [0.20;2.39] 0.5618 1.0000 (I=0.00) 1 1675
MI (fatal and non fatal) RR=1.47 [0.82;2.65] 0.1946 1.0000 (I=0.00) 1 1675
MACE RR=1.61 [1.16;2.23] 0.0045 1.0000 (I=1.00) 1 1675
target-vessel revascularization RR=1.91 [1.27;2.89] 0.0021 1.0000 (I=0.00) 1 1675
Stent thrombosis (any, end offollow up)
RR=4.16 [0.50;34.49] 0.1863 1.0000 (I=0.00) 1 1675
late stent thrombosis (31days -1year)
RR=0.69 [0.04;11.07] 0.7958 1.0000 (I=0.00) 1 1675
Rapamycin eluting stent versus paclitaxel eluting stent
All cause death RR=0.67 [0.11;3.95] 0.6552 1.0000 (I=0.00) 1 450
Stent thrombosis (any, end offollow up)
RR=2.00 [0.18;21.90] 0.5703 1.0000 (I=0.00) 1 450
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.98 [0.64;1.50] 0.9272 0.6672 (I=0.00) 7 6075
cardiac death RR=0.85 [0.34;2.12] 0.7231 0.2939 (I=0.18) 3 4463
MI (fatal and non fatal) RR=0.79 [0.59;1.07] 0.1298 0.9989 (I=0.00) 7 6075
MACE RR=0.77 [0.59;1.01] 0.0587 0.3111 (I=0.16) 4 4875
target-vessel revascularization RR=0.75 [0.51;1.09] 0.1319 0.4456 (I=0.00) 3 4463
target lesion revascularisation RR=0.84 [0.65;1.07] 0.1531 0.6239 (I=0.00) 7 6075
CABG RR=1.96 [0.07;57.80] 0.6965 1.0000 (I=0.00) 1 202
in-lesion binary restenosis RR=0.88 [0.67;1.16] 0.3591 1.0000 (I=0.00) 1 1911
Stent thrombosis (any, end offollow up)
RR=0.82 [0.57;1.20] 0.3108 0.6992 (I=0.00) 7 6038
4y stent thrombosis (ARC) RR=0.73 [0.49;1.06] 0.0995 0.6547 (I=0.00) 7 6075
Acute stent thrombosis(<=24h)
RR=0.49 [0.09;2.66] 0.4079 1.0000 (I=0.00) 1 1353
sub acute stent thrombosis(1-30 days)
RR=0.42 [0.11;1.61] 0.2063 1.0000 (I=0.00) 1 1353
late stent thrombosis (31days -1year)
RR=0.24 [0.01;5.41] 0.3728 1.0000 (I=0.00) 1 1353
angiographic restenosis RR=0.86 [0.62;1.19] 0.3692 1.0000 (I=0.00) 1 1911
58CHAPTER 3. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 3.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
CoStar stent versus paclitaxel eluting stent
Costar II,2008 5/989 5/686 0.69 [0.20;2.39]
Global p ass= 0.5618 0.69 [0.20;2.39]
Rapamycin eluting stent versus paclitaxel eluting stent
ISAR-TEST-1,2006 2/225 3/225 0.67 [0.11;3.95]
Global p ass= 0.6552 0.67 [0.11;3.95]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]
Han,2006 3/210 4/206 0.74 [0.17;3.25]
Zhang (SES vs PES),2006 8/246 7/203 0.94 [0.35;2.56]
REALITY,2006 16/684 9/669 1.74 [0.77;3.91]
SIRTAX (Windecker),2005 5/503 11/509 0.46 [0.16;1.31]
TAXi,2005 0/102 0/100 0.98 [0.02;48.93]
BASKET (vs paclitaxel),20 10/264 11/281 0.97 [0.42;2.24]
Global p ass= 0.9272 0.98 [0.64;1.50]
Het. between 7 trials p=0.6672 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 3.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]
REALITY,2006 10/684 7/669 1.40 [0.53;3.65]
SIRTAX (Windecker),2005 3/503 8/509 0.38 [0.10;1.42]
Global p ass= 0.7231 0.85 [0.34;2.12]
Het. between 3 trials p=0.2939 I2=0.18
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
3.2. META-ANALYSIS RESULTS 59
Figure 3.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
CoStar stent versus paclitaxel eluting stent
Costar II,2008 34/989 16/686 1.47 [0.82;2.65]
Global p ass= 0.1946 1.47 [0.82;2.65]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]
Han,2006 2/210 3/206 0.65 [0.11;3.87]
Zhang (SES vs PES),2006 7/246 9/203 0.64 [0.24;1.69]
REALITY,2006 35/684 40/669 0.86 [0.55;1.33]
SIRTAX (Windecker),2005 14/503 18/509 0.79 [0.40;1.57]
TAXi,2005 2/102 3/100 0.65 [0.11;3.83]
BASKET (vs paclitaxel),20 14/264 19/281 0.78 [0.40;1.53]
Global p ass= 0.1298 0.79 [0.59;1.07]
Het. between 7 trials p=0.9989 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 3.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
CoStar stent versus paclitaxel eluting stent
Costar II,2008 109/989 47/686 1.61 [1.16;2.23]
Global p ass= 0.0045 1.61 [1.16;2.23]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]
Zhang (SES vs PES),2006 19/225 21/187 0.75 [0.42;1.36]
REALITY,2006 73/684 76/669 0.94 [0.69;1.27]
SIRTAX (Windecker),2005 31/503 55/509 0.57 [0.37;0.87]
Global p ass= 0.0587 0.77 [0.59;1.01]
Het. between 4 trials p=0.3111 I2=0.16
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
60CHAPTER 3. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 3.5: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
CoStar stent versus paclitaxel eluting stent
Costar II,2008 80/989 29/686 1.91 [1.27;2.89]
Global p ass= 0.0021 1.91 [1.27;2.89]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]
REALITY,2006 14/684 12/669 1.14 [0.53;2.45]
SIRTAX (Windecker),2005 30/503 47/509 0.65 [0.42;1.00]
Global p ass= 0.1319 0.75 [0.51;1.09]
Het. between 3 trials p=0.4456 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 3.6: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 0/1065 0/1033 0.97 [0.02;48.84]
Han,2006 9/210 11/206 0.80 [0.34;1.90]
Zhang (SES vs PES),2006 14/246 16/203 0.72 [0.36;1.44]
REALITY,2006 41/684 41/669 0.98 [0.64;1.49]
SIRTAX (Windecker),2005 24/503 42/509 0.58 [0.36;0.94]
TAXi,2005 2/102 1/100 1.96 [0.18;21.28]
BASKET (vs paclitaxel),20 22/264 21/281 1.12 [0.63;1.98]
Global p ass= 0.1531 0.84 [0.65;1.07]
Het. between 7 trials p=0.6239 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
3.2. META-ANALYSIS RESULTS 61
Figure 3.7: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
TAXi,2005 1/102 0/100 1.96 [0.07;57.80]
Global p ass= 0.6965 1.96 [0.07;57.80]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 3.8: Forest’s plot for in-lesion binary restenosis
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
REALITY,2006 86/970 95/941 0.88 [0.67;1.16]
Global p ass= 0.3591 0.88 [0.67;1.16]
1.00.5 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
62CHAPTER 3. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 3.9: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
CoStar stent versus paclitaxel eluting stent
Costar II,2008 6/989 1/686 4.16 [0.50;34.49]
Global p ass= 0.1863 4.16 [0.50;34.49]
Rapamycin eluting stent versus paclitaxel eluting stent
ISAR-TEST-1,2006 2/225 1/225 2.00 [0.18;21.90]
Global p ass= 0.5703 2.00 [0.18;21.90]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 28/1065 30/1033 0.91 [0.54;1.50]
Han,2006 1/210 2/206 0.49 [0.04;5.37]
Zhang (SES vs PES),2006 2/225 3/187 0.55 [0.09;3.28]
REALITY,2006 5/684 13/669 0.38 [0.13;1.05]
SIRTAX (Windecker),2005 10/503 8/509 1.26 [0.50;3.18]
TAXi,2005 1/102 0/100 1.96 [0.07;57.80]
BASKET (vs paclitaxel),20 4/264 5/281 0.85 [0.23;3.14]
Global p ass= 0.3108 0.82 [0.57;1.20]
Het. between 7 trials p=0.6992 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 3.10: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
SORT OUT II,2008 19/1065 19/1033 0.97 [0.52;1.82]
Han,2006 1/210 2/206 0.49 [0.04;5.37]
Zhang (SES vs PES),2006 2/246 3/203 0.55 [0.09;3.26]
REALITY,2006 6/684 18/669 0.33 [0.13;0.82]
SIRTAX (Windecker),2005 12/503 15/509 0.81 [0.38;1.71]
TAXi,2005 2/102 2/100 0.98 [0.14;6.83]
BASKET (vs paclitaxel),20 4/264 5/281 0.85 [0.23;3.14]
Global p ass= 0.0995 0.73 [0.49;1.06]
Het. between 7 trials p=0.6547 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
3.2. META-ANALYSIS RESULTS 63
Figure 3.11: Forest’s plot for acute stent thrombosis (<=24h)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
REALITY,2006 2/684 4/669 0.49 [0.09;2.66]
Global p ass= 0.4079 0.49 [0.09;2.66]
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 3.12: Forest’s plot for sub acute stent thrombosis (1-30 days)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
REALITY,2006 3/684 7/669 0.42 [0.11;1.61]
Global p ass= 0.2063 0.42 [0.11;1.61]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 3.13: Forest’s plot for late stent thrombosis (31days - 1year)
Trial studied T. control T. RR [95%CI]
CoStar stent versus paclitaxel eluting stent
Costar II,2008 1/989 1/686 0.69 [0.04;11.07]
Global p ass= 0.7958 0.69 [0.04;11.07]
Sirolimus eluting stent versus paclitaxel eluting stent
REALITY,2006 0/684 2/669 0.24 [0.01;5.41]
Global p ass= 0.3728 0.24 [0.01;5.41]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
64 REFERENCES
Figure 3.14: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
REALITY,2006 63/970 71/941 0.86 [0.62;1.19]
Global p ass= 0.3692 0.86 [0.62;1.19]
1.00.5 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Krucoff MW, Kereiakes DJ, Petersen JL, Mehran R, Hasselblad V, Lansky AJ, Fitzgerald PJ, Garg J,Turco MA, Simonton CA 3rd, Verheye S, Dubois CL, Gammon R, Batchelor WB, O’Shaughnessy CD,Hermiller JB Jr, Schofer J, Buchbinder M, Wijns W. A novel bioresorbable polymer paclitaxel-elutingstent for the treatment of single and multivessel coronary disease: primary results of the COSTAR (CobaltChromium Stent With Antiproliferative for Restenosis) II study.. J Am Coll Cardiol 2008 Apr 22;51:1543-52[PMID=18420096]
[2] Wessely R, Kastrati A, Mehilli J, Dibra A, Pache J, Schmig A. Randomized trial of rapamycin- andpaclitaxel-eluting stents with identical biodegradable polymeric coating and design.. Eur Heart J 2007Nov;28:2720-5 [PMID=17921531]
[3] Mehilli J, Kastrati A, Wessely R, Dibra A, Hausleiter J, Jaschke B, Dirschinger J, Schmig A. Randomizedtrial of a nonpolymer-based rapamycin-eluting stent versus a polymer-based paclitaxel-eluting stent for thereduction of late lumen loss.. Circulation 2006;113:273-9 [PMID=16391155]
[4] Galloe AM.. prospective multi-center, large-scale, randomized trialof paclitaxel- and sirolimus-eluting stentsin real-world lesions. Annual Scientifi c Meeting of the Transcatheter CardiovascularTherapeutics; Wash-ington, DC; Oct 2227, 2006
[5] Galle AM, Thuesen L, Kelbaek H, Thayssen P, Rasmussen K, Hansen PR, Bligaard N, Saunamki K, JunkerA, Aare J, Abildgaard U, Ravkilde J, Engstrm T, Jensen JS, Andersen HR, Btker HE, Galatius S, KristensenSD, Madsen JK, Krusell LR, Abildstrm SZ, Step. Comparison of paclitaxel- and sirolimus-eluting stents ineveryday clinical practice: the SORT OUT II randomized trial.. JAMA 2008;299:409-16 [PMID=18230778]
[6] Han YL, Wang XZ, Jing QM, Wang SL, Ma YY, Luan B. [Comparison of Rapamycin and Paclitaxel elutingstent in patients with multi-vessel coronary disease]. Zhonghua Xin Xue Guan Bing Za Zhi 2006;34:123-6[PMID=16626577]
[7] Zhang Q, Zhang RY, Zhang JS, Hu J, Yang ZK, Ni J, Fang YH, Zhang X, Shen WF. One-year clinicaloutcomes of Chinese sirolimus-eluting stent in the treatment of unselected patients with coronary arterydisease.. Chin Med J (Engl) 2006;119:165-8 [PMID=16455001]
[8] Morice MC, Colombo A, Meier B, Serruys P, Tamburino C, Guagliumi G, Sousa E, Stoll HP. Sirolimus- vspaclitaxel-eluting stents in de novo coronary artery lesions: the REALITY trial: a randomized controlledtrial.. JAMA 2006;295:895-904 [PMID=16493102]
[9] Windecker S, Remondino A, Eberli FR, Jni P, Rber L, Wenaweser P, Togni M, Billinger M, Tller D, SeilerC, Roffi M, Corti R, Stsch G, Maier W, Lscher T, Hess OM, Egger M, Meier B. Sirolimus-eluting andpaclitaxel-eluting stents for coronary revascularization.. N Engl J Med 2005;353:653-62 [PMID=16105989]
REFERENCES 65
[10] Goy JJ, Stauffer JC, Siegenthaler M, Benot A, Seydoux C. A prospective randomized comparison betweenpaclitaxel and sirolimus stents in the real world of interventional cardiology: the TAXi trial.. J Am CollCardiol 2005;45:308-11 [PMID=15653032]
[11] Berger A, Stauffer JC, Seydoux C, Siegenthaler M, Benot A, Goy JJ. Three-year follow-up of the firstprospective randomized comparison between paclitaxel and sirolimus stents: the TAXi-LATE trial.. CatheterCardiovasc Interv 2007 Aug 1;70:163-6 [PMID=17630653]
[12] Kaiser C, Brunner-La Rocca HP, Buser PT, Bonetti PO, Osswald S, Linka A, Bernheim A, Zutter A,Zellweger M, Grize L, Pfisterer ME. Incremental cost-effectiveness of drug-eluting stents compared with athird-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitts Trial(BASKET).. Lancet 2005;366:921-9 [PMID=16154019]
66 CHAPTER 4. DETAILS FOR COMPARISON VERSUS SIROLIMUS ELUTING STENT
4 Detailed results for comparison versus sirolimus
eluting stent in unparticular patients
4.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus sirolimuseluting stent
A total of 2 RCTs which randomized 2143 patients were identified: 1 trial compared biolimuseluting stent with sirolimus eluting stent and 1 trial compared zotarolimus eluting stent withsirolimus eluting stent (see 4.1 page 67).
The average study size was 1071 patients per arm (range 109 to 857 per arm). The firststudy was published in 2006, and the last study was published in 2008.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target lesion revascularisation data was reported in 2 trials; 2 trials reported data on MI(fatal and non fatal); 2 trials reported data on MACE; 2 trials reported data on angiographicrestenosis ; 2 trials reported data on All cause death; 1 trials reported data on target-vesselrevascularization; 1 trials reported data on in-lesion binary restenosis ; 1 trials reported data oncardiac death; 1 trials reported data on CABG; 2 trials reported data on Stent thrombosis (any,end of follow up); and 1 trials reported data on late stent thrombosis (31days - 1year).
Following table 4.1 (page 67) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus sirolimus eluting stent.
4.1. AVAILABLE RCTS 67
Table
4.1
:M
ain
study
char
act
eris
tics
-U
npar
ticu
lar
pat
ients
-co
mpar
ison
vers
us
siro
lim
us
eluti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Bio
lim
us
elu
ting
stentvers
us
siro
lim
us
elu
ting
stent
LE
AD
ER
S,
2008
[1]
n=
857
vs.
850
pati
ents
aged
18
yea
rsor
old
erw
ith
chro
nic
stable
coro
nary
art
ery
dis
ease
or
acu
teco
ronary
syndro
mes
Bio
Matr
ixII
I(b
iolim
us-
eluti
ng
sten
tw
ithbio
deg
radable
poly
mer
)vs.
Cypher
SE
LE
CT
(sir
olim
us-
eluti
ng
sten
tw
ith
dura
ble
poly
mer
)m
ult
ives
sel
trea
tmen
t:34.2
op
enass
esso
r-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:ca
rdia
cdea
th,
MI,
tar-
get
ves
sel
reva
scula
risa
tion
10
centr
es,
Euro
pe
Zota
rolim
us
elu
ting
stentvers
us
siro
lim
us
elu
ting
stent
EN
DE
AV
OR
III,
2006
[2,
3]
n=
327
vs.
109
single
de
nov
ole
sions
innati
ve
coro
nary
art
erie
s2.5
-3.5
mm
india
met
erA
BT
-578
coate
dE
ndea
vor
vs.
Cypher
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:in
-seg
men
tla
telu
men
loss
29
centr
es,
US
68 CHAPTER 4. DETAILS FOR COMPARISON VERSUS SIROLIMUS ELUTING STENT
4.2 Meta-analysis results
The results are detailed in table 4.2 (page 69). This table is followed by the Forest’s plotcorresponding to each endpoint.
Biolimus eluting stent versus sirolimus eluting stent
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between biolimus eluting stent andsirolimus eluting stent, with a RR of 0.91 (95%CI 0.51 to 1.61, p=0.7437) in favour of biolimuseluting stent. In other words, all cause death was slightly lower in the biolimus eluting stentgroup , but this was not statistically significant.
The single study eligible for this comparison provided data on cardiac death. No statis-tically significant difference between the groups was found in cardiac death, with a RR of 0.66(95% CI 0.34 to 1.29, p=0.2259).
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 1.25 (95% CI 0.83 to 1.88, p=0.2925).
The single study eligible for this comparison provided data on MACE. No statisticallysignificant difference between the groups was found in MACE, with a RR of 0.92 (95% CI 0.69to 1.23, p=0.5822).
The single study eligible for this comparison provided data on target-vessel revascular-ization. No statistically significant difference between the groups was found in target-vesselrevascularization, with a RR of 0.80 (95% CI 0.53 to 1.22, p=0.2994).
The single study eligible for this comparison provided data on target lesion revascular-isation . No statistically significant difference between the groups was found in target lesionrevascularisation , with a RR of 0.87 (95% CI 0.57 to 1.35, p=0.5400).
The single study eligible for this comparison provided data on CABG. No statisticallysignificant difference between the groups was found in CABG, with a RR of 0.50 (95% CI 0.20to 1.22, p=0.1276).
The single study eligible for this comparison provided data on angiographic restenosis .No statistically significant difference between the groups was found in angiographic restenosis ,with a RR of 0.64 (95% CI 0.33 to 1.24, p=0.1833).
Zotarolimus eluting stent versus sirolimus eluting stent
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between zotarolimus eluting stentand sirolimus eluting stent, with a RR of 0.70 (95%CI 0.06 to 7.65, p=0.7700) in favour ofzotarolimus eluting stent. In other words, all cause death was slightly lower in the zotarolimuseluting stent group , but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).The analysis detected a statistically significant difference in favor of zotarolimus eluting stent inMI (fatal and non fatal), with a RR of 0.18 (95% CI 0.03 to 0.96, p=0.0451).
The single study eligible for this comparison provided data on MACE. No statisticallysignificant difference between the groups was found in MACE, with a RR of 0.97 (95% CI 0.47to 2.02, p=0.9398).
The single study eligible for this comparison provided data on target lesion revascular-isation . No statistically significant difference between the groups was found in target lesionrevascularisation , with a RR of 1.84 (95% CI 0.64 to 5.24, p=0.2549).
The single study eligible for this comparison provided data on in-lesion binary restenosis. The analysis detected a statistically significant difference in favor of sirolimus eluting stent inin-lesion binary restenosis , with a RR of 2.75 (95% CI 1.00 to 7.56, p=0.0499).
4.2. META-ANALYSIS RESULTS 69
The single study eligible for this comparison provided data on angiographic restenosis .The analysis detected a statistically significant difference in favor of sirolimus eluting stent inangiographic restenosis , with a RR of 4.33 (95% CI 1.05 to 17.91, p=0.0429).
Table 4.2: Results details - Unparticular patients - comparison versus sirolimus eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
Biolimus eluting stent versus sirolimus eluting stent
All cause death RR=0.91 [0.51;1.61] 0.7437 1.0000 (I=0.00) 1 1707
cardiac death RR=0.66 [0.34;1.29] 0.2259 1.0000 (I=0.00) 1 1707
MI (fatal and non fatal) RR=1.25 [0.83;1.88] 0.2925 1.0000 (I=0.00) 1 1707
MACE RR=0.92 [0.69;1.23] 0.5822 1.0000 (I=0.00) 1 1707
target-vessel revascularization RR=0.80 [0.53;1.22] 0.2994 1.0000 (I=0.00) 1 1707
target lesion revascularisation RR=0.87 [0.57;1.35] 0.5400 1.0000 (I=0.00) 1 1707
CABG RR=0.50 [0.20;1.22] 0.1276 1.0000 (I=0.00) 1 1707
Stent thrombosis (any, end offollow up)
RR=1.15 [0.63;2.11] 0.6547 1.0000 (I=0.00) 1 1707
late stent thrombosis (31days -1year)
RR=0.99 [0.25;3.95] 0.9907 1.0000 (I=0.00) 1 1707
angiographic restenosis RR=0.64 [0.33;1.24] 0.1833 1.0000 (I=0.00) 1 484
Zotarolimus eluting stent versus sirolimus eluting stent
All cause death RR=0.70 [0.06;7.65] 0.7700 1.0000 (I=0.00) 1 432
MI (fatal and non fatal) RR=0.18 [0.03;0.96] 0.0451 1.0000 (I=0.00) 1 429
MACE RR=0.97 [0.47;2.02] 0.9398 1.0000 (I=0.00) 1 432
target lesion revascularisation RR=1.84 [0.64;5.24] 0.2549 1.0000 (I=1.00) 1 432
in-lesion binary restenosis RR=2.75 [1.00;7.56] 0.0499 1.0000 (I=0.00) 1 376
Stent thrombosis (any, end offollow up)
RR=0.35 [0.01;17.54] 0.5991 1.0000 (I=0.00) 1 432
angiographic restenosis RR=4.33 [1.05;17.91] 0.0429 1.0000 (I=0.00) 1 376
Figure 4.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 22/857 24/850 0.91 [0.51;1.61]
Global p ass= 0.7437 0.91 [0.51;1.61]
Zotarolimus eluting stent versus sirolimus eluting stent
ENDEAVOR III,2006 2/320 1/112 0.70 [0.06;7.65]
Global p ass= 0.7700 0.70 [0.06;7.65]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
70 CHAPTER 4. DETAILS FOR COMPARISON VERSUS SIROLIMUS ELUTING STENT
Figure 4.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 14/857 21/850 0.66 [0.34;1.29]
Global p ass= 0.2259 0.66 [0.34;1.29]
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 4.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 49/857 39/850 1.25 [0.83;1.88]
Global p ass= 0.2925 1.25 [0.83;1.88]
Zotarolimus eluting stent versus sirolimus eluting stent
ENDEAVOR III,2006 2/316 4/113 0.18 [0.03;0.96]
Global p ass= 0.0451 0.18 [0.03;0.96]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
4.2. META-ANALYSIS RESULTS 71
Figure 4.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 78/857 84/850 0.92 [0.69;1.23]
Global p ass= 0.5822 0.92 [0.69;1.23]
Zotarolimus eluting stent versus sirolimus eluting stent
ENDEAVOR III,2006 25/320 9/112 0.97 [0.47;2.02]
Global p ass= 0.9398 0.97 [0.47;2.02]
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 4.5: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 38/857 47/850 0.80 [0.53;1.22]
Global p ass= 0.2994 0.80 [0.53;1.22]
1.00.5 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
72 CHAPTER 4. DETAILS FOR COMPARISON VERSUS SIROLIMUS ELUTING STENT
Figure 4.6: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 37/857 42/850 0.87 [0.57;1.35]
Global p ass= 0.5400 0.87 [0.57;1.35]
Zotarolimus eluting stent versus sirolimus eluting stent
ENDEAVOR III,2006 21/320 4/112 1.84 [0.64;5.24]
Global p ass= 0.2549 1.84 [0.64;5.24]
1.00.5 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 4.7: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 7/857 14/850 0.50 [0.20;1.22]
Global p ass= 0.1276 0.50 [0.20;1.22]
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 4.8: Forest’s plot for in-lesion binary restenosis
Trial studied T. control T. RR [95%CI]
Zotarolimus eluting stent versus sirolimus eluting stent
ENDEAVOR III,2006 33/282 4/94 2.75 [1.00;7.56]
Global p ass= 0.0499 2.75 [1.00;7.56]
1.0 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
4.2. META-ANALYSIS RESULTS 73
Figure 4.9: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 22/857 19/850 1.15 [0.63;2.11]
Global p ass= 0.6547 1.15 [0.63;2.11]
Zotarolimus eluting stent versus sirolimus eluting stent
ENDEAVOR III,2006 0/320 0/112 0.35 [0.01;17.54]
Global p ass= 0.5991 0.35 [0.01;17.54]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 4.10: Forest’s plot for late stent thrombosis (31days - 1year)
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 4/857 4/850 0.99 [0.25;3.95]
Global p ass= 0.9907 0.99 [0.25;3.95]
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
74 REFERENCES
Figure 4.11: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Biolimus eluting stent versus sirolimus eluting stent
LEADERS,2008 14/253 20/231 0.64 [0.33;1.24]
Global p ass= 0.1833 0.64 [0.33;1.24]
Zotarolimus eluting stent versus sirolimus eluting stent
ENDEAVOR III,2006 26/282 2/94 4.33 [1.05;17.91]
Global p ass= 0.0429 4.33 [1.05;17.91]
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Windecker S, Serruys PW, Wandel S, Buszman P, Trznadel S, Linke A, Lenk K, Ischinger T, Klauss V, EberliF, Corti R, Wijns W, Morice MC, di Mario C, Davies S, van Geuns RJ, Eerdmans P, van Es GA, MeierB, Jni P. Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durablepolymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial.. Lancet 2008 Aug31;: [PMID=18765162]
[2] Miyazawa A, Ako J, Hongo Y, Hur SH, Tsujino I, Courtney BK, Hassan AH, Kandzari DE, Honda Y,Fitzgerald PJ, , . Comparison of vascular response to zotarolimus-eluting stent versus sirolimus-eluting stent:intravascular ultrasound results from ENDEAVOR III.. Am Heart J 2008;155:108-13. [PMID=18082499]
[3] Kandzari DE, Leon MB, Popma JJ, Fitzgerald PJ, O’Shaughnessy C, Ball MW, Turco M, ApplegateRJ, Gurbel PA, Midei MG, Badre SS, Mauri L, Thompson KP, LeNarz LA, Kuntz RE. Comparison ofzotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a random-ized controlled trial.. J Am Coll Cardiol 2006;48:2440-7 [PMID=17174180]
75
5 Ongoing studies of Unparticular patients
5.1 List of ongoing trials
A total of 19 studies were still ongoing at the date of this report. A list of these ongoing studieswith a brief description is given table 5.1.
Table 5.1: Ongoing studies for Unparticular patients
Study Description
BASKET-PROVE (2008)[1]
Cypher vs. Vision
GENESIS Trial CP-01 (0)[] NCT00322569
Corio Pimecrolimus vs. CoStar
patients with de novo lesions of the native coronary arteries
ZoMaxx phase 2 (0)[] NCT00140101
ZoMaxx drug-eluting stent vs. TAXUS Express2
de Novo Coronary Artery Lesions
PROTECT (0)[] NCT00476957
Medtronic Endeavor Zotarolimus Eluting Coronary Stent System vs.Cordis Cypher Sirolimus-eluting Coronary Stent
unselected patients
PEPCAD III (0)[] NCT00473499
DEBlue stent vs. Cypher
stenoses in native coronary arteries
MIDCAB Versus DES inProximal LAD Lesions (0)[] NCT00299429
sirolimus-coated stent vs. minimally invasive bypass surgery
patients with isolated proximal left anterior descending coronary arter-ies
RES-ELUTION (0)[] NCT00606333
Conor Cobalt Chromium Sirolimus-eluting Coronary Stent System vs.TAXUS Liberte Paclitaxel-eluting Coronary Stent System
De Novo Native Coronary Artery Lesions
FEMH-93005 (0)[] NCT00190099
vs.
ZEST (0)[] NCT00418067
ABT 578-eluting balloon expandable stent (Medtronic) vs. CYPHERor TAXUS Libert
real-world practice
TRIAS-Low-Risk (0)[]
vs.
COMBAT (0)[]
PCI vs. CABG
Korean Randomized Study(0)[]
PCI vs. CABG
Munich Study (0)[]
sirolimus vs. CABG
REVASCULARIZE (0)[]
PCI vs. CABG
SORT OUT IV (0)[] NCT00552877
Xience V vs. Cypher Select+
unselected patients with coronary artery disease
PERSEUS WH (0)[] NCT00484315
TAXUS ElementTM vs. TAXUS Express 2
De Novo Coronary Artery Lesions
continued...
76 REFERENCES
Study Description
FRE-RACE (0)[] NCT00130546
Cypher select vs. Taxus
de novo native coronary lesions with two or more coronary arterystenoses
ENDEAVOR IV (0)[2] NCT00217269
Endeavor vs. Taxus
single de novo lesions in native coronary arteries with a reference vesseldiameter (RVD) of 2.5-3.5 mm
SPIRIT IV (0)[] NCT00307047
XIENCE V Everolimus Eluting Coronary Stent System vs. TAXUSEXPRESS2 Paclitaxel Eluting Coronary Stent System (TAXUS).
subjects with reference vessel diameters (RVD) 2.5 mm to 4.25 mm andlesion lengths <= 28 mm
References
[1] Pfisterer M, Bertel O, Bonetti PO, Brunner-La Rocca HP, Eberli FR, Erne P, Galatius S, Hornig B, KiowskiW, Pachinger O, Pedrazzini G, Rickli H, De Servi S, Kaiser C, , . Drug-eluting or bare-metal stents forlarge coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: studyprotocol and design.. Am Heart J 2008;155:609-14. [PMID=18371466]
[2] Leon MB. Endeavor Clinical Program Overview,. FDA Advisory Panel, October 10th, 2007
Part II
Diabetic patients
77
78
79
6 Overview of available evidence for diabetic
patients
A total of 18 RCTs which randomized 3143 patients were identified. (see tables 6.1 to 6.3 )In all, 11 reports concerned comparison versus bare-metal stent , 6 the comparison versus
paclitaxel eluting stent and 1 the comparison versus rapamycin eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 7 (page 92)
for comparison versus bare-metal stent, in section 8 (page 103 ) for comparison versus paclitaxeleluting stent and in section 9 (page 110 ) for comparison versus rapamycin eluting stent.
The average study size was 174 patients per arm (range 19 to 192 per arm). The first studywas published in 2003, and the last study was published in 2008. 5 trials were double blind and8 were open-label in design. All included studies were reported in English language. We did notfound any unpublished trial.
80 CHAPTER 6. OVERVIEW OF AVAILABLE EVIDENCE FOR DIABETIC PATIENTS
Table
6.1
:M
ain
study
char
acte
rist
ics
-D
iabet
icpat
ients
-co
mpar
ison
vers
us
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
TA
XU
SV
I(d
iab
etic
s),
2005
[1]
TA
XU
Svs.
Expre
ss2
sten
t39
vs.
50
double
-blind
Para
llel
gro
ups
TV
RE
uro
pe
TA
XU
SV
(dia
bet
ics)
,2005
[2]
TA
XU
Svs.
BM
S178
vs.
171
double
-blind
Para
llel
gro
ups
TV
RU
nit
edSta
tes
TA
XU
SIV
(dia
bet
ics)
,2005
[3]
TA
XU
Svs.
EX
PR
ESS
155
vs.
163
double
-blind
Para
llel
gro
ups
TV
RU
nit
edSta
tes
TA
XU
SII
(dia
bet
ics)
,2003
[4]
TA
XU
Svs.
NIR
sten
t37
vs.
41
double
-blind
Para
llel
gro
ups
Neo
inti
mal
pro
life
rati
on
Euro
pe
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
DE
SSE
RT
,2008
[5]
Cypher
andC
ypher
Sel
ect
vs.
Sonic
(Cord
is)
75
vs.
75
single
-blind
Para
llel
gro
ups
in-s
tent
late
loss
Italy
SC
OR
PIU
S,
2007
[6,
7]
Cypher
vs.
Bx-V
eloci
ty98
vs.
102
op
enP
ara
llel
gro
ups
Late
lum
enlo
ssG
erm
any
SE
S-S
MA
Rt
(dia
bet
ics)
,2005
[8]
Cypher
vs.
Bx
Sonic
29
vs.
45
single
-blind
Para
llel
gro
ups
Bin
ary
rest
enosi
sIt
aly
DE
CO
DE
,2005
[9]
CY
PH
ER
(Up
to3
sten
tsp
erpati
ent
wer
eallow
ed)
vs.
Bx
VE
LO
CIT
Y(U
pto
3st
ents
per
pati
ent
wer
eallow
ed)
54
vs.
29
op
enP
ara
llel
gro
ups
Late
lum
enlo
ssU
S,
Asi
a/P
aci
fic
DIA
BE
TE
S,
2005
[10,
11]
Cypher
vs.
Bx
Vel
oci
ty/Sonic
80
vs.
80
op
enP
ara
llel
gro
ups
Late
lum
enlo
ssSpanis
h
Rav
el(d
iab
etic
s),
2004
[12]
coate
dB
xvel
oci
tyvs.
Bx
VE
LO
CIT
Y19
vs.
25
NA
Para
llel
gro
ups
NA
Euro
pe
SIR
IUS
(dia
bet
ics)
,2003
[13,
14]
SE
Svs.
BM
S131
vs.
148
double
-blind
Para
llel
gro
ups
NA
US
81
Table
6.2
:M
ain
study
chara
cter
isti
cs-
Dia
bet
icpat
ients
-co
mpar
ison
vers
us
pacl
itaxel
eluti
ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
paclita
xel
elu
ting
stent
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Tom
ai,
2008
[1]
siro
lim
us-
eluti
ng
sten
tvs.
pacl
itaxel
-elu
ting
sten
t
60
vs.
60
NA
Cro
ssov
erin
-ste
nt
late
lum
inal
loss
Italy
Kim
,2008
[2]
Cypher
vs.
Taxus
85
vs.
84
op
enP
ara
llel
gro
ups
late
lum
enlo
ssK
ore
a
RE
AL
ITY
(dia
bet
ics)
,2006
[3]
SE
Svs.
PE
S187
vs.
192
op
enP
ara
llel
gro
ups
NA
worl
dw
ide
SIR
TA
Xdia
bet
ics,
2005
[4,
5]
Cypher
vs.
Taxus
108
vs.
93
single
-blind
Para
llel
gro
ups
card
iac
dea
th,
AM
I,T
LR
Sw
itze
rland
ISA
R-D
IAB
ET
ES,
2005
[6]
Taxus
vs.
Cypher
125
vs.
125
op
enP
ara
llel
gro
ups
Late
lum
enlo
ssG
erm
any
TA
xi
(dia
bet
ics)
,0
[]unpublish
edSE
Svs.
PE
S33
vs.
36
op
enP
ara
llel
gro
ups
NA
Sw
itze
rland
82 CHAPTER 6. OVERVIEW OF AVAILABLE EVIDENCE FOR DIABETIC PATIENTS
Table
6.3
:M
ain
study
chara
cter
isti
cs-
Dia
bet
icpat
ients
-co
mpar
ison
vers
us
rapam
yci
nel
uti
ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
rapam
ycin
elu
ting
stent
Paclita
xelelu
ting
stentvers
us
rapam
ycin
elu
ting
stent
ISA
R-t
est
(dia
bet
ics)
,2006
[1]
Taxus
vs.
rapam
yci
nst
ent
73
vs.
58
op
enP
ara
llel
gro
ups
NA
ger
many
6.1. MAIN RESULTS FOR DIABETIC PATIENTS 83
6.1 Main results for Diabetic patients
The meta-analysis of the available trials provide the results listed in tables 6.4 to 6.6 (page 83)and in the following graphs.
6.2 comparison versus bare-metal stent - summary of results
Paclitaxel eluting stent was superior to bare-metal stent in terms of target lesion revas-cularisation (RR=0.40, 95% CI 0.27 to 0.60, p=0.0000, 4 trials) and angiographic restenosis(RR=0.17, 95% CI 0.08 to 0.37, p=0.0000, 3 trials) .
Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.46,95% CI 0.32 to 0.67, p=0.0000, 3 trials) , 2 yr MACE (RR=0.31, 95% CI 0.16 to 0.59, p=0.0000,1 trial) , target-vessel revascularization (RR=0.25, 95% CI 0.10 to 0.61, p=0.0026, 1 trial) , 2yr TLR (RR=0.22, 95% CI 0.10 to 0.50, p=0.0000, 1 trial) , target lesion revascularisation(RR=0.24, 95% CI 0.13 to 0.44, p=0.0000, 5 trials) and angiographic restenosis (RR=0.18, 95%CI 0.11 to 0.29, p=0.0000, 4 trials) .However, no significant difference was found on all causedeath (RR=0.83, 95% CI 0.21 to 3.34, p=0.7950, 3 trials) , MI (fatal and non fatal) (RR=0.80,95% CI 0.42 to 1.55, p=0.5128, 2 trials) and CABG (RR=1.03, 95% CI 0.02 to 51.15, p=0.9884,1 trial) .
6.3 comparison versus paclitaxel eluting stent - summary ofresults
No significant difference was found between sirolimus eluting stent and paclitaxel elutingstent in terms of all cause death (RR=0.71, 95% CI 0.23 to 2.21, p=0.5568, 2 trials) , MI(fatal and non fatal) (RR=1.50, 95% CI 0.43 to 5.25, p=0.5297, 2 trials) , MACE (RR=1.64,95% CI 0.29 to 9.19, p=0.5759, 1 trial) , target lesion revascularisation (RR=0.72, 95% CI 0.40to 1.29, p=0.2697, 5 trials) , CABG (RR=0.99, 95% CI 0.02 to 49.23, p=0.9953, 1 trial) andangiographic restenosis (RR=0.40, 95% CI 0.08 to 1.98, p=0.2591, 1 trial) .
6.4 comparison versus rapamycin eluting stent - summary ofresults
Data were insufficient to compare Paclitaxel eluting stent to rapamycin eluting stent.There was an eligible trial but it did not provided sufficient information about the endpointsconsidered by this meta-analysis.
Table 6.4: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Paclitaxel eluting stent versus bare-metal stent
target lesion revascularisation RR=0.40 0.27;0.60 0.0000 0.3757 (0.03) 4 834
angiographic restenosis RR=0.17 0.08;0.37 0.0000 0.9222 (0.00) 3 485
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.83 0.21;3.34 0.7950 0.3992 (0.00) 3 295
MI (fatal and non fatal) RR=0.80 0.42;1.55 0.5128 0.9635 (0.00) 2 212
MACE RR=0.46 0.32;0.67 0.0000 0.3847 (0.00) 3 372
continued...
84 CHAPTER 6. OVERVIEW OF AVAILABLE EVIDENCE FOR DIABETIC PATIENTS
Endpoint Effect 95% CI p ass p het k n
2 yr MACE RR=0.31 0.16;0.59 0.0000 1.0000 (0.00) 1 158
target-vessel revascularization RR=0.25 0.10;0.61 0.0026 1.0000 (0.00) 1 138
2 yr TLR RR=0.22 0.10;0.50 0.0000 1.0000 (1.00) 1 158
target lesion revascularisation RR=0.24 0.13;0.44 0.0000 0.1320 (0.43) 5 499
CABG RR=1.03 0.02;51.15 0.9884 1.0000 (0.00) 1 138
Stent thrombosis (any, end offollow up)
RR=0.80 0.16;4.08 0.7916 0.9641 (0.00) 3 295
Acute stent thrombosis(<=24h)
RR=1.03 0.02;51.15 0.9884 1.0000 (0.00) 1 138
sub acute stent thrombosis(1-30 days)
RR=1.03 0.09;11.21 0.9820 0.5687 (0.00) 2 296
late stent thrombosis (31days -1year)
RR=0.51 0.05;5.60 0.5849 0.9988 (0.00) 2 296
angiographic restenosis RR=0.18 0.11;0.29 0.0000 0.4447 (0.00) 4 422
Table 6.5: Summary of all results for comparison versus paclitaxel eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.71 0.23;2.21 0.5568 0.7985 (0.00) 2 419
MI (fatal and non fatal) RR=1.50 0.43;5.25 0.5297 0.7407 (0.00) 2 419
MACE RR=1.64 0.29;9.19 0.5759 1.0000 (0.00) 1 69
target lesion revascularisation RR=0.72 0.40;1.29 0.2697 0.2287 (0.29) 5 1068
CABG RR=0.99 0.02;49.23 0.9953 1.0000 (0.00) 1 169
Stent thrombosis (any, end offollow up)
RR=0.25 0.01;5.49 0.3791 1.0000 (0.00) 1 250
4y stent thrombosis (ARC) RR=0.25 0.01;5.49 0.3791 1.0000 (0.00) 1 250
late stent thrombosis (31days -1year)
RR=0.41 0.11;1.51 0.1790 0.5890 (0.00) 3 830
angiographic restenosis RR=0.40 0.08;1.98 0.2591 1.0000 (1.00) 1 169
Table 6.6: Summary of all results for comparison versus rapamycin eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Paclitaxel eluting stent versus rapamycin eluting stent
No data were presented in the trial identified
6.4. COMPARISON VERSUS RAPAMYCIN ELUTING STENT - SUMMARY OF RESULTS85
Figure 6.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.83 [0.21;3.34] .80 3 295 .40 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.71 [0.23;2.21] .56 2 419 .80 0.00
comparison versus rapamycin eluting stent
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 6.2: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.80 [0.42;1.55] .51 2 212 .96 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
1.50 [0.43;5.25] .53 2 419 .74 0.00
comparison versus rapamycin eluting stent
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
86 CHAPTER 6. OVERVIEW OF AVAILABLE EVIDENCE FOR DIABETIC PATIENTS
Figure 6.3: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.46 [0.32;0.67] .00 3 372 .38 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
1.64 [0.29;9.19] .58 1 69 1.00 0.00
comparison versus rapamycin eluting stent
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 6.4: Forest’s plot for 2 yr MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.31 [0.16;0.59] .00 1 158 1.00 0.00
comparison versus paclitaxel eluting stent
comparison versus rapamycin eluting stent
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
6.4. COMPARISON VERSUS RAPAMYCIN ELUTING STENT - SUMMARY OF RESULTS87
Figure 6.5: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.25 [0.10;0.61] .00 1 138 1.00 0.00
comparison versus paclitaxel eluting stent
comparison versus rapamycin eluting stent
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 6.6: Forest’s plot for 2 yr TLR
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.22 [0.10;0.50] .00 1 158 1.00 1.00
comparison versus paclitaxel eluting stent
comparison versus rapamycin eluting stent
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
88 CHAPTER 6. OVERVIEW OF AVAILABLE EVIDENCE FOR DIABETIC PATIENTS
Figure 6.7: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.40 [0.27;0.60] .00 4 834 .38 0.03
Sirolimus eluting stent versus bare-metalstent
0.24 [0.13;0.44] .00 5 499 .13 0.43
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.72 [0.40;1.29] .27 5 1068 .23 0.29
comparison versus rapamycin eluting stent
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 6.8: Forest’s plot for CABG
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
1.03 [0.02;51.15] .99 1 138 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.99 [0.02;49.23] 1.00 1 169 1.00 0.00
comparison versus rapamycin eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
6.4. COMPARISON VERSUS RAPAMYCIN ELUTING STENT - SUMMARY OF RESULTS89
Figure 6.9: Forest’s plot for stent thrombosis (any, end of follow up)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.80 [0.16;4.08] .79 3 295 .96 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.25 [0.01;5.49] .38 1 250 1.00 0.00
comparison versus rapamycin eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 6.10: Forest’s plot for 4y stent thrombosis (ARC)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.25 [0.01;5.49] .38 1 250 1.00 0.00
comparison versus rapamycin eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
90 CHAPTER 6. OVERVIEW OF AVAILABLE EVIDENCE FOR DIABETIC PATIENTS
Figure 6.11: Forest’s plot for acute stent thrombosis (<=24h)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
1.03 [0.02;51.15] .99 1 138 1.00 0.00
comparison versus paclitaxel eluting stent
comparison versus rapamycin eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 6.12: Forest’s plot for sub acute stent thrombosis (1-30 days)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
1.03 [0.09;11.21] .98 2 296 .57 0.00
comparison versus paclitaxel eluting stent
comparison versus rapamycin eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
6.4. COMPARISON VERSUS RAPAMYCIN ELUTING STENT - SUMMARY OF RESULTS91
Figure 6.13: Forest’s plot for late stent thrombosis (31days - 1year)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.51 [0.05;5.60] .58 2 296 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.41 [0.11;1.51] .18 3 830 .59 0.00
comparison versus rapamycin eluting stent
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 6.14: Forest’s plot for angiographic restenosis
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.17 [0.08;0.37] .00 3 485 .92 0.00
Sirolimus eluting stent versus bare-metalstent
0.18 [0.11;0.29] .00 4 422 .44 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.40 [0.08;1.98] .26 1 169 1.00 1.00
comparison versus rapamycin eluting stent
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
92 CHAPTER 7. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
7 Detailed results for comparison versus bare-metal
stent in diabetic patients
7.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
A total of 11 RCTs which randomized 1824 patients were identified: 4 trials comparedpaclitaxel eluting stent with bare-metal stent and 7 trials compared sirolimus eluting stent withbare-metal stent (see 7.1 page 93).
The average study size was 165 patients per arm (range 19 to 178 per arm). The first studywas published in 2003, and the last study was published in 2008. 5 trials were double blind and3 were open-label in design. All included studies were reported in English language. We did notfound any unpublished trial.
Target lesion revascularisation data was reported in 3 trials; 3 trials reported data on MACE;3 trials reported data on All cause death; 2 trials reported data on MI (fatal and non fatal); 2trials reported data on angiographic restenosis ; 1 trials reported data on target-vessel revascu-larization; 1 trials reported data on CABG; 1 trials reported data on 2 yr TLR ; 1 trials reporteddata on 2 yr MACE ; 3 trials reported data on Stent thrombosis (any, end of follow up); 2 trialsreported data on sub acute stent thrombosis (1-30 days); 2 trials reported data on late stentthrombosis (31days - 1year); and 1 trials reported data on Acute stent thrombosis (¡=24h).
Following table 7.1 (page 93) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus bare-metal stent.
7.1. AVAILABLE RCTS 93
Table
7.1
:M
ain
study
char
acte
rist
ics
-D
iabet
icpat
ients
-co
mpar
ison
vers
us
bare
-met
alst
ent
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
TA
XU
SV
I(d
iab
etic
s),
2005
[1]
n=
39
vs.
50
Dia
bet
icpati
ents
wit
hst
able
or
unst
able
AP
,si
lent
isch
aem
iaw
ith
long,
com
ple
xco
ronary
art
ery
lesi
ons
TA
XU
Svs.
Expre
ss2
sten
tdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:T
VR
44
centr
es,
Euro
pe
TA
XU
SV
(dia
bet
ics)
,2005
[2]
n=
178
vs.
171
Dia
bet
icpati
ents
wit
hst
able
or
unst
able
AP
,si
lent
isch
aem
iaw
ith
com
ple
xor
pre
vio
usl
yunst
udie
dle
sions
(req
uir
ing
2.2
5-m
m,
4.0
-mm
,and/or
mult
iple
sten
ts)
TA
XU
Svs.
BM
Sdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:T
VR
66
centr
es,
Unit
edSta
tes
TA
XU
SIV
(dia
bet
ics)
,2005
[3]
n=
155
vs.
163
Dia
bet
icpati
ents
wit
hst
able
or
unst
able
AP
,pro
voka
ble
isch
aem
iaw
ith
asi
ngle
,pre
vio
usl
yuntr
eate
dco
ronary
-art
ery
sten
osi
s(v
esse
ldia
met
er,
2.5
to3.7
5m
m;
lesi
on
length
,10
to28
mm
)
TA
XU
Svs.
EX
PR
ESS
double
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:T
VR
73
centr
es,
Unit
edSta
tes
TA
XU
SII
(dia
bet
ics)
,2003
[4]
n=
37
vs.
41
Dia
bet
icpati
ents
wit
hst
able
or
unst
able
AP
,si
lent
isch
aem
ia;
single
de
nov
ota
rget
lesi
on
wit
hes
tim
ate
dst
enosi
s>
50%
and
<99%
,
TA
XU
Svs.
NIR
sten
tdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:N
eoin
tim
al
pro
life
ra-
tion
38
centr
es,
Euro
pe
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
DE
SSE
RT
,2008
[5]
n=
75
vs.
75
de
nov
ole
sions
of
dia
bet
icpati
ents
trea
ted
wit
hin
sulin
and/or
ora
lanti
dia
bet
ics
for
>3
month
s
Cypher
andC
ypher
Sel
ect
vs.
Sonic
(Cord
is)
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:in
-ste
nt
late
loss
mult
icen
tre,
Italy
QC
Afo
llow
-up
dura
tion:
8m
onth
s
SC
OR
PIU
S,
2007
[6,
7]
n=
98
vs.
102
pati
ents
wit
hdia
bet
esand
de
nov
oco
ronary
art
ery
lesi
ons
Cypher
vs.
Bx-V
eloci
tyop
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:L
ate
lum
enlo
ss16
centr
es,
Ger
many
cont
inue
d...
94 CHAPTER 7. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
SE
S-S
MA
Rt
(dia
bet
ics)
,2005
[8]
n=
29
vs.
45
Dia
bet
icpati
ents
wit
hde
nov
ota
rget
lesi
on
<=
2.7
5m
min
dia
met
erin
anati
ve
coro
nary
art
ery
that
could
be
com
ple
tely
cover
edby
asi
ngle
sten
t(m
axim
um
length
33
mm
)
Cypher
vs.
Bx
Sonic
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s20
centr
es,
Italy
DE
CO
DE
,2005
[9]
n=
54
vs.
29
Sta
ble
or
unst
able
angin
ain
dia
bet
icpati
ents
wit
hw
ith
up
to2
de
nov
ole
sions
inup
to2
nati
ve
coro
nary
ves
sels
CY
PH
ER
(Up
to3
sten
tsp
erpati
ent
wer
eallow
ed)
vs.
Bx
VE
LO
CIT
Y(U
pto
3st
ents
per
pati
ent
wer
eallow
ed)
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:L
ate
lum
enlo
ssN
A,
US,
Asi
a/P
aci
fic
DIA
BE
TE
S,
2005
[10,
11]
n=
80
vs.
80
de
nov
ole
sions
innati
ve
coro
nary
art
erie
sin
1,
2,
or
3nati
ve
ves
sels
wit
hsy
mpto
ms
or
ob
ject
ive
evid
ence
of
isch
emia
;ves
sel
size
smaller
than
4.0
mm
Cypher
vs.
Bx
Vel
oci
ty/Sonic
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:L
ate
lum
enlo
ss4
centr
es,
Spanis
h
Rav
el(d
iab
etic
s),
2004
[12]
n=
19
vs.
25
sub
gro
ups
of
dia
bet
icpati
ents
wit
hde
nov
onati
ve
coro
nary
art
eryle
sions
2.5
to3.5
mm
india
met
erby
vis
uala
sses
smen
tth
at
could
be
cover
edby
an
18-m
mst
ent
coate
dB
xvel
oci
tyvs.
Bx
VE
LO
CIT
YN
AP
ara
llel
gro
ups
Pri
mary
endp
oin
t:,
Euro
pe
SIR
IUS
(dia
bet
ics)
,2003
[13,
14]
n=
131
vs.
148
sub
gro
up
of
dia
bet
ics
pati
ents
of
SIR
IUS
study
SE
Svs.
BM
Sdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:,
US
7.2. META-ANALYSIS RESULTS 95
7.2 Meta-analysis results
The results are detailed in table 7.2 (page 96). This table is followed by the Forest’s plotcorresponding to each endpoint.
Paclitaxel eluting stent versus bare-metal stent
All the 4 studies had extractable data about the number of participants with target lesionrevascularisation . The analysis detected a statistically significant difference in favor of pacli-taxel eluting stent in target lesion revascularisation , with a RR of 0.40 (95% CI 0.27 to 0.60,p=0.0000). No heterogeneity across these trials was detected (p =0.3757, I2 = 0.03%).
Data from 3 (among 4) trials evaluating angiographic restenosis were available. Theanalysis detected a statistically significant difference in favor of paclitaxel eluting stent in an-giographic restenosis , with a RR of 0.17 (95% CI 0.08 to 0.37, p=0.0000). No heterogeneityacross these trials was detected (p =0.9222, I2 = 0.00%).
Sirolimus eluting stent versus bare-metal stent
Data from 3 (among 7) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 0.83 (95%CI 0.21 to 3.34, p=0.7950) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant. No heterogeneity across these trials was detected (p=0.3992, I2 = 0.00%).
Data from 2 (among 7) trials evaluating MI (fatal and non fatal) were available. Whenpooled together, there was no statistically significant difference between the groups in MI (fataland non fatal), with a RR of 0.80 (95% CI 0.42 to 1.55, p=0.5128). No heterogeneity acrossthese trials was detected (p =0.9635, I2 = 0.00%).
Data from 3 (among 7) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of 0.46(95% CI 0.32 to 0.67, p=0.0000). No heterogeneity across these trials was detected (p =0.3847,I2 = 0.00%).
Only one of the 7 studies eligible for this comparison provided data on 2 yr MACE . Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in 2 yrMACE , with a RR of 0.31 (95% CI 0.16 to 0.59, p=0.0000).
Only one of the 7 studies eligible for this comparison provided data on target-vessel revas-cularization. The analysis detected a statistically significant difference in favor of sirolimuseluting stent in target-vessel revascularization, with a RR of 0.25 (95% CI 0.10 to 0.61, p=0.0026).
Only one of the 7 studies eligible for this comparison provided data on 2 yr TLR . Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in 2 yrTLR , with a RR of 0.22 (95% CI 0.10 to 0.50, p=0.0000).
Data from 5 (among 7) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of sirolimus eluting stentin target lesion revascularisation , with a RR of 0.24 (95% CI 0.13 to 0.44, p=0.0000). Noheterogeneity across these trials was detected (p =0.1320, I2 = 0.43%).
Only one of the 7 studies eligible for this comparison provided data on CABG. No statisti-cally significant difference between the groups was found in CABG, with a RR of 1.03 (95% CI0.02 to 51.15, p=0.9884).
Data from 4 (among 7) trials evaluating angiographic restenosis were available. Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in angio-graphic restenosis , with a RR of 0.18 (95% CI 0.11 to 0.29, p=0.0000). No heterogeneity acrossthese trials was detected (p =0.4447, I2 = 0.00%).
96 CHAPTER 7. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Table 7.2: Results details - Diabetic patients - comparison versus bare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Paclitaxel eluting stent versus bare-metal stent
target lesion revascularisation RR=0.40 [0.27;0.60] 0.0000 0.3757 (I=0.03) 4 834
angiographic restenosis RR=0.17 [0.08;0.37] 0.0000 0.9222 (I=0.00) 3 485
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.83 [0.21;3.34] 0.7950 0.3992 (I=0.00) 3 295
MI (fatal and non fatal) RR=0.80 [0.42;1.55] 0.5128 0.9635 (I=0.00) 2 212
MACE RR=0.46 [0.32;0.67] 0.0000 0.3847 (I=0.00) 3 372
2 yr MACE RR=0.31 [0.16;0.59] 0.0000 1.0000 (I=0.00) 1 158
target-vessel revascularization RR=0.25 [0.10;0.61] 0.0026 1.0000 (I=0.00) 1 138
2 yr TLR RR=0.22 [0.10;0.50] 0.0000 1.0000 (I=1.00) 1 158
target lesion revascularisation RR=0.24 [0.13;0.44] 0.0000 0.1320 (I=0.43) 5 499
CABG RR=1.03 [0.02;51.15] 0.9884 1.0000 (I=0.00) 1 138
Stent thrombosis (any, end offollow up)
RR=0.80 [0.16;4.08] 0.7916 0.9641 (I=0.00) 3 295
Acute stent thrombosis(<=24h)
RR=1.03 [0.02;51.15] 0.9884 1.0000 (I=0.00) 1 138
sub acute stent thrombosis(1-30 days)
RR=1.03 [0.09;11.21] 0.9820 0.5687 (I=0.00) 2 296
late stent thrombosis (31days -1year)
RR=0.51 [0.05;5.60] 0.5849 0.9988 (I=0.00) 2 296
angiographic restenosis RR=0.18 [0.11;0.29] 0.0000 0.4447 (I=0.00) 4 422
Figure 7.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 3/68 2/70 1.54 [0.27;8.96]
SES-SMARt (diabetics),200 0/29 1/45 0.78 [0.03;22.39]
DECODE,2005 0/54 2/29 0.13 [0.01;2.88]
Global p ass= 0.7950 0.83 [0.21;3.34]
Het. between 3 trials p=0.3992 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
7.2. META-ANALYSIS RESULTS 97
Figure 7.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 11/68 14/70 0.81 [0.40;1.65]
SES-SMARt (diabetics),200 2/29 4/45 0.78 [0.15;3.97]
Global p ass= 0.5128 0.80 [0.42;1.55]
Het. between 2 trials p=0.9635 I2=0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 7.3: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 15/68 28/70 0.55 [0.32;0.94]
SES-SMARt (diabetics),200 6/29 17/45 0.55 [0.24;1.23]
DIABETES,2005 9/80 29/80 0.31 [0.16;0.61]
Global p ass= 0.0000 0.46 [0.32;0.67]
Het. between 3 trials p=0.3847 I2=0.00
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 7.4: Forest’s plot for 2 yr MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DIABETES,2005 10/78 33/80 0.31 [0.16;0.59]
Global p ass= 0.0000 0.31 [0.16;0.59]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
98 CHAPTER 7. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 7.5: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 5/68 21/70 0.25 [0.10;0.61]
Global p ass= 0.0026 0.25 [0.10;0.61]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 7.6: Forest’s plot for 2 yr TLR
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DIABETES,2005 6/78 28/80 0.22 [0.10;0.50]
Global p ass= 0.0000 0.22 [0.10;0.50]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
7.2. META-ANALYSIS RESULTS 99
Figure 7.7: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS VI (diabetics),2005 /39 /50 0.20 [0.05;0.82]
TAXUS V (diabetics),2005 /178 /171 0.54 [0.31;0.95]
TAXUS IV (diabetics),2005 /155 /163 0.37 [0.20;0.69]
TAXUS II (diabetics),2003 /37 /41 0.16 [0.03;0.95]
Global p ass= 0.0000 0.40 [0.27;0.60]
Het. between 4 trials p=0.3757 I2=0.03
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 4/68 21/70 0.20 [0.07;0.54]
SES-SMARt (diabetics),200 5/29 14/45 0.55 [0.22;1.37]
DECODE,2005 5/54 8/29 0.34 [0.12;0.93]
DIABETES,2005 /80 /80 0.20 [0.08;0.50]
Ravel (diabetics),2004 /19 /25 0.07 [0.02;0.27]
Global p ass= 0.0000 0.24 [0.13;0.44]
Het. between 5 trials p=0.1320 I2=0.43
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 7.8: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 0/68 0/70 1.03 [0.02;51.15]
Global p ass= 0.9884 1.03 [0.02;51.15]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
100 CHAPTER 7. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 7.9: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 1/68 1/70 1.03 [0.07;16.13]
SES-SMARt (diabetics),200 1/29 2/45 0.78 [0.07;8.17]
DECODE,2005 0/54 0/29 0.54 [0.01;26.37]
Global p ass= 0.7916 0.80 [0.16;4.08]
Het. between 3 trials p=0.9641 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 7.10: Forest’s plot for acute stent thrombosis (<=24h)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 0/68 0/70 1.03 [0.02;51.15]
Global p ass= 0.9884 1.03 [0.02;51.15]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 7.11: Forest’s plot for sub acute stent thrombosis (1-30 days)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 1/68 0/70 2.06 [0.07;60.37]
DIABETES,2005 0/78 1/80 0.51 [0.02;15.07]
Global p ass= 0.9820 1.03 [0.09;11.21]
Het. between 2 trials p=0.5687 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 101
Figure 7.12: Forest’s plot for late stent thrombosis (31days - 1year)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
DESSERT,2008 0/68 1/70 0.51 [0.02;15.09]
DIABETES,2005 0/78 1/80 0.51 [0.02;15.07]
Global p ass= 0.5849 0.51 [0.05;5.60]
Het. between 2 trials p=0.9988 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 7.13: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS VI (diabetics),2005 /39 /50 0.20 [0.06;0.66]
TAXUS IV (diabetics),2005 /155 /163 0.16 [0.06;0.43]
TAXUS II (diabetics),2003 /37 /41 0.07 [0.00;34.60]
Global p ass= 0.0000 0.17 [0.08;0.37]
Het. between 3 trials p=0.9222 I2=0.00
Sirolimus eluting stent versus bare-metal stent
SCORPIUS,2007 6/68 32/76 0.21 [0.09;0.47]
SES-SMARt (diabetics),200 /29 /45 0.19 [0.06;0.60]
DIABETES,2005 6/80 29/80 0.21 [0.09;0.47]
Ravel (diabetics),2004 /19 /25 0.06 [0.02;0.24]
Global p ass= 0.0000 0.18 [0.11;0.29]
Het. between 4 trials p=0.4447 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo A, Thuesen L, Hauptman K, MarcoJ, Wijns W, Popma JJ, Koglin J, Russell ME. Clinical efficacy of polymer-based paclitaxel-eluting stents inthe treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for theuse of drug-eluting stents in contemporary clinical practice.. Circulation 2005;112:3306-13 [PMID=16286586]
102 REFERENCES
[2] Ellis SG. TAXUS V trial global results: expanding the randomizeddata. 2005 American College of Cardiol-ogyAnnual Scientific Session
[3] Hermiller JB, Raizner A, Cannon L, Gurbel PA, Kutcher MA, Wong SC, Russell ME, Ellis SG, MehranR, Stone GW. Outcomes with the polymer-based paclitaxel-eluting TAXUS stent in patients with diabetesmellitus: the TAXUS-IV trial.. J Am Coll Cardiol 2005;45:1172-9 [PMID=15837245]
[4] Hermiller J.. Diabetic results: Taxus II, IV and VI. TCT [PMID=0]
[5] Maresta A, Varani E, Balducelli M, Varbella F, Lettieri C, Uguccioni L, Sangiorgio P, Zoccai GB. Com-parison of effectiveness and safety of sirolimus-eluting stents versus bare-metal stents in patients with dia-betes mellitus (from the Italian Multicenter Randomized DESSERT Study).. Am J Cardiol 2008;101:1560-6[PMID=18489933]
[6] Baumgart D.. One year results of the SCORPIUS-Trial - a Germanmulticenter investigation on the effectiveness of sirolimus-elutingstents in diabetic patients. Annual Scientifi c Meeting of theTranscatheterCardiovascular Therapeutics. Washington, DC;Oct 2227, 2006. Abstract 288.
[7] Baumgart D, Klauss V, Baer F, Hartmann F, Drexler H, Motz W, Klues H, Hofmann S, Vlker W, Pfan-nebecker T, Stoll HP, Nickenig G. One-year results of the SCORPIUS study: a German multicenter inves-tigation on the effectiveness of sirolimus-eluting stents in diabetic patients.. J Am Coll Cardiol 2007 Oct23;50:1627-34 [PMID=17950142]
[8] Ortolani P, Ardissino D, Cavallini C, Bramucci E, Indolfi C, Aquilina M, Marzocchi A. Effect of sirolimus-eluting stent in diabetic patients with small coronary arteries (a SES-SMART substudy).. Am J Cardiol2005;96:1393-8 [PMID=16275185]
[9] Chan C, Zambahari R, Kaul U, Cohen SA, Buchbinder M.. Outcomesin diabetic patients with multivesseldisease and long lesions: resultsfrom the DECODE study. Am J Cardiol 2005; 96 (suppl 7A): 31H
[10] Sabat M, Jimnez-Quevedo P, Angiolillo DJ, Gmez-Hospital JA, Alfonso F, Hernndez-Antoln R, GoicoleaJ, Bauelos C, Escaned J, Moreno R, Fernndez C, Fernndez-Avils F, Macaya C. Randomized comparison ofsirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients:the diabetes and sirolimus-eluting stent (DIABETES) trial.. Circulation 2005;112:2175-83 [PMID=16203930]
[11] Jimnez-Quevedo P, Sabat M, Angiolillo DJ, Alfonso F, Hernndez-Antoln R, SanMartn M, Gmez-HospitalJA, Bauelos C, Escaned J, Moreno R, Fernndez C, Fernndez-Avils F, Macaya C. Long-term clinical benefitof sirolimus-eluting stent implantation in diabetic patients with de novo coronary stenoses: long-term resultsof the DIABETES trial.. Eur Heart J 2007;28:1946-52 [PMID=17562666]
[12] Abizaid A, Costa MA, Blanchard D, Albertal M, Eltchaninoff H, Guagliumi G, Geert-Jan L, Abizaid AS,Sousa AG, Wuelfert E, Wietze L, Sousa JE, Serruys PW, Morice MC. Sirolimus-eluting stents inhibitneointimal hyperplasia in diabetic patients. Insights from the RAVEL Trial.. Eur Heart J 2004;25:107-12[PMID=14720526]
[13] Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ,Williams DO, Teirstein PS, Jaeger JL, Kuntz RE. Sirolimus-eluting stents versus standard stents in patientswith stenosis in a native coronary artery.. N Engl J Med 2003;349:1315-23 [PMID=14523139]
[14] Weisz G, Moses JW, Teirstein PS, Holmes DR Jr, Raizner AE, Satler LF, Mishkel G, Wilensky RL,Wang P, Kuntz RE, Popma JJ, Leon MB. Safety of sirolimus-eluting stenting and its effect on resteno-sis in patients with unstable angina pectoris (a SIRIUS substudy).. Am J Cardiol 2007 Apr 15;99:1044-50[PMID=17437725]
103
8 Detailed results for comparison versus paclitaxel
eluting stent in diabetic patients
8.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent
A total of 6 RCTs which randomized 1188 patients were identified: all compared sirolimuseluting stent with paclitaxel eluting stent (see 8.1 page 104).
The average study size was 198 patients per arm (range 33 to 192 per arm). The first studywas published in 2005, and the last study was published in 2008.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target lesion revascularisation data was reported in 5 trials; 2 trials reported data on MI(fatal and non fatal); 2 trials reported data on All cause death; 1 trials reported data onMACE; 1 trials reported data on CABG; 1 trials reported data on angiographic restenosis ; 3trials reported data on late stent thrombosis (31days - 1year); 1 trials reported data on Stentthrombosis (any, end of follow up); and 1 trials reported data on 4y stent thrombosis (ARC).
Following table 8.1 (page 104) summarized the main characteristics of the trials including inthis systematic review of RCTS of comparison versus paclitaxel eluting stent.
104CHAPTER 8. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Table
8.1
:M
ain
study
chara
cter
isti
cs-
Dia
bet
icpat
ients
-co
mpar
ison
vers
us
pacl
itaxel
eluti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Tom
ai,
2008
[1]
n=
60
vs.
60
dia
bet
icpati
ent
wit
hm
ult
iple
de
nov
oco
ronary
art
ery
lesi
ons
siro
lim
us-
eluti
ng
sten
tvs.
pacl
itaxel
-elu
ting
sten
tN
AC
ross
over
Pri
mary
endp
oin
t:in
-ste
nt
late
lum
inal
loss
Sin
gle
cente
r,It
aly
Kim
,2008
[2]
n=
85
vs.
84
Kore
an
dia
bet
icpati
ents
wit
hhig
h-g
rade
de
nov
oco
ronary
lesi
ons
(ste
nosi
sof>
70
per
cent
of
the
lum
inal
dia
met
er)
requir
ing
<3
sten
ts
Cypher
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:la
telu
men
loss
6ce
ntr
es,
Kore
a
RE
AL
ITY
(dia
bet
ics)
,2006
[3]
n=
187
vs.
192
SE
Svs.
PE
Sop
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:,
worl
dw
ide
SIR
TA
Xdia
bet
ics,
2005
[4,
5]
n=
108
vs.
93
Sub
gro
ups
of
dia
bet
ics
pati
ents
wit
hei
ther
stable
angin
aor
an
acu
teco
ronary
syndro
me
Cypher
vs.
Taxus
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:ca
rdia
cdea
th,
AM
I,T
LR
2ce
ntr
es,
Sw
itze
rland
ISA
R-D
IAB
ET
ES,
2005
[6]
n=
125
vs.
125
Dia
bet
icpati
ents
.A
Por
posi
tive
stre
ss,
no
AM
Iw
ith
clin
ically
signifi
cant
angio
gra
phic
sten
osi
sin
anati
ve
coro
nary
ves
sel
Taxus
vs.
Cypher
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:L
ate
lum
enlo
ss2
centr
es,
Ger
many
TA
xi
(dia
bet
ics)
,0
[]n
=33
vs.
36
SE
Svs.
PE
Sop
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:,
Sw
itze
rland
8.2. META-ANALYSIS RESULTS 105
8.2 Meta-analysis results
The results are detailed in table 8.2 (page 105). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus paclitaxel eluting stent
Data from 2 (among 6) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and paclitaxeleluting stent, with a RR of 0.71 (95%CI 0.23 to 2.21, p=0.5568) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant. No heterogeneity across these trials was detected (p=0.7985, I2 = 0.00%).
Data from 2 (among 6) trials evaluating MI (fatal and non fatal) were available. Whenpooled together, there was no statistically significant difference between the groups in MI (fataland non fatal), with a RR of 1.50 (95% CI 0.43 to 5.25, p=0.5297). No heterogeneity acrossthese trials was detected (p =0.7407, I2 = 0.00%).
Only one of the 6 studies eligible for this comparison provided data on MACE. No statisti-cally significant difference between the groups was found in MACE, with a RR of 1.64 (95% CI0.29 to 9.19, p=0.5759).
Data from 5 (among 6) trials evaluating target lesion revascularisation were available.When pooled together, there was no statistically significant difference between the groups intarget lesion revascularisation , with a RR of 0.72 (95% CI 0.40 to 1.29, p=0.2697). No hetero-geneity across these trials was detected (p =0.2287, I2 = 0.29%).
Only one of the 6 studies eligible for this comparison provided data on CABG. No statisti-cally significant difference between the groups was found in CABG, with a RR of 0.99 (95% CI0.02 to 49.23, p=0.9953).
Only one of the 6 studies eligible for this comparison provided data on angiographicrestenosis . No statistically significant difference between the groups was found in angiographicrestenosis , with a RR of 0.40 (95% CI 0.08 to 1.98, p=0.2591).
Table 8.2: Results details - Diabetic patients - comparison versus paclitaxel eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.71 [0.23;2.21] 0.5568 0.7985 (I=0.00) 2 419
MI (fatal and non fatal) RR=1.50 [0.43;5.25] 0.5297 0.7407 (I=0.00) 2 419
MACE RR=1.64 [0.29;9.19] 0.5759 1.0000 (I=0.00) 1 69
target lesion revascularisation RR=0.72 [0.40;1.29] 0.2697 0.2287 (I=0.29) 5 1068
CABG RR=0.99 [0.02;49.23] 0.9953 1.0000 (I=0.00) 1 169
Stent thrombosis (any, end offollow up)
RR=0.25 [0.01;5.49] 0.3791 1.0000 (I=0.00) 1 250
4y stent thrombosis (ARC) RR=0.25 [0.01;5.49] 0.3791 1.0000 (I=0.00) 1 250
late stent thrombosis (31days -1year)
RR=0.41 [0.11;1.51] 0.1790 0.5890 (I=0.00) 3 830
angiographic restenosis RR=0.40 [0.08;1.98] 0.2591 1.0000 (I=1.00) 1 169
106CHAPTER 8. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 8.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Kim,2008 1/85 1/84 0.99 [0.06;15.54]
ISAR-DIABETES,2005 4/125 6/125 0.67 [0.19;2.31]
Global p ass= 0.5568 0.71 [0.23;2.21]
Het. between 2 trials p=0.7985 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 8.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Kim,2008 1/85 1/84 0.99 [0.06;15.54]
ISAR-DIABETES,2005 5/125 3/125 1.67 [0.41;6.82]
Global p ass= 0.5297 1.50 [0.43;5.25]
Het. between 2 trials p=0.7407 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 8.3: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
TAxi (diabetics) 3/33 2/36 1.64 [0.29;9.19]
Global p ass= 0.5759 1.64 [0.29;9.19]
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
8.2. META-ANALYSIS RESULTS 107
Figure 8.4: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Kim,2008 2/85 4/84 0.49 [0.09;2.63]
REALITY (diabetics),2006 15/187 10/192 1.54 [0.71;3.34]
SIRTAX diabetics,2005 6/108 12/93 0.43 [0.17;1.10]
ISAR-DIABETES,2005 8/125 15/125 0.53 [0.23;1.21]
TAxi (diabetics) 1/33 1/36 1.09 [0.07;16.75]
Global p ass= 0.2697 0.72 [0.40;1.29]
Het. between 5 trials p=0.2287 I2=0.29
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 8.5: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Kim,2008 0/85 0/84 0.99 [0.02;49.23]
Global p ass= 0.9953 0.99 [0.02;49.23]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 8.6: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-DIABETES,2005 0/125 2/125 0.25 [0.01;5.49]
Global p ass= 0.3791 0.25 [0.01;5.49]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
108CHAPTER 8. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 8.7: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-DIABETES,2005 0/125 2/125 0.25 [0.01;5.49]
Global p ass= 0.3791 0.25 [0.01;5.49]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 8.8: Forest’s plot for late stent thrombosis (31days - 1year)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
REALITY (diabetics),2006 2/187 6/192 0.34 [0.07;1.67]
SIRTAX diabetics,2005 0/108 2/93 0.22 [0.01;4.72]
ISAR-DIABETES,2005 1/125 0/125 2.00 [0.07;59.08]
Global p ass= 0.1790 0.41 [0.11;1.51]
Het. between 3 trials p=0.5890 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 8.9: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Kim,2008 2/85 5/84 0.40 [0.08;1.98]
Global p ass= 0.2591 0.40 [0.08;1.98]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 109
References
[1] Tomai F, Reimers B, De Luca L, Galassi AR, Gaspardone A, Ghini AS, Ferrero V, Favero L, Gioffr G, PratiF, Tamburino C, Ribichini F, . Head-to-head comparison of sirolimus- and paclitaxel-eluting stent in thesame diabetic patient with multiple coronary artery lesions: a prospective, randomized, multicenter study..Diabetes Care 2008;31:15-9. [PMID=17909090]
[2] Kim MH, Hong SJ, Cha KS, Park HS, Chae SC, Hur SH, Gwon HC, Bae JH, Lim DS. Effect of Paclitaxel-eluting versus sirolimus-eluting stents on coronary restenosis in Korean diabetic patients.. J Interv Cardiol2008 Jun;21:225-31 [PMID=18341520]
[3] Windecker S.. Cypher is preferred in diabetics. 2006 Transcatheter Cardiovascular Therapeutics AnnualMeetings
[4] Togni M, Eber S, Widmer J, Billinger M, Wenaweser P, Cook S, Vogel R, Seiler C, Eberli FR, Maier W,Corti R, Roffi M, Lscher TF, Garachemani A, Hess OM, Wandel S, Meier B, Jni P, Windecker S. Impactof vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroupanalysis of the SIRTAX trial.. J Am Coll Cardiol 2007;50:1123-31 [PMID=17868802]
[5] Windecker S, Remondino A, Eberli FR, Jni P, Rber L, Wenaweser P, Togni M, Billinger M, Tller D, SeilerC, Roffi M, Corti R, Stsch G, Maier W, Lscher T, Hess OM, Egger M, Meier B. Sirolimus-eluting andpaclitaxel-eluting stents for coronary revascularization.. N Engl J Med 2005;353:653-62 [PMID=16105989]
[6] Dibra A, Kastrati A, Mehilli J, Pache J, Schhlen H, von Beckerath N, Ulm K, Wessely R, Dirschinger J,Schmig A. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients.. N Engl JMed 2005;353:663-70 [PMID=16105990]
110CHAPTER 9. DETAILS FOR COMPARISON VERSUS RAPAMYCIN ELUTING STENT
9 Detailed results for comparison versus rapamycin
eluting stent in diabetic patients
9.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus rapamycineluting stent
Only one trial which randomized 131 patients was identified: all compared paclitaxel elutingstent with rapamycin eluting stent (see 9.1 page 111).
The average study size was 131 patients per arm (range 58 to 73 per arm). The first studywas published in 2006, and the last study was published in 2006.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
data was reported in trials;Following table 9.1 (page 111) summarized the main characteristics of the trials including in
this systematic review of RCTS of comparison versus rapamycin eluting stent.
9.1. AVAILABLE RCTS 111
Table
9.1
:M
ain
study
chara
cter
isti
cs-
Dia
bet
icpat
ients
-co
mpar
ison
vers
us
rapam
yci
nel
uti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Paclita
xelelu
ting
stentvers
us
rapam
ycin
elu
ting
stent
ISA
R-t
est
(dia
bet
ics)
,2006
[1]
n=
73
vs.
58
dia
bet
ics
pati
ents
wit
hde
nov
ole
sions
innati
ve
coro
nary
ves
sels
,ex
cludin
gth
ele
ftm
ain
trunk
Taxus
vs.
rapam
yci
nst
ent
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:,
ger
many
112 REFERENCES
9.2 Meta-analysis results
The results are detailed in table 9.2 (page 112). This table is followed by the Forest’s plotcorresponding to each endpoint.
Paclitaxel eluting stent versus rapamycin eluting stent
No data were presented in the 1 trial identified
Table 9.2: Results details - Diabetic patients - comparison versus rapamycin eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
Paclitaxel eluting stent versus rapamycin eluting stent
No data were presented in the trial identified
References
[1] Mehilli J, Kastrati A, Wessely R, Dibra A, Hausleiter J, Jaschke B, Dirschinger J, Schmig A. Randomizedtrial of a nonpolymer-based rapamycin-eluting stent versus a polymer-based paclitaxel-eluting stent for thereduction of late lumen loss.. Circulation 2006;113:273-9 [PMID=16391155]
REFERENCES 113
10 Ongoing studies of Diabetic patients
10.1 List of ongoing trials
A total of 4 studies were still ongoing at the date of this report. A list of these ongoing studieswith a brief description is given table 10.1.
Table 10.1: Ongoing studies for Diabetic patients
Study Description
PEPCAD IV (0)[] NCT00462631
Paclitaxel-eluting PTCA-balloon dilation (SeQuentTM Please) fol-lowed by cobalt-chromium stent (CoroflexTM Blue) deployment vs.Taxus Libert
patients with diabetes mellitus
DIABEDES IV (0)[] NCT00552994
Cypher select plus vs. Xience V
diabetic patients
FREEDOM (0)[] NCT00086450
TAXUS or CYPHER vs. CABG
diabetic individuals with multivessel coronary artery disease
Lipsia-Yukon-DM (0)[] NCT00368953
Yukon Choice stent system vs. Taxus Libert stent system
Patients With Diabetes Mellitus
References
114 REFERENCES
Part III
Acute myocardial infarction
115
116
117
11 Overview of available evidence for acute
myocardial infarction
A total of 10 RCTs which randomized 3337 patients were identified. (see tables 11.1 to 11.2 )In all, 8 reports concerned comparison versus bare-metal stent and 2 the comparison versus
paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 12 (page 129)
for comparison versus bare-metal stent and in section 13 (page 140 ) for comparison versuspaclitaxel eluting stent.
The average study size was 370 patients per arm (range 54 to 359 per arm). The first studywas published in 2003, and the last study was published in 2008.
All trials were open-label in design. All included studies were reported in English language.We found one unpublished trial.
118CHAPTER 11. OVERVIEW OF AVAILABLE EVIDENCE FOR ACUTE MYOCARDIAL INFARCTION
Table
11.1
:M
ain
study
chara
cter
isti
cs-
Acu
tem
yoca
rdia
lin
farc
tion
-co
mpari
son
vers
us
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Dru
gelu
ting
stentvers
us
bare
-meta
lst
ent
DE
DIC
AT
ION
,2008
[1]
DE
Scu
rren
tly
use
dw
ith
or
wit
hout
dis
tal
pro
tect
ion
vs.
BM
Sw
ith
or
wit
hout
dis
tal
pro
tect
ion
313
vs.
313
op
enP
ara
llel
gro
ups
loss
of
the
lum
endia
met
erD
enm
ark
.
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
HA
AM
U-S
TE
NT
,2006
[2]
Taxus
Expre
ssvs.
Bare
-met
al-
sten
t70
vs.
75
op
enP
ara
llel
gro
ups
none
Fin
land
PA
SSIO
N,
2006
[3]
Taxus
Expre
ss2
vs.
Expre
ss2
or
Lib
ert
310
vs.
309
op
enP
ara
llel
gro
ups
Com
bin
ati
on
of
card
iacd
eath
,A
MI,
TL
R
The
Net
her
lands
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
MIS
SIO
N,
2008
[4,
5]
Cypher
vs.
Vis
ion
158
vs.
152
single
-blind
Para
llel
gro
ups
inse
gm
ent
Late
lum
enlo
ssat
9m
o
the
Net
her
lands
Daz
de
laL
lera
,2007
[6]
siro
lim
us-
eluti
ng
sten
tsvs.
unco
ate
dst
ents
60
vs.
54
op
enP
ara
llel
gro
ups
card
iac
dea
th,
MI,
TL
RSpain
SE
SA
MI,
2007
[7]
Cypher
vs.
BX
sten
t,C
ord
is160
vs.
160
op
enP
ara
llel
gro
ups
Bin
ary
rest
enosi
sat
1y
Italy
TY
PH
OO
N,
2006
[8]
Cypher
or
Cypher
Sel
ect
vs.
any
com
mer
ciallyav
ailable
unco
ate
dst
ent
356
vs.
359
op
enP
ara
llel
gro
ups
Com
bin
ati
on
of
ves
selr
elate
d-
dea
th,
AM
I,T
VR
Worl
dw
ide
(15
countr
ies)
Pasc
eri,
2003
[9]
unpublish
edC
ypher
vs.
NA
vs.
NA
NA
Para
llel
gro
ups
NA
NA
119
Table
11.2
:M
ain
study
chara
cter
isti
cs-
Acu
tem
yoca
rdia
lin
farc
tion
-co
mpari
son
vers
us
pacl
itaxel
eluti
ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
paclita
xel
elu
ting
stent
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
PR
OSIT
,2006
[1,
2,
3]
SE
SC
ord
isvs.
PE
SB
ost
on
Sci
enti
fic
154
vs.
154
op
enP
ara
llel
gro
ups
Late
lum
enlo
ssK
ore
a
Di
Lore
nzo
etal.,
2005
[4]
siro
lim
us
vs.
pacl
itaxel
90
vs.
90
op
enP
ara
llel
gro
ups
NA
NA
120CHAPTER 11. OVERVIEW OF AVAILABLE EVIDENCE FOR ACUTE MYOCARDIAL INFARCTION
11.1 Main results for Acute myocardial infarction
The meta-analysis of the available trials provide the results listed in tables 11.3 to 11.4 (page120) and in the following graphs.
11.2 comparison versus bare-metal stent - summary of results
Drug eluting stent was superior to bare-metal stent in terms of MACE (RR=0.62, 95%CI 0.40 to 0.97, p=0.0366, 1 trial) and target-vessel revascularization (RR=0.39, 95% CI 0.22to 0.68, p=0.0000, 1 trial) .However, no significant difference was found on all cause death(RR=2.00, 95% CI 0.87 to 4.61, p=0.1034, 1 trial) and cardiac death (RR=2.60, 95% CI 0.94to 7.21, p=0.0662, 1 trial) .
No significant difference was found between paclitaxel eluting stent and bare-metalstent in terms of all cause death (RR=1.11, 95% CI 0.38 to 3.24, p=0.8550, 2 trials) , MI(fatal and non fatal) (RR=0.84, 95% CI 0.26 to 2.71, p=0.7654, 1 trial) and target lesionrevascularisation (RR=0.70, 95% CI 0.38 to 1.29, p=0.2540, 1 trial) .
Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.48,95% CI 0.33 to 0.71, p=0.0000, 2 trials) , target-vessel revascularization (RR=0.40, 95% CI 0.28to 0.58, p=0.0000, 3 trials) , target lesion revascularisation (RR=0.36, 95% CI 0.18 to 0.71,p=0.0029, 2 trials) and angiographic restenosis (RR=0.23, 95% CI 0.06 to 0.93, p=0.0396, 2trials) with a random effect model in reason of a heterogeneity (Het. p=0.0441) .However, nosignificant difference was found on all cause death (RR=0.69, 95% CI 0.34 to 1.41, p=0.3077, 3trials) , cardiac death (RR=0.96, 95% CI 0.14 to 6.74, p=0.9689, 1 trial) , MI (fatal and nonfatal) (RR=0.68, 95% CI 0.33 to 1.40, p=0.2968, 2 trials) and CABG (RR=0.38, 95% CI 0.08to 1.95, p=0.2493, 1 trial) .
11.3 comparison versus paclitaxel eluting stent - summary ofresults
No significant difference was found between sirolimus eluting stent and paclitaxel elutingstent in terms of all cause death (RR=0.80, 95% CI 0.39 to 1.63, p=0.5391, 2 trials) , cardiacdeath (RR=0.56, 95% CI 0.17 to 1.87, p=0.3472, 1 trial) , MI (fatal and non fatal) (RR=1.16,95% CI 0.39 to 3.40, p=0.7909, 2 trials) , MACE (RR=0.50, 95% CI 0.23 to 1.08, p=0.0770, 1trial) and target lesion revascularisation (RR=0.66, 95% CI 0.30 to 1.43, p=0.2916, 2 trials) .
Table 11.3: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Drug eluting stent versus bare-metal stent
All cause death RR=2.00 0.87;4.61 0.1034 1.0000 (0.00) 1 626
cardiac death RR=2.60 0.94;7.21 0.0662 1.0000 (0.00) 1 626
MACE RR=0.62 0.40;0.97 0.0366 1.0000 (1.00) 1 626
target-vessel revascularization RR=0.39 0.22;0.68 0.0000 1.0000 (0.00) 1 626
Stent thrombosis (any, end offollow up)
RR=0.88 0.32;2.38 0.7940 1.0000 (0.00) 1 626
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=1.11 0.38;3.24 0.8550 0.1008 (0.63) 2 750
continued...
11.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS121
Endpoint Effect 95% CI p ass p het k n
MI (fatal and non fatal) RR=0.84 0.26;2.71 0.7654 1.0000 (0.00) 1 605
target lesion revascularisation RR=0.70 0.38;1.29 0.2540 1.0000 (0.00) 1 605
Stent thrombosis (any, end offollow up)
RR=0.36 0.04;3.35 0.3676 1.0000 (1.00) 1 145
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.69 0.34;1.41 0.3077 0.5325 (0.00) 3 1329
cardiac death RR=0.96 0.14;6.74 0.9689 1.0000 (0.00) 1 310
MI (fatal and non fatal) RR=0.68 0.33;1.40 0.2968 0.6014 (0.00) 2 617
MACE RR=0.48 0.33;0.71 0.0000 0.5189 (0.00) 2 617
target-vessel revascularization RR=0.40 0.28;0.58 0.0000 0.9306 (0.00) 3 1329
target lesion revascularisation RR=0.36 0.18;0.71 0.0029 0.7933 (0.00) 2 617
CABG RR=0.38 0.08;1.95 0.2493 1.0000 (0.00) 1 310
Stent thrombosis (any, end offollow up)
RR=0.94 0.47;1.84 0.8462 0.7574 (0.00) 3 1329
4y stent thrombosis (ARC) RR=1.46 0.24;8.88 0.6834 0.6972 (0.00) 2 617
sub acute stent thrombosis(1-30 days)
RR=0.96 0.14;6.74 0.9689 1.0000 (0.00) 1 310
angiographic restenosis RR=0.23 0.06;0.93 0.0396 0.0441 (0.75) 2 476
Table 11.4: Summary of all results for comparison versus paclitaxel eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.80 0.39;1.63 0.5391 0.9202 (0.00) 2 485
cardiac death RR=0.56 0.17;1.87 0.3472 1.0000 (1.00) 1 305
MI (fatal and non fatal) RR=1.16 0.39;3.40 0.7909 0.7803 (0.00) 2 485
MACE RR=0.50 0.23;1.08 0.0770 1.0000 (0.00) 1 308
target lesion revascularisation RR=0.66 0.30;1.43 0.2916 0.8352 (0.00) 2 485
Stent thrombosis (any, end offollow up)
RR=0.34 0.03;3.36 0.3576 0.7668 (0.00) 2 488
4y stent thrombosis (ARC) RR=0.83 0.15;4.48 0.8278 0.7352 (0.00) 2 485
Acute stent thrombosis(<=24h)
RR=0.50 0.02;14.80 0.6884 1.0000 (0.00) 1 308
sub acute stent thrombosis(1-30 days)
RR=0.50 0.02;14.80 0.6884 1.0000 (0.00) 1 308
late stent thrombosis (31days -1year)
RR=1.00 0.02;50.08 1.0000 1.0000 (0.00) 1 308
122CHAPTER 11. OVERVIEW OF AVAILABLE EVIDENCE FOR ACUTE MYOCARDIAL INFARCTION
Figure 11.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Drug eluting stent versus bare-metalstent
2.00 [0.87;4.61] .10 1 626 1.00 0.00
Paclitaxel eluting stent versus bare-metalstent
1.11 [0.38;3.24] .86 2 750 .10 0.63
Sirolimus eluting stent versus bare-metalstent
0.69 [0.34;1.41] .31 3 1329 .53 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.80 [0.39;1.63] .54 2 485 .92 0.00
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 11.2: Forest’s plot for cardiac death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Drug eluting stent versus bare-metalstent
2.60 [0.94;7.21] .07 1 626 1.00 0.00
Sirolimus eluting stent versus bare-metalstent
0.96 [0.14;6.74] .97 1 310 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.56 [0.17;1.87] .35 1 305 1.00 1.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
11.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS123
Figure 11.3: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.84 [0.26;2.71] .77 1 605 1.00 0.00
Sirolimus eluting stent versus bare-metalstent
0.68 [0.33;1.40] .30 2 617 .60 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
1.16 [0.39;3.40] .79 2 485 .78 0.00
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 11.4: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Drug eluting stent versus bare-metalstent
0.62 [0.40;0.97] .04 1 626 1.00 1.00
Sirolimus eluting stent versus bare-metalstent
0.48 [0.33;0.71] .00 2 617 .52 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.50 [0.23;1.08] .08 1 308 1.00 0.00
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
124CHAPTER 11. OVERVIEW OF AVAILABLE EVIDENCE FOR ACUTE MYOCARDIAL INFARCTION
Figure 11.5: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Drug eluting stent versus bare-metalstent
0.39 [0.22;0.68] .00 1 626 1.00 0.00
Sirolimus eluting stent versus bare-metalstent
0.40 [0.28;0.58] .00 3 1329 .93 0.00
comparison versus paclitaxel eluting stent
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 11.6: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.70 [0.38;1.29] .25 1 605 1.00 0.00
Sirolimus eluting stent versus bare-metalstent
0.36 [0.18;0.71] .00 2 617 .79 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.66 [0.30;1.43] .29 2 485 .84 0.00
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
11.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS125
Figure 11.7: Forest’s plot for CABG
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.38 [0.08;1.95] .25 1 310 1.00 0.00
comparison versus paclitaxel eluting stent
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 11.8: Forest’s plot for stent thrombosis (any, end of follow up)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Drug eluting stent versus bare-metalstent
0.88 [0.32;2.38] .79 1 626 1.00 0.00
Paclitaxel eluting stent versus bare-metalstent
0.36 [0.04;3.35] .37 1 145 1.00 1.00
Sirolimus eluting stent versus bare-metalstent
0.94 [0.47;1.84] .85 3 1329 .76 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.34 [0.03;3.36] .36 2 488 .77 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
126CHAPTER 11. OVERVIEW OF AVAILABLE EVIDENCE FOR ACUTE MYOCARDIAL INFARCTION
Figure 11.9: Forest’s plot for 4y stent thrombosis (ARC)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
1.46 [0.24;8.88] .68 2 617 .70 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.83 [0.15;4.48] .83 2 485 .74 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 11.10: Forest’s plot for acute stent thrombosis (<=24h)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.50 [0.02;14.80] .69 1 308 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
11.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS127
Figure 11.11: Forest’s plot for sub acute stent thrombosis (1-30 days)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.96 [0.14;6.74] .97 1 310 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.50 [0.02;14.80] .69 1 308 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 11.12: Forest’s plot for late stent thrombosis (31days - 1year)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
1.00 [0.02;50.08] 1.00 1 308 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
128CHAPTER 11. OVERVIEW OF AVAILABLE EVIDENCE FOR ACUTE MYOCARDIAL INFARCTION
Figure 11.13: Forest’s plot for angiographic restenosis
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.23 [0.06;0.93] .04 2 476 .04 0.75
comparison versus paclitaxel eluting stent
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
129
12 Detailed results for comparison versus bare-metal
stent in acute myocardial infarction
12.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
A total of 8 RCTs which randomized 2849 patients were identified: 1 trial compared drugeluting stent with bare-metal stent , 2 trials compared paclitaxel eluting stent with bare-metalstent and 5 trials compared sirolimus eluting stent with bare-metal stent (see 12.1 page 130).
The average study size was 407 patients per arm (range 54 to 359 per arm). The first studywas published in 2003, and the last study was published in 2008.
All trials were open-label in design. All included studies were reported in English language.We found one unpublished trial.
All cause death data was reported in 6 trials; 4 trials reported data on target-vessel revas-cularization; 3 trials reported data on target lesion revascularisation ; 3 trials reported data onMI (fatal and non fatal); 3 trials reported data on MACE; 2 trials reported data on cardiacdeath; 2 trials reported data on angiographic restenosis ; 1 trials reported data on CABG; 5trials reported data on Stent thrombosis (any, end of follow up); 2 trials reported data on 4ystent thrombosis (ARC); and 1 trials reported data on sub acute stent thrombosis (1-30 days).
Following table 12.1 (page 130) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus bare-metal stent.
130 CHAPTER 12. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Table
12.1
:M
ain
study
chara
cter
isti
cs-
Acu
tem
yoca
rdia
lin
farc
tion
-co
mpari
son
vers
us
bare
-met
alst
ent
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Dru
gelu
ting
stentvers
us
bare
-meta
lst
ent
DE
DIC
AT
ION
,2008
[1]
n=
313
vs.
313
pati
ents
refe
rred
wit
hin
12
hours
from
sym
pto
monse
tof
an
ST
-ele
vati
on
myoca
rdia
lin
farc
tion
DE
Scu
rren
tly
use
dw
ith
or
wit
hout
dis
tal
pro
tect
ion
vs.
BM
Sw
ith
or
wit
hout
dis
tal
pro
tect
ion
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:lo
ssof
the
lum
endia
m-
eter
2ce
ntr
es,
Den
mark
.
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
HA
AM
U-S
TE
NT
,2006
[2]
n=
70
vs.
75
AM
I-
ST
EM
Ipati
ents
under
goin
gP
CI
Taxus
Expre
ssvs.
Bare
-met
al-
sten
top
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:none
1ce
ntr
es,
Fin
land
PA
SSIO
N,
2006
[3]
n=
310
vs.
309
Myoca
rdia
lIn
farc
tion
wit
hST
-Seg
men
tE
leva
tion
Taxus
Expre
ss2
vs.
Expre
ss2
or
Lib
ert
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:C
om
bin
ati
on
of
car-
dia
cdea
th,
AM
I,T
LR
2ce
ntr
es,
The
Net
her
lands
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
MIS
SIO
N,
2008
[4,
5]
n=
158
vs.
152
pri
mary
per
cuta
neo
us
coro
nary
inte
rven
tion
for
ST
-seg
men
tel
evati
on
myoca
rdia
lin
farc
tion
(<9h)
Cypher
vs.
Vis
ion
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:in
segm
ent
Late
lum
enlo
ssat
9m
osi
ngle
-cen
ter,
the
Net
her
lands
Daz
de
laL
lera
,2007
[6]
n=
60
vs.
54
pri
mary
per
cuta
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12.1. AVAILABLE RCTS 131
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132 CHAPTER 12. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
12.2 Meta-analysis results
The results are detailed in table 12.2 (page 133). This table is followed by the Forest’s plotcorresponding to each endpoint.
Drug eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between drug eluting stent and bare-metal stent, with a RR of 2.00 (95%CI 0.87 to 4.61, p=0.1034) in favour of bare-metal stent. Inother words, all cause death was slightly lower in the bare-metal stent group , but this was notstatistically significant.
The single study eligible for this comparison provided data on cardiac death. No statis-tically significant difference between the groups was found in cardiac death, with a RR of 2.60(95% CI 0.94 to 7.21, p=0.0662).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of drug eluting stent in MACE, with a RR of 0.62(95% CI 0.40 to 0.97, p=0.0366).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of drug eluting stentin target-vessel revascularization, with a RR of 0.39 (95% CI 0.22 to 0.68, p=0.0000).
Paclitaxel eluting stent versus bare-metal stent
All the 2 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxeleluting stent and bare-metal stent, with a RR of 1.11 (95%CI 0.38 to 3.24, p=0.8550) in favourof bare-metal stent. In other words, all cause death was slightly lower in the bare-metal stentgroup , but this was not statistically significant. No heterogeneity across these trials was detected(p =0.1008, I2 = 0.63%).
Only one of the 2 studies eligible for this comparison provided data on MI (fatal and nonfatal). No statistically significant difference between the groups was found in MI (fatal and nonfatal), with a RR of 0.84 (95% CI 0.26 to 2.71, p=0.7654).
Only one of the 2 studies eligible for this comparison provided data on target lesion revas-cularisation . No statistically significant difference between the groups was found in targetlesion revascularisation , with a RR of 0.70 (95% CI 0.38 to 1.29, p=0.2540).
Sirolimus eluting stent versus bare-metal stent
Data from 3 (among 5) trials evaluating all cause death were available. There was nostatistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 0.69 (95%CI 0.34 to 1.41, p=0.3077) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant. No heterogeneity across these trials was detected (p=0.5325, I2 = 0.00%).
Only one of the 5 studies eligible for this comparison provided data on cardiac death. Nostatistically significant difference between the groups was found in cardiac death, with a RR of0.96 (95% CI 0.14 to 6.74, p=0.9689).
Data from 2 (among 5) trials evaluating MI (fatal and non fatal) were available. Whenpooled together, there was no statistically significant difference between the groups in MI (fataland non fatal), with a RR of 0.68 (95% CI 0.33 to 1.40, p=0.2968). No heterogeneity acrossthese trials was detected (p =0.6014, I2 = 0.00%).
Data from 2 (among 5) trials evaluating MACE were available. The analysis detected astatistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of 0.48
12.2. META-ANALYSIS RESULTS 133
(95% CI 0.33 to 0.71, p=0.0000). No heterogeneity across these trials was detected (p =0.5189,I2 = 0.00%).
Data from 3 (among 5) trials evaluating target-vessel revascularization were available.The analysis detected a statistically significant difference in favor of sirolimus eluting stentin target-vessel revascularization, with a RR of 0.40 (95% CI 0.28 to 0.58, p=0.0000). Noheterogeneity across these trials was detected (p =0.9306, I2 = 0.00%).
Data from 2 (among 5) trials evaluating target lesion revascularisation were available.The analysis detected a statistically significant difference in favor of sirolimus eluting stentin target lesion revascularisation , with a RR of 0.36 (95% CI 0.18 to 0.71, p=0.0029). Noheterogeneity across these trials was detected (p =0.7933, I2 = 0.00%).
Only one of the 5 studies eligible for this comparison provided data on CABG. No statisti-cally significant difference between the groups was found in CABG, with a RR of 0.38 (95% CI0.08 to 1.95, p=0.2493).
Data from 2 (among 5) trials evaluating angiographic restenosis were available. Theanalysis detected a statistically significant difference in favor of sirolimus eluting stent in angio-graphic restenosis , with a RR of 0.23 (95% CI 0.06 to 0.93, p=0.0396). A random effect modelwas used because there was a substantial statistical heterogeneity detected between the studies(p =0.0441, I2 = 0.75%).
Table 12.2: Results details - Acute myocardial infarction - comparison versus bare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Drug eluting stent versus bare-metal stent
All cause death RR=2.00 [0.87;4.61] 0.1034 1.0000 (I=0.00) 1 626
cardiac death RR=2.60 [0.94;7.21] 0.0662 1.0000 (I=0.00) 1 626
MACE RR=0.62 [0.40;0.97] 0.0366 1.0000 (I=1.00) 1 626
target-vessel revascularization RR=0.39 [0.22;0.68] 0.0000 1.0000 (I=0.00) 1 626
Stent thrombosis (any, end offollow up)
RR=0.88 [0.32;2.38] 0.7940 1.0000 (I=0.00) 1 626
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=1.11 [0.38;3.24] 0.8550 0.1008 (I=0.63) 2 750
MI (fatal and non fatal) RR=0.84 [0.26;2.71] 0.7654 1.0000 (I=0.00) 1 605
target lesion revascularisation RR=0.70 [0.38;1.29] 0.2540 1.0000 (I=0.00) 1 605
Stent thrombosis (any, end offollow up)
RR=0.36 [0.04;3.35] 0.3676 1.0000 (I=1.00) 1 145
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.69 [0.34;1.41] 0.3077 0.5325 (I=0.00) 3 1329
cardiac death RR=0.96 [0.14;6.74] 0.9689 1.0000 (I=0.00) 1 310
MI (fatal and non fatal) RR=0.68 [0.33;1.40] 0.2968 0.6014 (I=0.00) 2 617
MACE RR=0.48 [0.33;0.71] 0.0000 0.5189 (I=0.00) 2 617
target-vessel revascularization RR=0.40 [0.28;0.58] 0.0000 0.9306 (I=0.00) 3 1329
target lesion revascularisation RR=0.36 [0.18;0.71] 0.0029 0.7933 (I=0.00) 2 617
CABG RR=0.38 [0.08;1.95] 0.2493 1.0000 (I=0.00) 1 310
Stent thrombosis (any, end offollow up)
RR=0.94 [0.47;1.84] 0.8462 0.7574 (I=0.00) 3 1329
4y stent thrombosis (ARC) RR=1.46 [0.24;8.88] 0.6834 0.6972 (I=0.00) 2 617
sub acute stent thrombosis(1-30 days)
RR=0.96 [0.14;6.74] 0.9689 1.0000 (I=0.00) 1 310
angiographic restenosis RR=0.23 [0.06;0.93] 0.0396 0.0441 (I=0.75) 2 476
134 CHAPTER 12. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 12.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Drug eluting stent versus bare-metal stent
DEDICATION,2008 16/313 8/313 2.00 [0.87;4.61]
Global p ass= 0.1034 2.00 [0.87;4.61]
Paclitaxel eluting stent versus bare-metal stent
HAAMU-STENT,2006 8/70 4/75 2.14 [0.67;6.80]
PASSION,2006 14/302 20/303 0.70 [0.36;1.36]
Global p ass= 0.8550 1.11 [0.38;3.24]
Het. between 2 trials p=0.1008 I2=0.63
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 2/158 4/152 0.48 [0.09;2.59]
SESAMI,2007 3/154 7/153 0.43 [0.11;1.62]
TYPHOON,2006 8/355 8/357 1.01 [0.38;2.65]
Global p ass= 0.3077 0.69 [0.34;1.41]
Het. between 3 trials p=0.5325 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 12.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Drug eluting stent versus bare-metal stent
DEDICATION,2008 13/313 5/313 2.60 [0.94;7.21]
Global p ass= 0.0662 2.60 [0.94;7.21]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 2/158 2/152 0.96 [0.14;6.74]
Global p ass= 0.9689 0.96 [0.14;6.74]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
12.2. META-ANALYSIS RESULTS 135
Figure 12.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
PASSION,2006 5/302 6/303 0.84 [0.26;2.71]
Global p ass= 0.7654 0.84 [0.26;2.71]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 9/158 14/152 0.62 [0.28;1.39]
SESAMI,2007 3/154 3/153 0.99 [0.20;4.85]
Global p ass= 0.2968 0.68 [0.33;1.40]
Het. between 2 trials p=0.6014 I2=0.00
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 12.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Drug eluting stent versus bare-metal stent
DEDICATION,2008 28/313 45/313 0.62 [0.40;0.97]
Global p ass= 0.0366 0.62 [0.40;0.97]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 22/158 40/152 0.53 [0.33;0.85]
SESAMI,2007 11/154 27/153 0.40 [0.21;0.79]
Global p ass= 0.0000 0.48 [0.33;0.71]
Het. between 2 trials p=0.5189 I2=0.00
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
136 CHAPTER 12. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 12.5: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Drug eluting stent versus bare-metal stent
DEDICATION,2008 16/313 41/313 0.39 [0.22;0.68]
Global p ass= 0.0000 0.39 [0.22;0.68]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 8/158 20/152 0.38 [0.17;0.85]
SESAMI,2007 8/154 22/153 0.36 [0.17;0.79]
TYPHOON,2006 20/355 47/357 0.43 [0.26;0.71]
Global p ass= 0.0000 0.40 [0.28;0.58]
Het. between 3 trials p=0.9306 I2=0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 12.6: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
PASSION,2006 16/302 23/303 0.70 [0.38;1.29]
Global p ass= 0.2540 0.70 [0.38;1.29]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 4/158 12/152 0.32 [0.11;0.97]
SESAMI,2007 7/154 18/153 0.39 [0.17;0.90]
Global p ass= 0.0029 0.36 [0.18;0.71]
Het. between 2 trials p=0.7933 I2=0.00
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
12.2. META-ANALYSIS RESULTS 137
Figure 12.7: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 2/158 5/152 0.38 [0.08;1.95]
Global p ass= 0.2493 0.38 [0.08;1.95]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 12.8: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Drug eluting stent versus bare-metal stent
DEDICATION,2008 7/313 8/313 0.88 [0.32;2.38]
Global p ass= 0.7940 0.88 [0.32;2.38]
Paclitaxel eluting stent versus bare-metal stent
HAAMU-STENT,2006 1/70 3/75 0.36 [0.04;3.35]
Global p ass= 0.3676 0.36 [0.04;3.35]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 2/158 3/152 0.64 [0.11;3.79]
SESAMI,2007 2/154 1/153 1.99 [0.18;21.69]
TYPHOON,2006 12/355 13/357 0.93 [0.43;2.01]
Global p ass= 0.8462 0.94 [0.47;1.84]
Het. between 3 trials p=0.7574 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
138 CHAPTER 12. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 12.9: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 1/158 1/152 0.96 [0.06;15.24]
SESAMI,2007 2/154 1/153 1.99 [0.18;21.69]
Global p ass= 0.6834 1.46 [0.24;8.88]
Het. between 2 trials p=0.6972 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 12.10: Forest’s plot for sub acute stent thrombosis (1-30 days)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 2/158 2/152 0.96 [0.14;6.74]
Global p ass= 0.9689 0.96 [0.14;6.74]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 12.11: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
MISSION,2008 3/158 28/152 0.10 [0.03;0.33]
SESAMI,2007 8/86 17/80 0.44 [0.20;0.96]
Global (random effect) p ass= 0.0396 0.23 [0.06;0.93]
fixed effect model p ass= 0.0000 0.28 [0.15;0.54]
Het. between 2 trials p=0.0441 I2=0.75
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 139
References
[1] Kelbaek H, Thuesen L, Helqvist S, Clemmensen P, Klvgaard L, Kaltoft A, Andersen B, Thuesen H, EngstrmT, Btker HE, Saunamki K, Krusell LR, Jrgensen E, Hansen HH, Christiansen EH, Ravkilde J, Kber L, KofoedKF, Terkelsen CJ, Lassen JF. Drug-eluting versus bare metal stents in patients with st-segment-elevationmyocardial infarction: eight-month follow-up in the Drug Elution and Distal Protection in Acute MyocardialInfarction (DEDICATION) trial.. Circulation 2008 Sep 9;118:1155-62 [PMID=18725489]
[2] Tierala I, Syvaenne M, Kupari M. Randomised comparison of apaclitaxel-eluting and a bare metal stentin STEMI-PCI. TheHAAMU-STENT-study. Annual Scientifi c Meeting of theTranscatheter CardiovascularTherapeutics; Washington, DC;Oct 2227, 2006. Abstract 178.
[3] Laarman GJ, Suttorp MJ, Dirksen MT, van Heerebeek L, Kiemeneij F, Slagboom T, van der Wieken LR,Tijssen JG, Rensing BJ, Patterson M. Paclitaxel-eluting versus uncoated stents in primary percutaneouscoronary intervention.. N Engl J Med 2006;355:1105-13 [PMID=16971717]
[4] van der Hoeven BL, Liem S, Jukema JW, et al.. Prospectiverandomised trial to evaluate the effi cacyand safety of drug-elutingstents versus barem-metal stents for the treatment of acutemyocardial infarction(the MISSION! intervention study). AnnualScientifi c Meeting of the American Heart Association. Chicago,IL,USA; Nov 1215, 2006.
[5] van der Hoeven BL, Liem SS, Jukema JW, Suraphakdee N, Putter H, Dijkstra J, Atsma DE, Bootsma M,Zeppenfeld K, Oemrawsingh PV, van der Wall EE, Schalij MJ. Sirolimus-eluting stents versus bare-metalstents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascularultrasound results and 12-month clinical outcome results from the MISSION! Intervention Study.. J AmColl Cardiol 2008 Feb 12;51:618-26 [PMID=18261680]
[6] Daz de la Llera LS, Ballesteros S, Nevado J, Fernndez M, Villa M, Snchez A, Retegui G, Garca D, Mart-nez A. Sirolimus-eluting stents compared with standard stents in the treatment of patients with primaryangioplasty.. Am Heart J 2007;154:164.e1-6 [PMID=17584571]
[7] Menichelli M, Parma A, Pucci E, Fiorilli R, De Felice F, Nazzaro M, Giulivi A, Alborino D, AzzellinoA, Violini R. Randomized trial of Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute MyocardialInfarction (SESAMI).. J Am Coll Cardiol 2007;49:1924-30 [PMID=17498576]
[8] Spaulding C, Henry P, Teiger E, Beatt K, Bramucci E, Carri D, Slama MS, Merkely B, Erglis A, MargheriM, Varenne O, Cebrian A, Stoll HP, Snead DB, Bode C. Sirolimus-eluting versus uncoated stents in acutemyocardial infarction.. N Engl J Med 2006;355:1093-104 [PMID=16971716]
[9] Pasceri V, Granatelli A, Pristipino C, et al.. A randomized trial of arapamycin-eluting stent in acute my-ocardial infarction: preliminaryresults. TCT 2003. Am J Cardiol 2003;92(Suppl 6A):1L.
140CHAPTER 13. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
13 Detailed results for comparison versus paclitaxel
eluting stent in acute myocardial infarction
13.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent
A total of 2 RCTs which randomized 488 patients were identified: all compared sirolimuseluting stent with paclitaxel eluting stent (see 13.1 page 141).
The average study size was 244 patients per arm (range 90 to 154 per arm). The first studywas published in 2005, and the last study was published in 2006.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target lesion revascularisation data was reported in 2 trials; 2 trials reported data on MI(fatal and non fatal); 2 trials reported data on All cause death; 1 trials reported data on MACE;1 trials reported data on cardiac death; 2 trials reported data on Stent thrombosis (any, endof follow up); 2 trials reported data on 4y stent thrombosis (ARC); 1 trials reported data onsub acute stent thrombosis (1-30 days); 1 trials reported data on late stent thrombosis (31days- 1year); and 1 trials reported data on Acute stent thrombosis (¡=24h).
Following table 13.1 (page 141) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus paclitaxel eluting stent.
13.1. AVAILABLE RCTS 141
Table
13.1
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142CHAPTER 13. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
13.2 Meta-analysis results
The results are detailed in table 13.2 (page 142). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus paclitaxel eluting stent
All the 2 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between sirolimuseluting stent and paclitaxel eluting stent, with a RR of 0.80 (95%CI 0.39 to 1.63, p=0.5391)in favour of sirolimus eluting stent. In other words, all cause death was slightly lower in thesirolimus eluting stent group , but this was not statistically significant. No heterogeneity acrossthese trials was detected (p =0.9202, I2 = 0.00%).
Only one of the 2 studies eligible for this comparison provided data on cardiac death. Nostatistically significant difference between the groups was found in cardiac death, with a RR of0.56 (95% CI 0.17 to 1.87, p=0.3472).
All the 2 studies had extractable data about the number of participants with MI (fatal andnon fatal). When pooled together, there was no statistically significant difference between thegroups in MI (fatal and non fatal), with a RR of 1.16 (95% CI 0.39 to 3.40, p=0.7909). Noheterogeneity across these trials was detected (p =0.7803, I2 = 0.00%).
Only one of the 2 studies eligible for this comparison provided data on MACE. No statisti-cally significant difference between the groups was found in MACE, with a RR of 0.50 (95% CI0.23 to 1.08, p=0.0770).
All the 2 studies had extractable data about the number of participants with target lesionrevascularisation . When pooled together, there was no statistically significant differencebetween the groups in target lesion revascularisation , with a RR of 0.66 (95% CI 0.30 to 1.43,p=0.2916). No heterogeneity across these trials was detected (p =0.8352, I2 = 0.00%).
Table 13.2: Results details - Acute myocardial infarction - comparison versus paclitaxel elutingstent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.80 [0.39;1.63] 0.5391 0.9202 (I=0.00) 2 485
cardiac death RR=0.56 [0.17;1.87] 0.3472 1.0000 (I=1.00) 1 305
MI (fatal and non fatal) RR=1.16 [0.39;3.40] 0.7909 0.7803 (I=0.00) 2 485
MACE RR=0.50 [0.23;1.08] 0.0770 1.0000 (I=0.00) 1 308
target lesion revascularisation RR=0.66 [0.30;1.43] 0.2916 0.8352 (I=0.00) 2 485
Stent thrombosis (any, end offollow up)
RR=0.34 [0.03;3.36] 0.3576 0.7668 (I=0.00) 2 488
4y stent thrombosis (ARC) RR=0.83 [0.15;4.48] 0.8278 0.7352 (I=0.00) 2 485
Acute stent thrombosis(<=24h)
RR=0.50 [0.02;14.80] 0.6884 1.0000 (I=0.00) 1 308
sub acute stent thrombosis(1-30 days)
RR=0.50 [0.02;14.80] 0.6884 1.0000 (I=0.00) 1 308
late stent thrombosis (31days -1year)
RR=1.00 [0.02;50.08] 1.0000 1.0000 (I=0.00) 1 308
13.2. META-ANALYSIS RESULTS 143
Figure 13.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 10/154 12/151 0.82 [0.36;1.83]
Di Lorenzo et al.,2005 3/90 4/90 0.75 [0.17;3.26]
Global p ass= 0.5391 0.80 [0.39;1.63]
Het. between 2 trials p=0.9202 I2=0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 13.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 4/154 7/151 0.56 [0.17;1.87]
Global p ass= 0.3472 0.56 [0.17;1.87]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 13.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 3/154 3/151 0.98 [0.20;4.78]
Di Lorenzo et al.,2005 4/90 3/90 1.33 [0.31;5.79]
Global p ass= 0.7909 1.16 [0.39;3.40]
Het. between 2 trials p=0.7803 I2=0.00
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
144CHAPTER 13. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 13.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 9/154 18/154 0.50 [0.23;1.08]
Global p ass= 0.0770 0.50 [0.23;1.08]
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 13.5: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 7/154 11/151 0.62 [0.25;1.57]
Di Lorenzo et al.,2005 3/90 4/90 0.75 [0.17;3.26]
Global p ass= 0.2916 0.66 [0.30;1.43]
Het. between 2 trials p=0.8352 I2=0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 13.6: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 0/154 2/154 0.25 [0.01;5.50]
Di Lorenzo et al.,2005 0/90 1/90 0.50 [0.02;14.72]
Global p ass= 0.3576 0.34 [0.03;3.36]
Het. between 2 trials p=0.7668 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
13.2. META-ANALYSIS RESULTS 145
Figure 13.7: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 2/154 2/151 0.98 [0.14;6.87]
Di Lorenzo et al.,2005 0/90 1/90 0.50 [0.02;14.72]
Global p ass= 0.8278 0.83 [0.15;4.48]
Het. between 2 trials p=0.7352 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 13.8: Forest’s plot for acute stent thrombosis (<=24h)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 0/154 1/154 0.50 [0.02;14.80]
Global p ass= 0.6884 0.50 [0.02;14.80]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 13.9: Forest’s plot for sub acute stent thrombosis (1-30 days)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 0/154 1/154 0.50 [0.02;14.80]
Global p ass= 0.6884 0.50 [0.02;14.80]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
146 REFERENCES
Figure 13.10: Forest’s plot for late stent thrombosis (31days - 1year)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
PROSIT,2006 0/154 0/154 1.00 [0.02;50.08]
Global p ass= 1.0000 1.00 [0.02;50.08]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Lee JH, Kim HS, Lee SW, et al.. Prospective randomized trial of asirolimus eluting versus a paclitaxeleluting stent for the treatmentof acute ST-elevation myocardial infarction. Annual Scientifi cMeeting of theAmerican College of Cardiology; Atlanta, GA, USA;March 1114, 2006.
[2] Kornowski R. Drug-eluting stents in ST elevation myocardial infarction: In light of the PROSIT trial..Catheter Cardiovasc Interv 2008 Jul 1;72:33-5 [PMID=18561153]
[3] Lee JH, Kim HS, Lee SW, Park JH, Choi SW, Jeong JO, Cho Y, Lee N, Rhee KS, Ko JK, SeongIW. Prospective randomized comparison of sirolimus- versus paclitaxel-eluting stents for the treatmentof acute ST-elevation myocardial infarction: pROSIT trial.. Catheter Cardiovasc Interv 2008 Jul 1;72:25-32[PMID=18412270]
[4] Di Lorenzo E, Varricchio A, Lanzillo T, et al.. Paclitaxel and sirolimusstent implantation in patients withacute myocardial infarction (abstr). Circulation 2005;112:U538
REFERENCES 147
14 Ongoing studies of Acute myocardial infarction
14.1 List of ongoing trials
Only one study was still ongoing at the date of this report. A list of these ongoing studies witha brief description is given table 14.1.
Table 14.1: Ongoing studies for Acute myocardial infarction
Study Description
ZEST AMI (0)[] NCT00422565
Endeavor (ABT 578-eluting balloon expandable stent, Medtronic) vs.Cypher or Taxus Libert
Acute Myocardial Infarction Patients
References
148 REFERENCES
Part IV
Small vessels
149
150
151
15 Overview of available evidence for small vessels
A total of 3 RCTs which randomized 1112 patients were identified. (see tables 15.1 to 15.2 )In all, 1 report concerned comparison versus bare-metal stent and 2 the comparison versus
paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 16 (page 160)
for comparison versus bare-metal stent and in section 17 (page 166 ) for comparison versuspaclitaxel eluting stent.
The average study size was 370 patients per arm (range 128 to 249 per arm). The first studywas published in 2004, and the last study was published in 2006.
Erreur ??? 0 et 0.All included studies were reported in English language. We did not found any unpublished
trial.
152 CHAPTER 15. OVERVIEW OF AVAILABLE EVIDENCE FOR SMALL VESSELS
Table
15.1
:M
ain
study
char
acte
rist
ics
-sm
allve
ssel
s-
com
par
ison
ver
sus
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
SE
S-S
MA
RT
,2004
[1]
Cypher
vs.
Bx
Sonic
129
vs.
128
single
-blind
Para
llel
gro
ups
Bin
ary
rest
enosi
sIt
alian
153
Table
15.2
:M
ain
study
char
acte
rist
ics
-sm
allve
ssel
s-
com
par
ison
ver
sus
pacl
itaxel
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ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
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gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
paclita
xel
elu
ting
stent
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
ISA
R-S
MA
RT
3,
2006
[1]
Taxus
vs.
Cypher
180
vs.
180
NA
Para
llel
gro
ups
Late
lum
enlo
ssG
erm
any
SIR
TA
X(s
mall
ves
sels
subgro
up),
2005
[2]
Cypher
vs.
Taxus
249
vs.
246
single
-blind
Para
llel
gro
ups
card
iac
dea
th,
AM
I,T
LR
Sw
itze
rland
154 CHAPTER 15. OVERVIEW OF AVAILABLE EVIDENCE FOR SMALL VESSELS
15.1 Main results for small vessels
The meta-analysis of the available trials provide the results listed in tables 15.3 to 15.4 (page154) and in the following graphs.
15.2 comparison versus bare-metal stent - summary of results
Sirolimus eluting stent was superior to bare-metal stent in terms of MI (fatal and non fatal)(RR=0.20, 95% CI 0.04 to 0.89, p=0.0344, 1 trial) , MACE (RR=0.30, 95% CI 0.16 to 0.54,p=0.0000, 1 trial) , target lesion revascularisation (RR=0.33, 95% CI 0.16 to 0.68, p=0.0024, 1trial) and angiographic restenosis (RR=0.18, 95% CI 0.10 to 0.32, p=0.0000, 1 trial) .However,no significant difference was found on all cause death (RR=0.25, 95% CI 0.01 to 5.45, p=0.3765,1 trial) and CABG (RR=0.25, 95% CI 0.01 to 5.45, p=0.3765, 1 trial) .
15.3 comparison versus paclitaxel eluting stent - summary ofresults
Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of MACE (RR=0.49,95% CI 0.29 to 0.81, p=0.0052, 1 trial) , target-vessel revascularization (RR=0.40, 95% CI0.22 to 0.71, p=0.0019, 1 trial) and target lesion revascularisation (RR=0.47, 95% CI 0.27to 0.82, p=0.0084, 2 trials) .However, no significant difference was found on all cause death(RR=0.92, 95% CI 0.52 to 1.64, p=0.7840, 2 trials) , cardiac death (RR=0.64, 95% CI 0.21 to1.92, p=0.4238, 1 trial) , MI (fatal and non fatal) (RR=1.23, 95% CI 0.61 to 2.46, p=0.5662, 2trials) and CABG (RR=0.20, 95% CI 0.02 to 1.73, p=0.1454, 1 trial) .
Table 15.3: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.25 0.01;5.45 0.3765 1.0000 (0.00) 1 257
MI (fatal and non fatal) RR=0.20 0.04;0.89 0.0344 1.0000 (0.00) 1 257
MACE RR=0.30 0.16;0.54 0.0000 1.0000 (0.00) 1 257
target lesion revascularisation RR=0.33 0.16;0.68 0.0024 1.0000 (0.00) 1 257
CABG RR=0.25 0.01;5.45 0.3765 1.0000 (0.00) 1 257
Stent thrombosis (any, end offollow up)
RR=0.25 0.03;2.19 0.2096 1.0000 (0.00) 1 257
angiographic restenosis RR=0.18 0.10;0.32 0.0000 1.0000 (0.00) 1 236
Table 15.4: Summary of all results for comparison versus paclitaxel eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.92 0.52;1.64 0.7840 0.5190 (0.00) 2 730
cardiac death RR=0.64 0.21;1.92 0.4238 1.0000 (0.00) 1 370
MI (fatal and non fatal) RR=1.23 0.61;2.46 0.5662 0.6378 (0.00) 2 730
MACE RR=0.49 0.29;0.81 0.0052 1.0000 (0.00) 1 370
target-vessel revascularization RR=0.40 0.22;0.71 0.0019 1.0000 (0.00) 1 370
target lesion revascularisation RR=0.47 0.27;0.82 0.0084 0.1739 (0.46) 2 730
continued...
15.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS155
Endpoint Effect 95% CI p ass p het k n
CABG RR=0.20 0.02;1.73 0.1454 1.0000 (0.00) 1 370
Stent thrombosis (any, end offollow up)
RR=0.85 0.26;2.75 0.7832 0.8971 (0.00) 2 730
4y stent thrombosis (ARC) RR=1.00 0.06;15.87 1.0000 1.0000 (0.00) 1 360
Figure 15.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.25 [0.01;5.45] .38 1 257 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.92 [0.52;1.64] .78 2 730 .52 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 15.2: Forest’s plot for cardiac death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.64 [0.21;1.92] .42 1 370 1.00 0.00
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
156 CHAPTER 15. OVERVIEW OF AVAILABLE EVIDENCE FOR SMALL VESSELS
Figure 15.3: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.20 [0.04;0.89] .03 1 257 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
1.23 [0.61;2.46] .57 2 730 .64 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 15.4: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.30 [0.16;0.54] .00 1 257 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.49 [0.29;0.81] .01 1 370 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
15.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS157
Figure 15.5: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.40 [0.22;0.71] .00 1 370 1.00 0.00
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 15.6: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.33 [0.16;0.68] .00 1 257 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.47 [0.27;0.82] .01 2 730 .17 0.46
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
158 CHAPTER 15. OVERVIEW OF AVAILABLE EVIDENCE FOR SMALL VESSELS
Figure 15.7: Forest’s plot for CABG
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.25 [0.01;5.45] .38 1 257 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.20 [0.02;1.73] .15 1 370 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 15.8: Forest’s plot for stent thrombosis (any, end of follow up)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.25 [0.03;2.19] .21 1 257 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.85 [0.26;2.75] .78 2 730 .90 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
15.3. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS159
Figure 15.9: Forest’s plot for 4y stent thrombosis (ARC)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
1.00 [0.06;15.87] 1.00 1 360 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 15.10: Forest’s plot for angiographic restenosis
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.18 [0.10;0.32] .00 1 236 1.00 0.00
comparison versus paclitaxel eluting stent
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
160 CHAPTER 16. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
16 Detailed results for comparison versus bare-metal
stent in small vessels
16.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
Only one trial which randomized 257 patients was identified: all compared sirolimus elutingstent with bare-metal stent (see 16.1 page 161).
The average study size was 257 patients per arm (range 128 to 129 per arm). The first studywas published in 2004, and the last study was published in 2004.
Erreur ??? 0 et 0.All included studies were reported in English language. We did not found any unpublished
trial.Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI
(fatal and non fatal); 1 trials reported data on MACE; 1 trials reported data on CABG; 1 trialsreported data on angiographic restenosis ; 1 trials reported data on All cause death; and 1 trialsreported data on Stent thrombosis (any, end of follow up).
Following table 16.1 (page 161) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus bare-metal stent.
16.1. AVAILABLE RCTS 161
Table
16.1
:M
ain
study
char
acte
rist
ics
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allve
ssel
s-
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ison
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bare
-met
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ent
Tri
al
Pati
ents
Tre
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ents
Desi
gn
Sirolim
us
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ting
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ent
SE
S-S
MA
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,2004
[1]
n=
129
vs.
128
Sta
ble
AP
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nt
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ypher
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-blind
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ups
Pri
mary
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oin
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inary
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es,
Italian
162 CHAPTER 16. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
16.2 Meta-analysis results
The results are detailed in table 16.2 (page 162). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 0.25 (95%CI 0.01 to 5.45, p=0.3765) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).The analysis detected a statistically significant difference in favor of sirolimus eluting stent inMI (fatal and non fatal), with a RR of 0.20 (95% CI 0.04 to 0.89, p=0.0344).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of0.30 (95% CI 0.16 to 0.54, p=0.0000).
The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target lesion revascularisation , with a RR of 0.33 (95% CI 0.16 to 0.68, p=0.0024).
The single study eligible for this comparison provided data on CABG. No statisticallysignificant difference between the groups was found in CABG, with a RR of 0.25 (95% CI 0.01to 5.45, p=0.3765).
The single study eligible for this comparison provided data on angiographic restenosis .The analysis detected a statistically significant difference in favor of sirolimus eluting stent inangiographic restenosis , with a RR of 0.18 (95% CI 0.10 to 0.32, p=0.0000).
Table 16.2: Results details - small vessels - comparison versus bare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.25 [0.01;5.45] 0.3765 1.0000 (I=0.00) 1 257
MI (fatal and non fatal) RR=0.20 [0.04;0.89] 0.0344 1.0000 (I=0.00) 1 257
MACE RR=0.30 [0.16;0.54] 0.0000 1.0000 (I=0.00) 1 257
target lesion revascularisation RR=0.33 [0.16;0.68] 0.0024 1.0000 (I=0.00) 1 257
CABG RR=0.25 [0.01;5.45] 0.3765 1.0000 (I=0.00) 1 257
Stent thrombosis (any, end offollow up)
RR=0.25 [0.03;2.19] 0.2096 1.0000 (I=0.00) 1 257
angiographic restenosis RR=0.18 [0.10;0.32] 0.0000 1.0000 (I=0.00) 1 236
16.2. META-ANALYSIS RESULTS 163
Figure 16.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
SES-SMART,2004 0/129 2/128 0.25 [0.01;5.45]
Global p ass= 0.3765 0.25 [0.01;5.45]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 16.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
SES-SMART,2004 2/129 10/128 0.20 [0.04;0.89]
Global p ass= 0.0344 0.20 [0.04;0.89]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 16.3: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
SES-SMART,2004 12/129 40/128 0.30 [0.16;0.54]
Global p ass= 0.0000 0.30 [0.16;0.54]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
164 CHAPTER 16. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 16.4: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
SES-SMART,2004 9/129 27/128 0.33 [0.16;0.68]
Global p ass= 0.0024 0.33 [0.16;0.68]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 16.5: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
SES-SMART,2004 0/129 2/128 0.25 [0.01;5.45]
Global p ass= 0.3765 0.25 [0.01;5.45]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 16.6: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
SES-SMART,2004 1/129 4/128 0.25 [0.03;2.19]
Global p ass= 0.2096 0.25 [0.03;2.19]
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 165
Figure 16.7: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
SES-SMART,2004 12/123 60/113 0.18 [0.10;0.32]
Global p ass= 0.0000 0.18 [0.10;0.32]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Ardissino D, Cavallini C, Bramucci E, Indolfi C, Marzocchi A, Manari A, Angeloni G, Carosio G, BonizzoniE, Colusso S, Repetto M, Merlini PA. Sirolimus-eluting vs uncoated stents for prevention of restenosis insmall coronary arteries: a randomized trial.. JAMA 2004;292:2727-34 [PMID=15585732]
166CHAPTER 17. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
17 Detailed results for comparison versus paclitaxel
eluting stent in small vessels
17.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent
A total of 2 RCTs which randomized 855 patients were identified: all compared sirolimuseluting stent with paclitaxel eluting stent (see 17.1 page 167).
The average study size was 427 patients per arm (range 180 to 249 per arm). The first studywas published in 2005, and the last study was published in 2006.
Erreur ??? 0 et 0.All included studies were reported in English language. We did not found any unpublished
trial.Target lesion revascularisation data was reported in 2 trials; 2 trials reported data on MI
(fatal and non fatal); 2 trials reported data on All cause death; 1 trials reported data on target-vessel revascularization; 1 trials reported data on MACE; 1 trials reported data on cardiac death;1 trials reported data on CABG; 2 trials reported data on Stent thrombosis (any, end of followup); and 1 trials reported data on 4y stent thrombosis (ARC).
Following table 17.1 (page 167) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus paclitaxel eluting stent.
17.1. AVAILABLE RCTS 167
Table
17.1
:M
ain
study
char
acte
rist
ics
-sm
allve
ssel
s-
com
par
ison
ver
sus
pacl
itaxel
eluti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
ISA
R-S
MA
RT
3,
2006
[1]
n=
180
vs.
180
Sm
all
ves
sels
,de
nov
ole
sions
innati
ve
coro
nary
ves
sels
wit
ha
dia
met
erof<
2.8
0m
mnondia
bet
icpati
ents
.A
Por
posi
tive
stre
ss,
no
AM
I
Taxus
vs.
Cypher
NA
Para
llel
gro
ups
Pri
mary
endp
oin
t:L
ate
lum
enlo
ss2
centr
es,
Ger
many
SIR
TA
X(s
mall
ves
sels
subgro
up),
2005
[2]
n=
249
vs.
246
Unse
lect
edpati
ents
.Sta
ble
AP
,A
CS,
incl
udin
gA
MI.
at
least
one
lesi
on
wit
hst
enosi
sof
at
least
50
per
cent
ina
ves
sel
wit
ha
refe
rence
dia
met
erb
etw
een
2.2
5and
4.0
0m
mth
at
was
suit
able
for
sten
tim
pla
nta
tion
Cypher
vs.
Taxus
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:ca
rdia
cdea
th,
AM
I,T
LR
2ce
ntr
es,
Sw
itze
rland
168CHAPTER 17. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
17.2 Meta-analysis results
The results are detailed in table 17.2 (page 168). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus paclitaxel eluting stent
All the 2 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between sirolimuseluting stent and paclitaxel eluting stent, with a RR of 0.92 (95%CI 0.52 to 1.64, p=0.7840)in favour of sirolimus eluting stent. In other words, all cause death was slightly lower in thesirolimus eluting stent group , but this was not statistically significant. No heterogeneity acrossthese trials was detected (p =0.5190, I2 = 0.00%).
Only one of the 2 studies eligible for this comparison provided data on cardiac death. Nostatistically significant difference between the groups was found in cardiac death, with a RR of0.64 (95% CI 0.21 to 1.92, p=0.4238).
All the 2 studies had extractable data about the number of participants with MI (fatal andnon fatal). When pooled together, there was no statistically significant difference between thegroups in MI (fatal and non fatal), with a RR of 1.23 (95% CI 0.61 to 2.46, p=0.5662). Noheterogeneity across these trials was detected (p =0.6378, I2 = 0.00%).
Only one of the 2 studies eligible for this comparison provided data on MACE. The analysisdetected a statistically significant difference in favor of sirolimus eluting stent in MACE, with aRR of 0.49 (95% CI 0.29 to 0.81, p=0.0052).
Only one of the 2 studies eligible for this comparison provided data on target-vessel revas-cularization. The analysis detected a statistically significant difference in favor of sirolimuseluting stent in target-vessel revascularization, with a RR of 0.40 (95% CI 0.22 to 0.71, p=0.0019).
All the 2 studies had extractable data about the number of participants with target le-sion revascularisation . The analysis detected a statistically significant difference in favor ofsirolimus eluting stent in target lesion revascularisation , with a RR of 0.47 (95% CI 0.27 to0.82, p=0.0084). No heterogeneity across these trials was detected (p =0.1739, I2 = 0.46%).
Only one of the 2 studies eligible for this comparison provided data on CABG. No statisti-cally significant difference between the groups was found in CABG, with a RR of 0.20 (95% CI0.02 to 1.73, p=0.1454).
Table 17.2: Results details - small vessels - comparison versus paclitaxel eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.92 [0.52;1.64] 0.7840 0.5190 (I=0.00) 2 730
cardiac death RR=0.64 [0.21;1.92] 0.4238 1.0000 (I=0.00) 1 370
MI (fatal and non fatal) RR=1.23 [0.61;2.46] 0.5662 0.6378 (I=0.00) 2 730
MACE RR=0.49 [0.29;0.81] 0.0052 1.0000 (I=0.00) 1 370
target-vessel revascularization RR=0.40 [0.22;0.71] 0.0019 1.0000 (I=0.00) 1 370
target lesion revascularisation RR=0.47 [0.27;0.82] 0.0084 0.1739 (I=0.46) 2 730
CABG RR=0.20 [0.02;1.73] 0.1454 1.0000 (I=0.00) 1 370
Stent thrombosis (any, end offollow up)
RR=0.85 [0.26;2.75] 0.7832 0.8971 (I=0.00) 2 730
4y stent thrombosis (ARC) RR=1.00 [0.06;15.87] 1.0000 1.0000 (I=0.00) 1 360
17.2. META-ANALYSIS RESULTS 169
Figure 17.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-SMART 3,2006 10/180 13/180 0.77 [0.35;1.71]
SIRTAX (small vessels sub 11/183 10/187 1.12 [0.49;2.58]
Global p ass= 0.7840 0.92 [0.52;1.64]
Het. between 2 trials p=0.5190 I2=0.00
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 17.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
SIRTAX (small vessels sub 5/183 8/187 0.64 [0.21;1.92]
Global p ass= 0.4238 0.64 [0.21;1.92]
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 17.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-SMART 3,2006 10/180 7/180 1.43 [0.56;3.67]
SIRTAX (small vessels sub 7/183 7/187 1.02 [0.37;2.86]
Global p ass= 0.5662 1.23 [0.61;2.46]
Het. between 2 trials p=0.6378 I2=0.00
1.00.2 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
170CHAPTER 17. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 17.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
SIRTAX (small vessels sub 19/183 40/187 0.49 [0.29;0.81]
Global p ass= 0.0052 0.49 [0.29;0.81]
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 17.5: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
SIRTAX (small vessels sub 14/183 36/187 0.40 [0.22;0.71]
Global p ass= 0.0019 0.40 [0.22;0.71]
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 17.6: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-SMART 3,2006 20/180 33/180 0.61 [0.36;1.01]
SIRTAX (small vessels sub 11/183 33/187 0.34 [0.18;0.65]
Global p ass= 0.0084 0.47 [0.27;0.82]
Het. between 2 trials p=0.1739 I2=0.46
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
17.2. META-ANALYSIS RESULTS 171
Figure 17.7: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
SIRTAX (small vessels sub 1/183 5/187 0.20 [0.02;1.73]
Global p ass= 0.1454 0.20 [0.02;1.73]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 17.8: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-SMART 3,2006 1/180 1/180 1.00 [0.06;15.87]
SIRTAX (small vessels sub 4/183 5/187 0.82 [0.22;3.00]
Global p ass= 0.7832 0.85 [0.26;2.75]
Het. between 2 trials p=0.8971 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 17.9: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-SMART 3,2006 1/180 1/180 1.00 [0.06;15.87]
Global p ass= 1.0000 1.00 [0.06;15.87]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
172 REFERENCES
References
[1] Mehilli J, Dibra A, Kastrati A, Pache J, Dirschinger J, Schmig A. Randomized trial of paclitaxel- andsirolimus-eluting stents in small coronary vessels.. Eur Heart J 2006;27:260-6 [PMID=16401670]
[2] Togni M, Eber S, Widmer J, Billinger M, Wenaweser P, Cook S, Vogel R, Seiler C, Eberli FR, Maier W,Corti R, Roffi M, Lscher TF, Garachemani A, Hess OM, Wandel S, Meier B, Jni P, Windecker S. Impactof vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroupanalysis of the SIRTAX trial.. J Am Coll Cardiol 2007;50:1123-31 [PMID=17868802]
REFERENCES 173
18 Ongoing studies of small vessels
18.1 List of ongoing trials
No ongoing trial was identified. still ongoing at the date of this report. A list of these ongoingstudies with a brief description is given table 18.1.
Table 18.1: Ongoing studies for small vessels
Study Description
References
174 REFERENCES
Part V
Long or complex lesion
175
176
177
19 Overview of available evidence for long or
complex lesion
A total of 9 RCTs which randomized 5239 patients were identified. (see tables 19.1 to 19.3 )In all, 3 reports concerned comparison versus bare-metal stent , 1 the comparison versus
CABG and 5 the comparison versus paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 20 (page 189)
for comparison versus bare-metal stent, in section 21 (page 197 ) for comparison versus CABGand in section 22 (page 202 ) for comparison versus paclitaxel eluting stent.
The average study size was 582 patients per arm (range 33 to 903 per arm). The first studywas published in 2005, and the last study was published in 2008. 2 trials were double blind and5 were open-label in design. All included studies were reported in English language. We did notfound any unpublished trial.
178CHAPTER 19. OVERVIEW OF AVAILABLE EVIDENCE FOR LONG OR COMPLEX LESION
Table
19.1
:M
ain
study
char
act
eris
tics
-lo
ng
orco
mple
xle
sion
-co
mpar
ison
ver
sus
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
TA
XU
SV
I,2005
[1,
2]
TA
XU
Svs.
Expre
ss2
sten
t219
vs.
227
double
-blind
Para
llel
gro
ups
TV
RE
uro
pe
TA
XU
SV
(all
pati
ents
),2005
[3]
TA
XU
Svs.
bare
met
al
EX
PR
ESS-2
577
vs.
579
double
-blind
Para
llel
gro
ups
TV
RU
nit
edSta
tes
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
SC
AN
DST
EN
T,
2006
[4,
5]
Cypher
vs.
Sonic
163
vs.
159
op
enP
ara
llel
gro
ups
Min
imal
lum
endia
met
erD
enm
ark
179
Table
19.2
:M
ain
study
char
acte
rist
ics
-lo
ng
orco
mple
xle
sion
-co
mpar
ison
vers
us
CA
BG
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
CA
BG
Paclita
xelelu
ting
stentvers
us
CA
BG
SY
NT
AX
,0
[]unpublish
edpacl
itaxel
(taxus
Expre
ssSR
)vs.
Coro
nary
Art
ery
Bypass
Surg
ery
903
vs.
897
op
enP
ara
llel
gro
ups
MA
CE
NA
180CHAPTER 19. OVERVIEW OF AVAILABLE EVIDENCE FOR LONG OR COMPLEX LESION
Table
19.3
:M
ain
study
char
act
eris
tics
-lo
ng
orco
mple
xle
sion
-co
mpar
ison
ver
sus
pacl
itaxel
eluti
ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
paclita
xel
elu
ting
stent
Genous
stentvers
us
paclita
xelelu
ting
stent
TR
IAS-H
R,
2008
[]G
enous
sten
t(a
nti
body-c
oate
dbare
-met
al
sten
t)fo
llow
edby
one
month
of
dual
anti
pla
tele
tth
erapy
vs.
Taxus
or
Cypher
follow
edby
at
least
six
month
sof
dual
anti
pla
tele
tth
erapy
98
vs.
95
single
-blind
Para
llel
gro
ups
targ
etle
sion
failure
NA
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Pet
ronio
etal,
2007
[1]
Cypher
vs.
Taxus
50
vs.
50
op
enP
ara
llel
gro
ups
Neo
inti
mal
hyp
erpla
sia
Italy
Cer
vin
ka,
2006
[2]
siro
lim
us-
eluti
ng
sten
tvs.
pacl
itaxel
-elu
ting
sten
t
37
vs.
33
op
enP
ara
llel
gro
ups
Neo
inti
mal
hyp
erpla
sia
NA
LO
NG
DE
SII
,2006
[3]
SE
Svs.
PE
S250
vs.
250
single
-blind
Para
llel
gro
ups
Bin
ary
rest
enosi
sK
ore
a
CO
RP
AL
,2005
[4]
siro
lim
us
vs.
pacl
itaxel
331
vs.
321
op
enP
ara
llel
gro
ups
Bin
ary
rest
enosi
sSpain
19.1. MAIN RESULTS FOR LONG OR COMPLEX LESION 181
19.1 Main results for long or complex lesion
The meta-analysis of the available trials provide the results listed in tables 19.4 to 19.6 (page181) and in the following graphs.
19.2 comparison versus bare-metal stent - summary of results
Paclitaxel eluting stent was superior to bare-metal stent in terms of MACE (RR=0.71,95% CI 0.58 to 0.88, p=0.0016, 2 trials) , target-vessel revascularization (RR=0.70, 95% CI0.53 to 0.93, p=0.0145, 1 trial) , target lesion revascularisation (RR=0.55, 95% CI 0.39 to 0.77,p=0.0000, 1 trial) and angiographic restenosis (RR=0.43, 95% CI 0.33 to 0.56, p=0.0000, 1 trial).However, no significant difference was found on all cause death (RR=0.79, 95% CI 0.30 to 2.07,p=0.6308, 2 trials) and MI (fatal and non fatal) (RR=1.16, 95% CI 0.71 to 1.88, p=0.5584, 2trials) .
Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.10,95% CI 0.04 to 0.25, p=0.0000, 1 trial) , target lesion revascularisation (RR=0.08, 95% CI0.03 to 0.23, p=0.0000, 1 trial) and angiographic restenosis (RR=0.06, 95% CI 0.02 to 0.18,p=0.0000, 1 trial) .However, no significant difference was found on all cause death (RR=0.97,95% CI 0.06 to 15.36, p=0.9823, 1 trial) .
19.3 comparison versus CABG - summary of results
Paclitaxel eluting stent was inferior to CABG in terms of MACE (RR=1.47, 95% CI 1.17to 1.84, p=0.0000, 1 trial) and target lesion revascularisation (RR=2.32, 95% CI 1.71 to 3.16,p=0.0000, 1 trial) . No significant difference was found on all cause death (RR=1.25, 95% CI0.79 to 1.98, p=0.3448, 1 trial) and MI (fatal and non fatal) (RR=1.47, 95% CI 0.93 to 2.34,p=0.1003, 1 trial) .
19.4 comparison versus paclitaxel eluting stent - summary ofresults
No significant difference was found between Genous stent and paclitaxel eluting stent interms of MI (fatal and non fatal) (RR=0.19, 95% CI 0.02 to 1.63, p=0.1309, 1 trial) and targetlesion revascularisation (RR=1.33, 95% CI 0.56 to 3.17, p=0.5154, 1 trial) .
Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of target-vesselrevascularization (RR=0.42, 95% CI 0.19 to 0.94, p=0.0357, 1 trial) , target lesion revascularisa-tion (RR=0.62, 95% CI 0.42 to 0.93, p=0.0213, 4 trials) and angiographic restenosis (RR=0.25,95% CI 0.10 to 0.60, p=0.0020, 1 trial) .However, no significant difference was found on all causedeath (RR=0.83, 95% CI 0.47 to 1.47, p=0.5323, 4 trials) , cardiac death (RR=2.00, 95% CI0.07 to 59.35, p=0.6886, 1 trial) and MI (fatal and non fatal) (RR=0.80, 95% CI 0.54 to 1.20,p=0.2848, 4 trials) .
Table 19.4: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=0.79 0.30;2.07 0.6308 0.4575 (0.00) 2 1602
continued...
182CHAPTER 19. OVERVIEW OF AVAILABLE EVIDENCE FOR LONG OR COMPLEX LESION
Endpoint Effect 95% CI p ass p het k n
MI (fatal and non fatal) RR=1.16 0.71;1.88 0.5584 0.8870 (0.00) 2 1602
MACE RR=0.71 0.58;0.88 0.0016 0.8622 (0.00) 2 1602
target-vessel revascularization RR=0.70 0.53;0.93 0.0145 1.0000 (0.00) 1 1156
target lesion revascularisation RR=0.55 0.39;0.77 0.0000 1.0000 (0.00) 1 1156
Stent thrombosis (any, end offollow up)
RR=0.75 0.23;2.45 0.6369 0.4273 (0.00) 2 1602
Acute stent thrombosis(<=24h)
RR=3.01 0.31;29.04 0.3407 1.0000 (0.00) 1 1156
sub acute stent thrombosis(1-30 days)
RR=0.34 0.04;3.04 0.3347 1.0000 (0.00) 1 1156
angiographic restenosis RR=0.43 0.33;0.56 0.0000 1.0000 (1.00) 1 1156
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.97 0.06;15.36 0.9823 1.0000 (0.00) 1 319
MACE RR=0.10 0.04;0.25 0.0000 1.0000 (0.00) 1 322
target lesion revascularisation RR=0.08 0.03;0.23 0.0000 1.0000 (0.00) 1 319
Stent thrombosis (any, end offollow up)
RR=0.20 0.02;1.65 0.1337 1.0000 (0.00) 1 322
angiographic restenosis RR=0.06 0.02;0.18 0.0000 1.0000 (1.00) 1 322
Table 19.5: Summary of all results for comparison versus CABG
Endpoint Effect 95% CI p ass p het (I2) k n
Paclitaxel eluting stent versus CABG
All cause death RR=1.25 0.79;1.98 0.3448 1.0000 (1.00) 1 1800
MI (fatal and non fatal) RR=1.47 0.93;2.34 0.1003 1.0000 (0.00) 1 1800
MACE RR=1.47 1.17;1.84 0.0000 1.0000 (0.00) 1 1800
target lesion revascularisation RR=2.32 1.71;3.16 0.0000 1.0000 (0.00) 1 1800
Table 19.6: Summary of all results for comparison versus paclitaxel eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Genous stent versus paclitaxel eluting stent
MI (fatal and non fatal) RR=0.19 0.02;1.63 0.1309 1.0000 (0.00) 1 193
target lesion revascularisation RR=1.33 0.56;3.17 0.5154 1.0000 (0.00) 1 193
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.83 0.47;1.47 0.5323 0.7083 (0.00) 4 1322
cardiac death RR=2.00 0.07;59.35 0.6886 1.0000 (0.00) 1 500
MI (fatal and non fatal) RR=0.80 0.54;1.20 0.2848 0.9971 (0.00) 4 1322
target-vessel revascularization RR=0.42 0.19;0.94 0.0357 1.0000 (0.00) 1 500
target lesion revascularisation RR=0.62 0.42;0.93 0.0213 0.3870 (0.01) 4 1322
Stent thrombosis (any, end offollow up)
RR=0.83 0.24;2.85 0.7641 0.7074 (0.00) 4 1322
4y stent thrombosis (ARC) RR=0.45 0.14;1.40 0.1655 0.8107 (0.00) 4 1322
angiographic restenosis RR=0.25 0.10;0.60 0.0020 1.0000 (0.00) 1 500
19.4. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS183
Figure 19.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.79 [0.30;2.07] .63 2 1602 .46 0.00
Sirolimus eluting stent versus bare-metalstent
0.97 [0.06;15.36] .98 1 319 1.00 0.00
comparison versus CABG
Paclitaxel eluting stent versus CABG 1.25 [0.79;1.98] .34 1 1800 1.00 1.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.83 [0.47;1.47] .53 4 1322 .71 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 19.2: Forest’s plot for cardiac death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus CABG
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
2.00 [0.07;59.35] .69 1 500 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
184CHAPTER 19. OVERVIEW OF AVAILABLE EVIDENCE FOR LONG OR COMPLEX LESION
Figure 19.3: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
1.16 [0.71;1.88] .56 2 1602 .89 0.00
comparison versus CABG
Paclitaxel eluting stent versus CABG 1.47 [0.93;2.34] .10 1 1800 1.00 0.00
comparison versus paclitaxel eluting stent
Genous stent versus paclitaxel elutingstent
0.19 [0.02;1.63] .13 1 193 1.00 0.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.80 [0.54;1.20] .28 4 1322 1.00 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 19.4: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.71 [0.58;0.88] .00 2 1602 .86 0.00
Sirolimus eluting stent versus bare-metalstent
0.10 [0.04;0.25] .00 1 322 1.00 0.00
comparison versus CABG
Paclitaxel eluting stent versus CABG 1.47 [1.17;1.84] .00 1 1800 1.00 0.00
comparison versus paclitaxel eluting stent
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
19.4. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS185
Figure 19.5: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.70 [0.53;0.93] .01 1 1156 1.00 0.00
comparison versus CABG
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.42 [0.19;0.94] .04 1 500 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 19.6: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.55 [0.39;0.77] .00 1 1156 1.00 0.00
Sirolimus eluting stent versus bare-metalstent
0.08 [0.03;0.23] .00 1 319 1.00 0.00
comparison versus CABG
Paclitaxel eluting stent versus CABG 2.32 [1.71;3.16] .00 1 1800 1.00 0.00
comparison versus paclitaxel eluting stent
Genous stent versus paclitaxel elutingstent
1.33 [0.56;3.17] .52 1 193 1.00 0.00
Sirolimus eluting stent versus paclitaxeleluting stent
0.62 [0.42;0.93] .02 4 1322 .39 0.01
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
186CHAPTER 19. OVERVIEW OF AVAILABLE EVIDENCE FOR LONG OR COMPLEX LESION
Figure 19.7: Forest’s plot for stent thrombosis (any, end of follow up)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.75 [0.23;2.45] .64 2 1602 .43 0.00
Sirolimus eluting stent versus bare-metalstent
0.20 [0.02;1.65] .13 1 322 1.00 0.00
comparison versus CABG
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.83 [0.24;2.85] .76 4 1322 .71 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 19.8: Forest’s plot for 4y stent thrombosis (ARC)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
comparison versus CABG
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.45 [0.14;1.40] .17 4 1322 .81 0.00
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
19.4. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS187
Figure 19.9: Forest’s plot for acute stent thrombosis (<=24h)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
3.01 [0.31;29.04] .34 1 1156 1.00 0.00
comparison versus CABG
comparison versus paclitaxel eluting stent
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 19.10: Forest’s plot for sub acute stent thrombosis (1-30 days)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.34 [0.04;3.04] .33 1 1156 1.00 0.00
comparison versus CABG
comparison versus paclitaxel eluting stent
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
188CHAPTER 19. OVERVIEW OF AVAILABLE EVIDENCE FOR LONG OR COMPLEX LESION
Figure 19.11: Forest’s plot for angiographic restenosis
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.43 [0.33;0.56] .00 1 1156 1.00 1.00
Sirolimus eluting stent versus bare-metalstent
0.06 [0.02;0.18] .00 1 322 1.00 1.00
comparison versus CABG
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.25 [0.10;0.60] .00 1 500 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
189
20 Detailed results for comparison versus bare-metal
stent in long or complex lesion
20.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
A total of 3 RCTs which randomized 1924 patients were identified: 2 trials compared pa-clitaxel eluting stent with bare-metal stent and 1 trial compared sirolimus eluting stent withbare-metal stent (see 20.1 page 190).
The average study size was 641 patients per arm (range 159 to 579 per arm). The first studywas published in 2005, and the last study was published in 2006. 2 trials were double blind and1 were open-label in design. All included studies were reported in English language. We did notfound any unpublished trial.
MACE data was reported in 3 trials; 3 trials reported data on angiographic restenosis ; 2trials reported data on All cause death; 1 trials reported data on target lesion revascularisation ;1 trials reported data on MI (fatal and non fatal); and 3 trials reported data on Stent thrombosis(any, end of follow up).
Following table 20.1 (page 190) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus bare-metal stent.
190 CHAPTER 20. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Table
20.1
:M
ain
study
char
act
eris
tics
-lo
ng
orco
mple
xle
sion
-co
mpar
ison
ver
sus
bare
-met
alst
ent
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
TA
XU
SV
I,2005
[1,
2]
n=
219
vs.
227
Sta
ble
or
unst
able
AP
,si
lent
isch
aem
iaw
ith
long,
com
ple
xco
ronary
art
ery
lesi
ons
TA
XU
Svs.
Expre
ss2
sten
tdouble
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:T
VR
44
centr
es,
Euro
pe
TA
XU
SV
(all
pati
ents
),2005
[3]
n=
577
vs.
579
Sta
ble
or
unst
able
AP
,si
lent
isch
aem
iaw
ith
single
coro
nary
art
ery
sten
osi
sin
cludin
gco
mple
xor
pre
vio
usl
yunst
udie
dle
sions
(req
uir
ing
2.2
5-m
m,
4.0
-mm
,and/or
mult
iple
sten
ts)
TA
XU
Svs.
bare
met
al
EX
PR
ESS-2
double
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:T
VR
66
centr
es,
Unit
edSta
tes
QC
Afo
llow
-up
dura
tion:
9m
o
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
SC
AN
DST
EN
T,
2006
[4,
5]
n=
163
vs.
159
Sta
ble
or
unst
able
AP
,re
cent
AM
I(n
on
ST
-ele
vati
on);
wit
hone
or
more
de
nov
oco
mple
xle
sions
innati
ve
coro
nary
ves
sels
(occ
luded
,bif
urc
ati
onal,
ost
ial
or
angula
ted)
Cypher
vs.
Sonic
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:M
inim
al
lum
endia
me-
ter
4ce
ntr
es,
Den
mark
20.2. META-ANALYSIS RESULTS 191
20.2 Meta-analysis results
The results are detailed in table 20.2 (page 192). This table is followed by the Forest’s plotcorresponding to each endpoint.
Paclitaxel eluting stent versus bare-metal stent
All the 2 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between paclitaxeleluting stent and bare-metal stent, with a RR of 0.79 (95%CI 0.30 to 2.07, p=0.6308) in favourof paclitaxel eluting stent. In other words, all cause death was slightly lower in the paclitaxeleluting stent group , but this was not statistically significant. No heterogeneity across thesetrials was detected (p =0.4575, I2 = 0.00%).
All the 2 studies had extractable data about the number of participants with MI (fatal andnon fatal). When pooled together, there was no statistically significant difference between thegroups in MI (fatal and non fatal), with a RR of 1.16 (95% CI 0.71 to 1.88, p=0.5584). Noheterogeneity across these trials was detected (p =0.8870, I2 = 0.00%).
All the 2 studies had extractable data about the number of participants with MACE. Theanalysis detected a statistically significant difference in favor of paclitaxel eluting stent in MACE,with a RR of 0.71 (95% CI 0.58 to 0.88, p=0.0016). No heterogeneity across these trials wasdetected (p =0.8622, I2 = 0.00%).
Only one of the 2 studies eligible for this comparison provided data on target-vesselrevascularization. The analysis detected a statistically significant difference in favor of pacli-taxel eluting stent in target-vessel revascularization, with a RR of 0.70 (95% CI 0.53 to 0.93,p=0.0145).
Only one of the 2 studies eligible for this comparison provided data on target lesion revas-cularisation . The analysis detected a statistically significant difference in favor of pacli-taxel eluting stent in target lesion revascularisation , with a RR of 0.55 (95% CI 0.39 to 0.77,p=0.0000).
Only one of the 2 studies eligible for this comparison provided data on angiographicrestenosis . The analysis detected a statistically significant difference in favor of paclitaxeleluting stent in angiographic restenosis , with a RR of 0.43 (95% CI 0.33 to 0.56, p=0.0000).
Sirolimus eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 0.97 (95%CI 0.06 to 15.36, p=0.9823) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of0.10 (95% CI 0.04 to 0.25, p=0.0000).
The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target lesion revascularisation , with a RR of 0.08 (95% CI 0.03 to 0.23, p=0.0000).
The single study eligible for this comparison provided data on angiographic restenosis .The analysis detected a statistically significant difference in favor of sirolimus eluting stent inangiographic restenosis , with a RR of 0.06 (95% CI 0.02 to 0.18, p=0.0000).
192 CHAPTER 20. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Table 20.2: Results details - long or complex lesion - comparison versus bare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=0.79 [0.30;2.07] 0.6308 0.4575 (I=0.00) 2 1602
MI (fatal and non fatal) RR=1.16 [0.71;1.88] 0.5584 0.8870 (I=0.00) 2 1602
MACE RR=0.71 [0.58;0.88] 0.0016 0.8622 (I=0.00) 2 1602
target-vessel revascularization RR=0.70 [0.53;0.93] 0.0145 1.0000 (I=0.00) 1 1156
target lesion revascularisation RR=0.55 [0.39;0.77] 0.0000 1.0000 (I=0.00) 1 1156
Stent thrombosis (any, end offollow up)
RR=0.75 [0.23;2.45] 0.6369 0.4273 (I=0.00) 2 1602
Acute stent thrombosis(<=24h)
RR=3.01 [0.31;29.04] 0.3407 1.0000 (I=0.00) 1 1156
sub acute stent thrombosis(1-30 days)
RR=0.34 [0.04;3.04] 0.3347 1.0000 (I=0.00) 1 1156
angiographic restenosis RR=0.43 [0.33;0.56] 0.0000 1.0000 (I=1.00) 1 1156
Sirolimus eluting stent versus bare-metal stent
All cause death RR=0.97 [0.06;15.36] 0.9823 1.0000 (I=0.00) 1 319
MACE RR=0.10 [0.04;0.25] 0.0000 1.0000 (I=0.00) 1 322
target lesion revascularisation RR=0.08 [0.03;0.23] 0.0000 1.0000 (I=0.00) 1 319
Stent thrombosis (any, end offollow up)
RR=0.20 [0.02;1.65] 0.1337 1.0000 (I=0.00) 1 322
angiographic restenosis RR=0.06 [0.02;0.18] 0.0000 1.0000 (I=1.00) 1 322
Figure 20.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS VI,2005 0/219 2/227 0.26 [0.01;5.71]
TAXUS V (all patients),20 /577 /579 0.89 [0.32;2.45]
Global p ass= 0.6308 0.79 [0.30;2.07]
Het. between 2 trials p=0.4575 I2=0.00
Sirolimus eluting stent versus bare-metal stent
SCANDSTENT,2006 1/162 1/157 0.97 [0.06;15.36]
Global p ass= 0.9823 0.97 [0.06;15.36]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
20.2. META-ANALYSIS RESULTS 193
Figure 20.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS VI,2005 3/219 3/227 1.04 [0.21;5.08]
TAXUS V (all patients),20 /577 /579 1.17 [0.70;1.95]
Global p ass= 0.5584 1.16 [0.71;1.88]
Het. between 2 trials p=0.8870 I2=0.00
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 20.3: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS VI,2005 36/219 51/227 0.73 [0.50;1.07]
TAXUS V (all patients),20 84/577 120/579 0.70 [0.54;0.91]
Global p ass= 0.0016 0.71 [0.58;0.88]
Het. between 2 trials p=0.8622 I2=0.00
Sirolimus eluting stent versus bare-metal stent
SCANDSTENT,2006 5/163 48/159 0.10 [0.04;0.25]
Global p ass= 0.0000 0.10 [0.04;0.25]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 20.4: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS V (all patients),20 /577 /579 0.70 [0.53;0.93]
Global p ass= 0.0145 0.70 [0.53;0.93]
1.00.90.80.70.60.50.50.10.20.30.40.5 0.6 0.7 0.8 0.9 1.0Relative risk
treatment worsens outcometreatment improves outcome
194 CHAPTER 20. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 20.5: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS V (all patients),20 /577 /579 0.55 [0.39;0.77]
Global p ass= 0.0000 0.55 [0.39;0.77]
Sirolimus eluting stent versus bare-metal stent
SCANDSTENT,2006 4/162 46/157 0.08 [0.03;0.23]
Global p ass= 0.0000 0.08 [0.03;0.23]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 20.6: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS VI,2005 1/219 3/227 0.35 [0.04;3.30]
TAXUS V (all patients),20 /577 /579 1.01 [0.25;4.05]
Global p ass= 0.6369 0.75 [0.23;2.45]
Het. between 2 trials p=0.4273 I2=0.00
Sirolimus eluting stent versus bare-metal stent
SCANDSTENT,2006 1/163 5/159 0.20 [0.02;1.65]
Global p ass= 0.1337 0.20 [0.02;1.65]
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
20.2. META-ANALYSIS RESULTS 195
Figure 20.7: Forest’s plot for acute stent thrombosis (<=24h)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS V (all patients),20 /577 /579 3.01 [0.31;29.04]
Global p ass= 0.3407 3.01 [0.31;29.04]
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 20.8: Forest’s plot for sub acute stent thrombosis (1-30 days)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS V (all patients),20 /577 /579 0.34 [0.04;3.04]
Global p ass= 0.3347 0.34 [0.04;3.04]
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 20.9: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
TAXUS V (all patients),20 /577 /579 0.43 [0.33;0.56]
Global p ass= 0.0000 0.43 [0.33;0.56]
Sirolimus eluting stent versus bare-metal stent
SCANDSTENT,2006 3/163 51/159 0.06 [0.02;0.18]
Global p ass= 0.0000 0.06 [0.02;0.18]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
196 REFERENCES
References
[1] Dawkins KD, Grube E, Guagliumi G, Banning AP, Zmudka K, Colombo A, Thuesen L, Hauptman K, MarcoJ, Wijns W, Popma JJ, Koglin J, Russell ME. Clinical efficacy of polymer-based paclitaxel-eluting stents inthe treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for theuse of drug-eluting stents in contemporary clinical practice.. Circulation 2005;112:3306-13 [PMID=16286586]
[2] Grube E, Dawkins KD, Guagliumi G, Banning AP, Zmudka K, Colombo A, Thuesen L, Hauptman K,Marco J, Wijns W, Popma JJ, Buellesfeld L, Koglin J, Russell ME. TAXUS VI 2-year follow-up: randomizedcomparison of polymer-based paclitaxel-eluting with bare metal stents for treatment of long, complex lesions..Eur Heart J 2007;28:2578-82 [PMID=17938126]
[3] Stone GW, Ellis SG, Cannon L, Mann JT, Greenberg JD, Spriggs D, O’Shaughnessy CD, DeMaio S, Hall P,Popma JJ, Koglin J, Russell ME. Comparison of a polymer-based paclitaxel-eluting stent with a bare metalstent in patients with complex coronary artery disease: a randomized controlled trial.. JAMA 2005;294:1215-23 [PMID=16160130]
[4] Kelbaek H, Thuesen L, Helqvist S, Klvgaard L, Jrgensen E, Aljabbari S, Saunamki K, Krusell LR, Jensen GV,Btker HE, Lassen JF, Andersen HR, Thayssen P, Galle A, van Weert A. The Stenting Coronary Arteries inNon-stress/benestent Disease (SCANDSTENT) trial.. J Am Coll Cardiol 2006;47:449-55 [PMID=16412876]
[5] Kelbaek H, Klvgaard L, Helqvist S, Lassen JF, Krusell LR, Engstrm T, Btker HE, Jrgensen E, SaunamkiK, Aljabbari S, Thayssen P, Galle A, Jensen GV, Thuesen L. Long-term outcome in patients treated withsirolimus-eluting stents in complex coronary artery lesions: 3-year results of the SCANDSTENT (Stent-ing Coronary Arteries in Non-Stress/Benestent Disease) trial.. J Am Coll Cardiol 2008 May 27;51:2011-6[PMID=18498953]
197
21 Detailed results for comparison versus CABG in
long or complex lesion
21.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus CABGOnly one trial which randomized 1800 patients was identified: all compared paclitaxel eluting
stent with CABG (see 21.1 page 198).The average study size was 1800 patients per arm (range 897 to 903 per arm). The first
study was published in , and the last study was published in .All trials were open-label in design. All included studies were reported in English language.
We did not found any unpublished trial.Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI
(fatal and non fatal); 1 trials reported data on MACE; and 1 trials reported data on All causedeath.
Following table 21.1 (page 198) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus CABG.
198 CHAPTER 21. DETAILS FOR COMPARISON VERSUS CABG
Table
21.1
:M
ain
study
char
acte
rist
ics
-lo
ng
orco
mple
xle
sion
-co
mpar
ison
vers
us
CA
BG
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Paclita
xelelu
ting
stentvers
us
CA
BG
SY
NT
AX
,0
[]n
=903
vs.
897
pati
ents
wit
hco
mple
xco
ronary
dis
ease
pacl
itaxel
(taxus
Expre
ssSR
)vs.
Coro
nary
Art
ery
Bypass
Surg
ery
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:M
AC
E,
21.2. META-ANALYSIS RESULTS 199
21.2 Meta-analysis results
The results are detailed in table 21.2 (page 199). This table is followed by the Forest’s plotcorresponding to each endpoint.
Paclitaxel eluting stent versus CABG
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between paclitaxel eluting stent andCABG, with a RR of 1.25 (95%CI 0.79 to 1.98, p=0.3448) in favour of CABG. In other words,all cause death was slightly lower in the CABG group , but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 1.47 (95% CI 0.93 to 2.34, p=0.1003).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of CABG in MACE, with a RR of 1.47 (95% CI 1.17to 1.84, p=0.0000).
The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of CABG in targetlesion revascularisation , with a RR of 2.32 (95% CI 1.71 to 3.16, p=0.0000).
Table 21.2: Results details - long or complex lesion - comparison versus CABG
Comparison Endpoint Effect 95% CI p ass hom k n
Paclitaxel eluting stent versus CABG
All cause death RR=1.25 [0.79;1.98] 0.3448 1.0000 (I=1.00) 1 1800
MI (fatal and non fatal) RR=1.47 [0.93;2.34] 0.1003 1.0000 (I=0.00) 1 1800
MACE RR=1.47 [1.17;1.84] 0.0000 1.0000 (I=0.00) 1 1800
target lesion revascularisation RR=2.32 [1.71;3.16] 0.0000 1.0000 (I=0.00) 1 1800
Figure 21.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus CABG
SYNTAX 39/903 31/897 1.25 [0.79;1.98]
Global p ass= 0.3448 1.25 [0.79;1.98]
1.00.80.5 1.0 1.5 2.0Relative risk
treatment worsens outcometreatment improves outcome
200 CHAPTER 21. DETAILS FOR COMPARISON VERSUS CABG
Figure 21.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus CABG
SYNTAX 43/903 29/897 1.47 [0.93;2.34]
Global p ass= 0.1003 1.47 [0.93;2.34]
1.00.8 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 21.3: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus CABG
SYNTAX 161/903 109/897 1.47 [1.17;1.84]
Global p ass= 0.0000 1.47 [1.17;1.84]
1.00.51.0 1.5 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 21.4: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus CABG
SYNTAX 124/903 53/897 2.32 [1.71;3.16]
Global p ass= 0.0000 2.32 [1.71;3.16]
1.0 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 201
References
202CHAPTER 22. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
22 Detailed results for comparison versus paclitaxel
eluting stent in long or complex lesion
22.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent
A total of 5 RCTs which randomized 1515 patients were identified: 1 trial compared Genousstent with paclitaxel eluting stent and 4 trials compared sirolimus eluting stent with paclitaxeleluting stent (see 22.1 page 203).
The average study size was 303 patients per arm (range 33 to 331 per arm). The first studywas published in 2005, and the last study was published in 2008.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target lesion revascularisation data was reported in 5 trials; 5 trials reported data on MI(fatal and non fatal); 4 trials reported data on All cause death; 1 trials reported data ontarget-vessel revascularization; 1 trials reported data on cardiac death; 1 trials reported data onangiographic restenosis ; 4 trials reported data on Stent thrombosis (any, end of follow up); and4 trials reported data on 4y stent thrombosis (ARC).
Following table 22.1 (page 203) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus paclitaxel eluting stent.
22.1. AVAILABLE RCTS 203
Table
22.1
:M
ain
study
chara
cter
isti
cs-
long
orco
mple
xle
sion
-co
mpar
ison
ver
sus
pacl
itaxel
eluti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Genous
stentvers
us
paclita
xelelu
ting
stent
TR
IAS-H
R,
2008
[]n
=98
vs.
95
hig
h-r
isk
pati
ents
(long
lesi
ons,
small
ves
sels
,ch
ronic
tota
locc
lusi
ons,
or
any
lesi
on
ina
dia
bet
icpati
ent)
Gen
ous
sten
t(a
nti
body-c
oate
dbare
-met
al
sten
t)fo
llow
edby
one
month
of
dual
anti
pla
tele
tth
erapy
vs.
Taxus
or
Cypher
follow
edby
at
least
six
month
sof
dual
anti
pla
tele
tth
erapy
single
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:ta
rget
lesi
on
failure
single
cente
r,
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Pet
ronio
etal,
2007
[1]
n=
50
vs.
50
Com
ple
xle
sions.
Sta
ble
AP
or
docu
men
ted
isch
aem
ia,
no
AM
IC
ypher
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:N
eoin
tim
al
hyp
erpla
sia
single
cente
r,It
aly
Cer
vin
ka,
2006
[2]
n=
37
vs.
33
Com
ple
xle
sionsa
nd
pati
ents
.Sig
ns
and/or
sym
pto
ms
myoca
rdia
lis
chaem
ia,
incl
udin
gA
MI
siro
lim
us-
eluti
ng
sten
tvs.
pacl
itaxel
-elu
ting
sten
top
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:N
eoin
tim
al
hyp
erpla
sia
1ce
ntr
es,
LO
NG
DE
SII
,2006
[3]
n=
250
vs.
250
Long
lesi
ons.
AP
or
posi
tive
stre
ss,
no
AM
ISE
Svs.
PE
Ssi
ngle
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s5
centr
es,
Kore
a
CO
RP
AL
,2005
[4]
n=
331
vs.
321
Docu
men
ted
myoca
rdia
lis
chaem
ia,
no
AM
Isi
rolim
us
vs.
pacl
itaxel
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s2
centr
es,
Spain
204CHAPTER 22. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
22.2 Meta-analysis results
The results are detailed in table 22.2 (page 204). This table is followed by the Forest’s plotcorresponding to each endpoint.
Genous stent versus paclitaxel eluting stent
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 0.19 (95% CI 0.02 to 1.63, p=0.1309).
The single study eligible for this comparison provided data on target lesion revascular-isation . No statistically significant difference between the groups was found in target lesionrevascularisation , with a RR of 1.33 (95% CI 0.56 to 3.17, p=0.5154).
Sirolimus eluting stent versus paclitaxel eluting stent
All the 4 studies had extractable data about the number of participants with all causedeath. There was no statistically significant difference in all cause death between sirolimuseluting stent and paclitaxel eluting stent, with a RR of 0.83 (95%CI 0.47 to 1.47, p=0.5323)in favour of sirolimus eluting stent. In other words, all cause death was slightly lower in thesirolimus eluting stent group , but this was not statistically significant. No heterogeneity acrossthese trials was detected (p =0.7083, I2 = 0.00%).
Only one of the 4 studies eligible for this comparison provided data on cardiac death. Nostatistically significant difference between the groups was found in cardiac death, with a RR of2.00 (95% CI 0.07 to 59.35, p=0.6886).
All the 4 studies had extractable data about the number of participants with MI (fatal andnon fatal). When pooled together, there was no statistically significant difference between thegroups in MI (fatal and non fatal), with a RR of 0.80 (95% CI 0.54 to 1.20, p=0.2848). Noheterogeneity across these trials was detected (p =0.9971, I2 = 0.00%).
Only one of the 4 studies eligible for this comparison provided data on target-vessel revas-cularization. The analysis detected a statistically significant difference in favor of sirolimuseluting stent in target-vessel revascularization, with a RR of 0.42 (95% CI 0.19 to 0.94, p=0.0357).
All the 4 studies had extractable data about the number of participants with target le-sion revascularisation . The analysis detected a statistically significant difference in favor ofsirolimus eluting stent in target lesion revascularisation , with a RR of 0.62 (95% CI 0.42 to0.93, p=0.0213). No heterogeneity across these trials was detected (p =0.3870, I2 = 0.01%).
Only one of the 4 studies eligible for this comparison provided data on angiographicrestenosis . The analysis detected a statistically significant difference in favor of sirolimuseluting stent in angiographic restenosis , with a RR of 0.25 (95% CI 0.10 to 0.60, p=0.0020).
Table 22.2: Results details - long or complex lesion - comparison versus paclitaxel eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
Genous stent versus paclitaxel eluting stent
MI (fatal and non fatal) RR=0.19 [0.02;1.63] 0.1309 1.0000 (I=0.00) 1 193
target lesion revascularisation RR=1.33 [0.56;3.17] 0.5154 1.0000 (I=0.00) 1 193
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.83 [0.47;1.47] 0.5323 0.7083 (I=0.00) 4 1322
cardiac death RR=2.00 [0.07;59.35] 0.6886 1.0000 (I=0.00) 1 500
MI (fatal and non fatal) RR=0.80 [0.54;1.20] 0.2848 0.9971 (I=0.00) 4 1322
continued...
22.2. META-ANALYSIS RESULTS 205
Comparison Endpoint Effect 95% CI p ass hom k n
target-vessel revascularization RR=0.42 [0.19;0.94] 0.0357 1.0000 (I=0.00) 1 500
target lesion revascularisation RR=0.62 [0.42;0.93] 0.0213 0.3870 (I=0.01) 4 1322
Stent thrombosis (any, end offollow up)
RR=0.83 [0.24;2.85] 0.7641 0.7074 (I=0.00) 4 1322
4y stent thrombosis (ARC) RR=0.45 [0.14;1.40] 0.1655 0.8107 (I=0.00) 4 1322
angiographic restenosis RR=0.25 [0.10;0.60] 0.0020 1.0000 (I=0.00) 1 500
Figure 22.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Petronio et al,2007 1/50 2/50 0.50 [0.05;5.34]
Cervinka,2006 1/37 0/33 1.78 [0.06;51.47]
LONG DES II,2006 2/250 0/250 4.00 [0.18;88.27]
CORPAL,2005 18/331 22/321 0.79 [0.43;1.45]
Global p ass= 0.5323 0.83 [0.47;1.47]
Het. between 4 trials p=0.7083 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 22.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
LONG DES II,2006 1/250 0/250 2.00 [0.07;59.35]
Global p ass= 0.6886 2.00 [0.07;59.35]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
206CHAPTER 22. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Figure 22.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Genous stent versus paclitaxel eluting stent
TRIAS-HR,2008 1/98 5/95 0.19 [0.02;1.63]
Global p ass= 0.1309 0.19 [0.02;1.63]
Sirolimus eluting stent versus paclitaxel eluting stent
Petronio et al,2007 1/50 1/50 1.00 [0.06;15.55]
Cervinka,2006 1/37 1/33 0.89 [0.06;13.70]
LONG DES II,2006 21/250 27/250 0.78 [0.45;1.34]
CORPAL,2005 17/331 20/321 0.82 [0.44;1.54]
Global p ass= 0.2848 0.80 [0.54;1.20]
Het. between 4 trials p=0.9971 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 22.4: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
LONG DES II,2006 8/250 19/250 0.42 [0.19;0.94]
Global p ass= 0.0357 0.42 [0.19;0.94]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
22.2. META-ANALYSIS RESULTS 207
Figure 22.5: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Genous stent versus paclitaxel eluting stent
TRIAS-HR,2008 11/98 8/95 1.33 [0.56;3.17]
Global p ass= 0.5154 1.33 [0.56;3.17]
Sirolimus eluting stent versus paclitaxel eluting stent
Petronio et al,2007 2/50 2/50 1.00 [0.15;6.82]
Cervinka,2006 1/37 3/33 0.30 [0.03;2.72]
LONG DES II,2006 6/250 18/250 0.33 [0.13;0.83]
CORPAL,2005 29/331 38/321 0.74 [0.47;1.17]
Global p ass= 0.0213 0.62 [0.42;0.93]
Het. between 4 trials p=0.3870 I2=0.01
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 22.6: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Petronio et al,2007 0/50 0/50 1.00 [0.02;49.42]
Cervinka,2006 1/37 1/33 0.89 [0.06;13.70]
LONG DES II,2006 2/250 0/250 4.00 [0.18;88.27]
CORPAL,2005 2/331 4/321 0.48 [0.09;2.63]
Global p ass= 0.7641 0.83 [0.24;2.85]
Het. between 4 trials p=0.7074 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
208 REFERENCES
Figure 22.7: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Petronio et al,2007 0/50 0/50 1.00 [0.02;49.42]
Cervinka,2006 1/37 1/33 0.89 [0.06;13.70]
LONG DES II,2006 1/250 5/250 0.20 [0.02;1.70]
CORPAL,2005 2/331 4/321 0.48 [0.09;2.63]
Global p ass= 0.1655 0.45 [0.14;1.40]
Het. between 4 trials p=0.8107 I2=0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 22.8: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
LONG DES II,2006 6/250 24/250 0.25 [0.10;0.60]
Global p ass= 0.0020 0.25 [0.10;0.60]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Petronio AS, De Carlo M, Branchitta G, Papini B, Ciabatti N, Gistri R, Cortese B, Gherarducci G, BarsottiA. Randomized comparison of sirolimus and paclitaxel drug-eluting stents for long lesions in the left anteriordescending artery: an intravascular ultrasound study.. J Am Coll Cardiol 2007;49:539-46 [PMID=17276176]
[2] Cervinka P, Costa MA, Angiolillo DJ, Spacek R, Bystron M, Kvasnk M, Veselka J, Nanda H, Futamatsu H,Futamatsu K. ”Head-to-head comparison between sirolimus-eluting and paclitaxel-eluting stents in patientswith complex coronary artery disease: an intravascular ultrasound study”.. Catheter Cardiovasc Interv2006;67:846-51 [PMID=16683273]
[3] Kim YH, Park SW, Lee SW, Park DW, Yun SC, Lee CW, Hong MK, Kim HS, Ko JK, Park JH, Lee JH,Choi SW, Seong IW, Cho YH, Lee NH, Kim JH, Chun KJ, Park SJ. Sirolimus-eluting stent versus paclitaxel-eluting stent for patients with long coronary artery disease.. Circulation 2006;114:2148-53 [PMID=17060388]
REFERENCES 209
[4] de Lezo J, Medina A, Pan M, et al.. de Lezo J, Medina A, Pan M, et al. Drug-eluting stent for complexlesions:latest angiographic data from randomized rapamycinversus paclitaxel CORPAL study. J Am Coll Cardiol2005; 45: 75A.
210 REFERENCES
REFERENCES 211
23 Ongoing studies of long or complex lesion
23.1 List of ongoing trials
No ongoing trial was identified. still ongoing at the date of this report. A list of these ongoingstudies with a brief description is given table 23.1.
Table 23.1: Ongoing studies for long or complex lesion
Study Description
References
212 REFERENCES
Part VI
In-stent restenosis
213
214
215
24 Overview of available evidence for in-stent
restenosis
A total of 5 RCTs which randomized 1380 patients were identified. (see tables 24.1 to 24.3 )In all, 2 reports concerned comparison versus ballon angioplasty , 2 the comparison versus
brachytherapy and 1 the comparison versus paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 25 (page
225) for comparison versus ballon angioplasty, in section 26 (page 230 ) for comparison versusbrachytherapy and in section 27 (page 236 ) for comparison versus paclitaxel eluting stent.
The average study size was 276 patients per arm (range 100 to 259 per arm). The first studywas published in 2005, and the last study was published in 2007.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
216CHAPTER 24. OVERVIEW OF AVAILABLE EVIDENCE FOR IN-STENT RESTENOSIS
Table
24.1
:M
ain
study
chara
cter
isti
cs-
in-s
tent
rest
enos
is-
com
par
ison
vers
us
ballon
angio
pla
sty
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
ballon
angio
pla
sty
Paclita
xelelu
ting
stentvers
us
ballon
angio
pla
sty
ISA
R-D
ESIR
E(P
ES
vs
PT
CA
),2005
[1]
TA
XU
Svs.
ballon
angio
pla
sty
100
vs.
100
op
enP
ara
llel
gro
ups
Bin
ary
rest
enosi
sger
many
Sirolim
us
elu
ting
stentvers
us
ballon
angio
pla
sty
ISA
R-D
ESIR
E(S
ES
vs
PT
CA
),2005
[2]
Cypher
vs.
ballon
angio
pla
sty
100
vs.
100
op
enP
ara
llel
gro
ups
Bin
ary
rest
enosi
sger
many
217
Table
24.2
:M
ain
study
char
acte
rist
ics
-in
-ste
nt
rest
enos
is-
com
pari
son
vers
us
bra
chyth
erapy
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bra
chyth
era
py
Paclita
xelelu
ting
balloon
vers
us
bra
chyth
era
py
TA
XU
SV
ISR
,2006
[1]
TA
XU
SE
xpre
ss2
vs.
angio
pla
sty
follow
edby
vasc
ula
rbra
chyth
erapy
wit
ha
bet
aso
urc
e
195
vs.
201
op
enP
ara
llel
gro
ups
Isch
emia
-dri
ven
TV
Rat
9m
onth
sN
ort
hA
mer
ica
Sirolim
us
elu
ting
stentvers
us
bra
chyth
era
py
SIS
R,
2007
[2,
3]
Sir
olim
us-
eluti
ng
sten
tsvs.
bra
chyth
erapy
259
vs.
125
op
enP
ara
llel
gro
ups
targ
etves
sel
failure
US
and
Cana-
dia
n
218CHAPTER 24. OVERVIEW OF AVAILABLE EVIDENCE FOR IN-STENT RESTENOSIS
Table
24.3
:M
ain
study
chara
cter
isti
cs-
in-s
tent
rest
enos
is-
com
par
ison
vers
us
pacl
itaxel
eluti
ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
paclita
xel
elu
ting
stent
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
ISA
R-D
ESIR
E(S
ES
vs
PE
S),
2005
[1]
Cypher
vs.
Taxus
100
vs.
100
op
enP
ara
llel
gro
ups
Bin
ary
rest
enosi
sger
many
24.4. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS219
24.1 Main results for in-stent restenosis
The meta-analysis of the available trials provide the results listed in tables 24.4 to 24.6 (page219) and in the following graphs.
24.2 comparison versus ballon angioplasty - summary of results
Paclitaxel eluting stent was superior to ballon angioplasty in terms of target-vessel revas-cularization (RR=0.58, 95% CI 0.35 to 0.94, p=0.0278, 1 trial) .However, no significant differencewas found on all cause death (RR=0.33, 95% CI 0.04 to 3.15, p=0.3377, 1 trial) and MI (fataland non fatal) (RR=4.00, 95% CI 0.18 to 87.61, p=0.3787, 1 trial) .
Sirolimus eluting stent was superior to ballon angioplasty in terms of target-vesselrevascularization (RR=0.24, 95% CI 0.12 to 0.50, p=0.0000, 1 trial) .However, no significantdifference was found on all cause death (RR=0.67, 95% CI 0.11 to 3.90, p=0.6530, 1 trial) andMI (fatal and non fatal) (RR=2.00, 95% CI 0.07 to 58.95, p=0.6880, 1 trial) .
24.3 comparison versus brachytherapy - summary of results
Data were insufficient to compare Paclitaxel eluting balloon to brachytherapy. There wasan eligible trial but it did not provided sufficient information about the endpoints considered bythis meta-analysis.
Sirolimus eluting stent was superior to brachytherapy in terms of MACE (RR=0.52,95% CI 0.31 to 0.87, p=0.0131, 1 trial) , target-vessel revascularization (RR=0.50, 95% CI 0.31to 0.81, p=0.0050, 1 trial) , target lesion revascularisation (RR=0.44, 95% CI 0.26 to 0.76,p=0.0030, 1 trial) and CABG (RR=0.08, 95% CI 0.01 to 0.66, p=0.0190, 1 trial) .However, nosignificant difference was found on all cause death (RR=0.48, 95% CI 0.01 to 24.18, p=0.7153,1 trial) and MI (fatal and non fatal) (RR=6.76, 95% CI 0.39 to 118.12, p=0.1906, 1 trial) .
24.4 comparison versus paclitaxel eluting stent - summary ofresults
Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of target-vesselrevascularization (RR=0.42, 95% CI 0.19 to 0.92, p=0.0294, 1 trial) .However, no significantdifference was found on all cause death (RR=2.00, 95% CI 0.18 to 21.71, p=0.5688, 1 trial) andMI (fatal and non fatal) (RR=0.50, 95% CI 0.05 to 5.43, p=0.5688, 1 trial) .
Table 24.4: Summary of all results for comparison versus ballon angioplasty
Endpoint Effect 95% CI p ass p het (I2) k n
Paclitaxel eluting stent versus ballon angioplasty
All cause death RR=0.33 0.04;3.15 0.3377 1.0000 (0.00) 1 200
MI (fatal and non fatal) RR=4.00 0.18;87.61 0.3787 1.0000 (0.00) 1 200
target-vessel revascularization RR=0.58 0.35;0.94 0.0278 1.0000 (0.00) 1 200
Sirolimus eluting stent versus ballon angioplasty
All cause death RR=0.67 0.11;3.90 0.6530 1.0000 (0.00) 1 200
MI (fatal and non fatal) RR=2.00 0.07;58.95 0.6880 1.0000 (0.00) 1 200
target-vessel revascularization RR=0.24 0.12;0.50 0.0000 1.0000 (0.00) 1 200
220CHAPTER 24. OVERVIEW OF AVAILABLE EVIDENCE FOR IN-STENT RESTENOSIS
Table 24.5: Summary of all results for comparison versus brachytherapy
Endpoint Effect 95% CI p ass p het (I2) k n
Paclitaxel eluting balloon versus brachytherapy
No data were presented in the trial identified
Sirolimus eluting stent versus brachytherapy
All cause death RR=0.48 0.01;24.18 0.7153 1.0000 (0.00) 1 384
MI (fatal and non fatal) RR=6.76 0.39;118.12 0.1906 1.0000 (0.00) 1 384
MACE RR=0.52 0.31;0.87 0.0131 1.0000 (0.00) 1 384
target-vessel revascularization RR=0.50 0.31;0.81 0.0050 1.0000 (0.00) 1 384
target lesion revascularisation RR=0.44 0.26;0.76 0.0030 1.0000 (1.00) 1 384
CABG RR=0.08 0.01;0.66 0.0190 1.0000 (0.00) 1 384
Stent thrombosis (any, end offollow up)
RR=1.93 0.09;42.50 0.6767 1.0000 (0.00) 1 384
Table 24.6: Summary of all results for comparison versus paclitaxel eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=2.00 0.18;21.71 0.5688 1.0000 (0.00) 1 200
MI (fatal and non fatal) RR=0.50 0.05;5.43 0.5688 1.0000 (0.00) 1 200
target-vessel revascularization RR=0.42 0.19;0.92 0.0294 1.0000 (0.00) 1 200
Stent thrombosis (any, end offollow up)
RR=0.25 0.01;5.48 0.3787 1.0000 (0.00) 1 200
4y stent thrombosis (ARC) RR=0.25 0.01;5.48 0.3787 1.0000 (0.00) 1 200
Figure 24.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
Paclitaxel eluting stent versus ballon an-gioplasty
0.33 [0.04;3.15] .34 1 200 1.00 0.00
Sirolimus eluting stent versus ballon an-gioplasty
0.67 [0.11;3.90] .65 1 200 1.00 0.00
comparison versus brachytherapy
Sirolimus eluting stent versusbrachytherapy
0.48 [0.01;24.18] .72 1 384 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
2.00 [0.18;21.71] .57 1 200 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
24.4. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS221
Figure 24.2: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
Paclitaxel eluting stent versus ballon an-gioplasty
4.00 [0.18;87.61] .38 1 200 1.00 0.00
Sirolimus eluting stent versus ballon an-gioplasty
2.00 [0.07;58.95] .69 1 200 1.00 0.00
comparison versus brachytherapy
Sirolimus eluting stent versusbrachytherapy
6.76 [0.39;118.12] .19 1 384 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.50 [0.05;5.43] .57 1 200 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 24.3: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
comparison versus brachytherapy
Sirolimus eluting stent versusbrachytherapy
0.52 [0.31;0.87] .01 1 384 1.00 0.00
comparison versus paclitaxel eluting stent
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
222CHAPTER 24. OVERVIEW OF AVAILABLE EVIDENCE FOR IN-STENT RESTENOSIS
Figure 24.4: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
Paclitaxel eluting stent versus ballon an-gioplasty
0.58 [0.35;0.94] .03 1 200 1.00 0.00
Sirolimus eluting stent versus ballon an-gioplasty
0.24 [0.12;0.50] .00 1 200 1.00 0.00
comparison versus brachytherapy
Sirolimus eluting stent versusbrachytherapy
0.50 [0.31;0.81] .01 1 384 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.42 [0.19;0.92] .03 1 200 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 24.5: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
comparison versus brachytherapy
Sirolimus eluting stent versusbrachytherapy
0.44 [0.26;0.76] .00 1 384 1.00 1.00
comparison versus paclitaxel eluting stent
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
24.4. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS223
Figure 24.6: Forest’s plot for CABG
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
comparison versus brachytherapy
Sirolimus eluting stent versusbrachytherapy
0.08 [0.01;0.66] .02 1 384 1.00 0.00
comparison versus paclitaxel eluting stent
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 24.7: Forest’s plot for stent thrombosis (any, end of follow up)
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
comparison versus brachytherapy
Sirolimus eluting stent versusbrachytherapy
1.93 [0.09;42.50] .68 1 384 1.00 0.00
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.25 [0.01;5.48] .38 1 200 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
224CHAPTER 24. OVERVIEW OF AVAILABLE EVIDENCE FOR IN-STENT RESTENOSIS
Figure 24.8: Forest’s plot for 4y stent thrombosis (ARC)
RR [95%CI] p k n p het I2
comparison versus ballon angioplasty
comparison versus brachytherapy
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.25 [0.01;5.48] .38 1 200 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
225
25 Detailed results for comparison versus ballon
angioplasty in in-stent restenosis
25.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus ballon an-gioplasty
A total of 2 RCTs which randomized 400 patients were identified: 1 trial compared paclitaxeleluting stent with ballon angioplasty and 1 trial compared sirolimus eluting stent with ballonangioplasty (see 25.1 page 226).
The average study size was 200 patients per arm (range 100 to 100 per arm). The first studywas published in 2005, and the last study was published in 2005.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target-vessel revascularization data was reported in 2 trials; 2 trials reported data on MI(fatal and non fatal); and 2 trials reported data on All cause death.
Following table 25.1 (page 226) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus ballon angioplasty.
226 CHAPTER 25. DETAILS FOR COMPARISON VERSUS BALLON ANGIOPLASTY
Table
25.1
:M
ain
study
chara
cter
isti
cs-
in-s
tent
rest
enos
is-
com
par
ison
vers
us
ballon
angio
pla
sty
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Paclita
xelelu
ting
stentvers
us
ballon
angio
pla
sty
ISA
R-D
ESIR
E(P
ES
vs
PT
CA
),2005
[1]
n=
100
vs.
100
In-s
tent
rest
enosi
s.A
Pand/or
posi
tive
test
,pre
vio
usl
yst
ente
d,
no
AM
IT
AX
US
vs.
ballon
angio
pla
sty
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s2
centr
es,
ger
many
Sirolim
us
elu
ting
stentvers
us
ballon
angio
pla
sty
ISA
R-D
ESIR
E(S
ES
vs
PT
CA
),2005
[2]
n=
100
vs.
100
In-s
tent
rest
enosi
s.A
Pand/or
posi
tive
test
,pre
vio
usl
yst
ente
d,
no
AM
IC
ypher
vs.
ballon
angio
pla
sty
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s2
centr
es,
ger
many
25.2. META-ANALYSIS RESULTS 227
25.2 Meta-analysis results
The results are detailed in table 25.2 (page 227). This table is followed by the Forest’s plotcorresponding to each endpoint.
Paclitaxel eluting stent versus ballon angioplasty
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between paclitaxel eluting stent andballon angioplasty, with a RR of 0.33 (95%CI 0.04 to 3.15, p=0.3377) in favour of paclitaxeleluting stent. In other words, all cause death was slightly lower in the paclitaxel eluting stentgroup , but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 4.00 (95% CI 0.18 to 87.61, p=0.3787).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of paclitaxel elutingstent in target-vessel revascularization, with a RR of 0.58 (95% CI 0.35 to 0.94, p=0.0278).
Sirolimus eluting stent versus ballon angioplasty
The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between sirolimus eluting stent and ballonangioplasty, with a RR of 0.67 (95%CI 0.11 to 3.90, p=0.6530) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 2.00 (95% CI 0.07 to 58.95, p=0.6880).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target-vessel revascularization, with a RR of 0.24 (95% CI 0.12 to 0.50, p=0.0000).
Table 25.2: Results details - in-stent restenosis - comparison versus ballon angioplasty
Comparison Endpoint Effect 95% CI p ass hom k n
Paclitaxel eluting stent versus ballon angioplasty
All cause death RR=0.33 [0.04;3.15] 0.3377 1.0000 (I=0.00) 1 200
MI (fatal and non fatal) RR=4.00 [0.18;87.61] 0.3787 1.0000 (I=0.00) 1 200
target-vessel revascularization RR=0.58 [0.35;0.94] 0.0278 1.0000 (I=0.00) 1 200
Sirolimus eluting stent versus ballon angioplasty
All cause death RR=0.67 [0.11;3.90] 0.6530 1.0000 (I=0.00) 1 200
MI (fatal and non fatal) RR=2.00 [0.07;58.95] 0.6880 1.0000 (I=0.00) 1 200
target-vessel revascularization RR=0.24 [0.12;0.50] 0.0000 1.0000 (I=0.00) 1 200
228 CHAPTER 25. DETAILS FOR COMPARISON VERSUS BALLON ANGIOPLASTY
Figure 25.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus ballon angioplasty
ISAR-DESIRE (PES vs PTCA)1/100 3/100 0.33 [0.04;3.15]
Global p ass= 0.3377 0.33 [0.04;3.15]
Sirolimus eluting stent versus ballon angioplasty
ISAR-DESIRE (SES vs PTCA)2/100 3/100 0.67 [0.11;3.90]
Global p ass= 0.6530 0.67 [0.11;3.90]
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 25.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus ballon angioplasty
ISAR-DESIRE (PES vs PTCA)2/100 0/100 4.00 [0.18;87.61]
Global p ass= 0.3787 4.00 [0.18;87.61]
Sirolimus eluting stent versus ballon angioplasty
ISAR-DESIRE (SES vs PTCA)1/100 0/100 2.00 [0.07;58.95]
Global p ass= 0.6880 2.00 [0.07;58.95]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 229
Figure 25.3: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus ballon angioplasty
ISAR-DESIRE (PES vs PTCA)19/100 33/100 0.58 [0.35;0.94]
Global p ass= 0.0278 0.58 [0.35;0.94]
Sirolimus eluting stent versus ballon angioplasty
ISAR-DESIRE (SES vs PTCA)8/100 33/100 0.24 [0.12;0.50]
Global p ass= 0.0000 0.24 [0.12;0.50]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, Schhlen H, Schmitt C, DirschingerJ, Schmig A. Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention ofrecurrences in patients with coronary in-stent restenosis: a randomized controlled trial.. JAMA 2005;293:165-71 [PMID=15644543]
[2] Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, Schhlen H, Schmitt C, DirschingerJ, Schmig A. Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention ofrecurrences in patients with coronary in-stent restenosis: a randomized controlled trial.. JAMA 2005;293:165-71 [PMID=15644543]
230 CHAPTER 26. DETAILS FOR COMPARISON VERSUS BRACHYTHERAPY
26 Detailed results for comparison versus
brachytherapy in in-stent restenosis
26.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus brachytherapyA total of 2 RCTs which randomized 780 patients were identified: 1 trial compared pa-
clitaxel eluting balloon with brachytherapy and 1 trial compared sirolimus eluting stent withbrachytherapy (see 26.1 page 231).
The average study size was 390 patients per arm (range 125 to 259 per arm). The first studywas published in 2006, and the last study was published in 2007.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on targetlesion revascularisation ; 1 trials reported data on MI (fatal and non fatal); 1 trials reporteddata on MACE; 1 trials reported data on CABG; 1 trials reported data on All cause death; and1 trials reported data on Stent thrombosis (any, end of follow up).
Following table 26.1 (page 231) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus brachytherapy.
26.1. AVAILABLE RCTS 231
Table
26.1
:M
ain
study
char
acte
rist
ics
-in
-ste
nt
rest
enos
is-
com
par
ison
vers
us
bra
chyth
erapy
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Paclita
xelelu
ting
balloon
vers
us
bra
chyth
era
py
TA
XU
SV
ISR
,2006
[1]
n=
195
vs.
201
pati
ents
wit
hre
sten
oti
cle
sions
aft
erpri
or
sten
tim
pla
nta
tion
innati
ve
coro
nary
art
erie
s
TA
XU
SE
xpre
ss2
vs.
angio
pla
sty
follow
edby
vasc
ula
rbra
chyth
erapy
wit
ha
bet
aso
urc
e
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:Is
chem
ia-d
riven
TV
Rat
9m
onth
s37
centr
es,
Nort
hA
mer
ica
Sirolim
us
elu
ting
stentvers
us
bra
chyth
era
py
SIS
R,
2007
[2,
3]
n=
259
vs.
125
rest
enosi
sw
ithin
abare
met
al
sten
tSir
olim
us-
eluti
ng
sten
tsvs.
bra
chyth
erapy
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:ta
rget
ves
sel
failure
26
centr
es,
US
and
Canadia
n
232 CHAPTER 26. DETAILS FOR COMPARISON VERSUS BRACHYTHERAPY
26.2 Meta-analysis results
The results are detailed in table 26.2 (page 232). This table is followed by the Forest’s plotcorresponding to each endpoint.
Paclitaxel eluting balloon versus brachytherapy
No data were presented in the 1 trial identified
Sirolimus eluting stent versus brachytherapy
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andbrachytherapy, with a RR of 0.48 (95%CI 0.01 to 24.18, p=0.7153) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 6.76 (95% CI 0.39 to 118.12, p=0.1906).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of0.52 (95% CI 0.31 to 0.87, p=0.0131).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target-vessel revascularization, with a RR of 0.50 (95% CI 0.31 to 0.81, p=0.0050).
The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target lesion revascularisation , with a RR of 0.44 (95% CI 0.26 to 0.76, p=0.0030).
The single study eligible for this comparison provided data on CABG. The analysis detecteda statistically significant difference in favor of sirolimus eluting stent in CABG, with a RR of0.08 (95% CI 0.01 to 0.66, p=0.0190).
Table 26.2: Results details - in-stent restenosis - comparison versus brachytherapy
Comparison Endpoint Effect 95% CI p ass hom k n
Paclitaxel eluting balloon versus brachytherapy
No data were presented in the trial identified
Sirolimus eluting stent versus brachytherapy
All cause death RR=0.48 [0.01;24.18] 0.7153 1.0000 (I=0.00) 1 384
MI (fatal and non fatal) RR=6.76 [0.39;118.12] 0.1906 1.0000 (I=0.00) 1 384
MACE RR=0.52 [0.31;0.87] 0.0131 1.0000 (I=0.00) 1 384
target-vessel revascularization RR=0.50 [0.31;0.81] 0.0050 1.0000 (I=0.00) 1 384
target lesion revascularisation RR=0.44 [0.26;0.76] 0.0030 1.0000 (I=1.00) 1 384
CABG RR=0.08 [0.01;0.66] 0.0190 1.0000 (I=0.00) 1 384
Stent thrombosis (any, end offollow up)
RR=1.93 [0.09;42.50] 0.6767 1.0000 (I=0.00) 1 384
26.2. META-ANALYSIS RESULTS 233
Figure 26.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus brachytherapy
SISR,2007 0/259 0/125 0.48 [0.01;24.18]
Global p ass= 0.7153 0.48 [0.01;24.18]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 26.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus brachytherapy
SISR,2007 7/259 0/125 6.76 [0.39;118.12]
Global p ass= 0.1906 6.76 [0.39;118.12]
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 26.3: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus brachytherapy
SISR,2007 26/259 24/125 0.52 [0.31;0.87]
Global p ass= 0.0131 0.52 [0.31;0.87]
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
234 CHAPTER 26. DETAILS FOR COMPARISON VERSUS BRACHYTHERAPY
Figure 26.4: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus brachytherapy
SISR,2007 28/259 27/125 0.50 [0.31;0.81]
Global p ass= 0.0050 0.50 [0.31;0.81]
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 26.5: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus brachytherapy
SISR,2007 22/259 24/125 0.44 [0.26;0.76]
Global p ass= 0.0030 0.44 [0.26;0.76]
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 26.6: Forest’s plot for CABG
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus brachytherapy
SISR,2007 1/259 6/125 0.08 [0.01;0.66]
Global p ass= 0.0190 0.08 [0.01;0.66]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 235
Figure 26.7: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus brachytherapy
SISR,2007 2/259 0/125 1.93 [0.09;42.50]
Global p ass= 0.6767 1.93 [0.09;42.50]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Stone GW, Ellis SG, O’Shaughnessy CD, Martin SL, Satler L, McGarry T, Turco MA, Kereiakes DJ, KelleyL, Popma JJ, Russell ME. Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis withinbare-metal stents: the TAXUS V ISR randomized trial.. JAMA 2006 Mar 15;295:1253-63 [PMID=16531618]
[2] Reynolds MR, Pinto DS, Shi C, Walczak J, Berezin R, Holmes DR, Cohen DJ, . Cost-effectiveness ofsirolimus-eluting stents compared with vascular brachytherapy for the treatment of in-stent restenosis.. AmHeart J 2007;154:1221-7. [PMID=18035097]
[3] Holmes DR Jr, Teirstein P, Satler L, Sketch M, O’Malley J, Popma JJ, Kuntz RE, Fitzgerald PJ, Wang H,Caramanica E, Cohen SA. Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis withinbare-metal stents: the SISR randomized trial.. JAMA 2006;295:1264-73 [PMID=16531619]
236CHAPTER 27. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
27 Detailed results for comparison versus paclitaxel
eluting stent in in-stent restenosis
27.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent
Only one trial which randomized 200 patients was identified: all compared sirolimus elutingstent with paclitaxel eluting stent (see 27.1 page 237).
The average study size was 200 patients per arm (range 100 to 100 per arm). The first studywas published in 2005, and the last study was published in 2005.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on MI(fatal and non fatal); 1 trials reported data on All cause death; 1 trials reported data on Stentthrombosis (any, end of follow up); and 1 trials reported data on 4y stent thrombosis (ARC).
Following table 27.1 (page 237) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus paclitaxel eluting stent.
27.1. AVAILABLE RCTS 237
Table
27.1
:M
ain
study
char
act
eris
tics
-in
-ste
nt
rest
enos
is-
com
par
ison
vers
us
pacl
itaxel
eluti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
ISA
R-D
ESIR
E(S
ES
vs
PE
S),
2005
[1]
n=
100
vs.
100
In-s
tent
rest
enosi
s.A
Pand/or
posi
tive
test
,pre
vio
usl
yst
ente
d,
no
AM
IC
ypher
vs.
Taxus
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s2
centr
es,
ger
many
238CHAPTER 27. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
27.2 Meta-analysis results
The results are detailed in table 27.2 (page 238). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus paclitaxel eluting stent
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andpaclitaxel eluting stent, with a RR of 2.00 (95%CI 0.18 to 21.71, p=0.5688) in favour of paclitaxeleluting stent. In other words, all cause death was slightly lower in the paclitaxel eluting stentgroup , but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 0.50 (95% CI 0.05 to 5.43, p=0.5688).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target-vessel revascularization, with a RR of 0.42 (95% CI 0.19 to 0.92, p=0.0294).
Table 27.2: Results details - in-stent restenosis - comparison versus paclitaxel eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=2.00 [0.18;21.71] 0.5688 1.0000 (I=0.00) 1 200
MI (fatal and non fatal) RR=0.50 [0.05;5.43] 0.5688 1.0000 (I=0.00) 1 200
target-vessel revascularization RR=0.42 [0.19;0.92] 0.0294 1.0000 (I=0.00) 1 200
Stent thrombosis (any, end offollow up)
RR=0.25 [0.01;5.48] 0.3787 1.0000 (I=0.00) 1 200
4y stent thrombosis (ARC) RR=0.25 [0.01;5.48] 0.3787 1.0000 (I=0.00) 1 200
Figure 27.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-DESIRE (SES vs PES),2/100 1/100 2.00 [0.18;21.71]
Global p ass= 0.5688 2.00 [0.18;21.71]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
27.2. META-ANALYSIS RESULTS 239
Figure 27.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-DESIRE (SES vs PES),1/100 2/100 0.50 [0.05;5.43]
Global p ass= 0.5688 0.50 [0.05;5.43]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 27.3: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-DESIRE (SES vs PES),8/100 19/100 0.42 [0.19;0.92]
Global p ass= 0.0294 0.42 [0.19;0.92]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 27.4: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-DESIRE (SES vs PES),0/100 2/100 0.25 [0.01;5.48]
Global p ass= 0.3787 0.25 [0.01;5.48]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
240 REFERENCES
Figure 27.5: Forest’s plot for 4y stent thrombosis (ARC)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
ISAR-DESIRE (SES vs PES),0/100 2/100 0.25 [0.01;5.48]
Global p ass= 0.3787 0.25 [0.01;5.48]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, Schhlen H, Schmitt C, DirschingerJ, Schmig A. Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention ofrecurrences in patients with coronary in-stent restenosis: a randomized controlled trial.. JAMA 2005;293:165-71 [PMID=15644543]
REFERENCES 241
28 Ongoing studies of in-stent restenosis
28.1 List of ongoing trials
No ongoing trial was identified. still ongoing at the date of this report. A list of these ongoingstudies with a brief description is given table 28.1.
Table 28.1: Ongoing studies for in-stent restenosis
Study Description
References
242 REFERENCES
Part VII
Bypass graft lesions
243
244
245
29 Overview of available evidence for bypass graft
lesions
Only one trial which randomized 75 patients was identified. (see tables 29.1 to 29.1 )In all, 1 report concerned comparison versus bare-metal stent.The detailed descriptions of trials and meta-analysis results is given in section 30 (page 251)
for comparison versus bare-metal stent.The average study size was 75 patients per arm (range 37 to 38 per arm). The first study
was published in 2006, and the last study was published in 2006.All trials were open-label in design. All included studies were reported in English language.
We did not found any unpublished trial.
246CHAPTER 29. OVERVIEW OF AVAILABLE EVIDENCE FOR BYPASS GRAFT LESIONS
Table
29.1
:M
ain
study
char
acte
rist
ics
-bypas
sgr
aft
lesi
ons
-co
mpar
ison
ver
sus
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
RR
ISC
,2006
[1,
2]
Cypher
vs.
BX
-Vel
oci
ty38
vs.
37
op
enP
ara
llel
gro
ups
Late
lum
enlo
ssB
elgiu
m,
The
net
her
lands
29.2. COMPARISON VERSUS BARE-METAL STENT - SUMMARY OF RESULTS 247
29.1 Main results for bypass graft lesions
The meta-analysis of the available trials provide the results listed in tables 29.2 to 29.2 (page247) and in the following graphs.
29.2 comparison versus bare-metal stent - summary of results
Sirolimus eluting stent was superior to bare-metal stent in terms of target-vessel revas-cularization (RR=0.19, 95% CI 0.05 to 0.83, p=0.0269, 1 trial) .But sirolimus eluting stentincreased the risk of 2 yr Death (all cause) (RR=21.42, 95% CI 1.31 to 351.48, p=0.0318, 1trial) .However, no significant difference was found on all cause death (RR=1.95, 95% CI 0.07 to56.32, p=0.6978, 1 trial) , MI (fatal and non fatal) (RR=2.92, 95% CI 0.32 to 26.83, p=0.3434,1 trial) , MACE (RR=0.53, 95% CI 0.22 to 1.29, p=0.1614, 1 trial) , 2 yr MACE (RR=1.43,95% CI 0.89 to 2.30, p=0.1416, 1 trial) , 2 yr TLR (RR=2.27, 95% CI 0.64 to 8.13, p=0.2070,1 trial) and target lesion revascularisation (RR=0.24, 95% CI 0.06 to 1.07, p=0.0617, 1 trial) .
Table 29.2: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus bare-metal stent
All cause death RR=1.95 0.07;56.32 0.6978 1.0000 (0.00) 1 75
2 yr Death (all cause) RR=21.42 1.31;351.48 0.0318 1.0000 (0.00) 1 75
MI (fatal and non fatal) RR=2.92 0.32;26.83 0.3434 1.0000 (0.00) 1 75
MACE RR=0.53 0.22;1.29 0.1614 1.0000 (0.00) 1 75
2 yr MACE RR=1.43 0.89;2.30 0.1416 1.0000 (0.00) 1 75
target-vessel revascularization RR=0.19 0.05;0.83 0.0269 1.0000 (1.00) 1 75
2 yr TLR RR=2.27 0.64;8.13 0.2070 1.0000 (0.00) 1 75
target lesion revascularisation RR=0.24 0.06;1.07 0.0617 1.0000 (0.00) 1 75
Figure 29.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
1.95 [0.07;56.32] .70 1 75 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
248CHAPTER 29. OVERVIEW OF AVAILABLE EVIDENCE FOR BYPASS GRAFT LESIONS
Figure 29.2: Forest’s plot for 2 yr Death (all cause)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
21.42 [1.31;351.48] .03 1 75 1.00 0.00
1.0 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 29.3: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
2.92 [0.32;26.83] .34 1 75 1.00 0.00
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 29.4: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.53 [0.22;1.29] .16 1 75 1.00 0.00
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
29.2. COMPARISON VERSUS BARE-METAL STENT - SUMMARY OF RESULTS 249
Figure 29.5: Forest’s plot for 2 yr MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
1.43 [0.89;2.30] .14 1 75 1.00 0.00
1.00.8 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 29.6: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.19 [0.05;0.83] .03 1 75 1.00 1.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 29.7: Forest’s plot for 2 yr TLR
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
2.27 [0.64;8.13] .21 1 75 1.00 0.00
1.00.5 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
250CHAPTER 29. OVERVIEW OF AVAILABLE EVIDENCE FOR BYPASS GRAFT LESIONS
Figure 29.8: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.24 [0.06;1.07] .06 1 75 1.00 0.00
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
251
30 Detailed results for comparison versus bare-metal
stent in bypass graft lesions
30.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
Only one trial which randomized 75 patients was identified: all compared sirolimus elutingstent with bare-metal stent (see 30.1 page 252).
The average study size was 75 patients per arm (range 37 to 38 per arm). The first studywas published in 2006, and the last study was published in 2006.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on targetlesion revascularisation ; 1 trials reported data on MI (fatal and non fatal); 1 trials reporteddata on MACE; 1 trials reported data on All cause death; 1 trials reported data on 2 yr TLR ;1 trials reported data on 2 yr MACE ; and 1 trials reported data on 2 yr Death (all cause) .
Following table 30.1 (page 252) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus bare-metal stent.
252 CHAPTER 30. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Table
30.1
:M
ain
study
chara
cter
isti
cs-
bypas
sgr
aft
lesi
ons
-co
mpari
son
ver
sus
bare
-met
alst
ent
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
RR
ISC
,2006
[1,
2]
n=
38
vs.
37
Sta
ble
or
unst
able
AP
,w
ith
pre
vio
us
coro
nary
art
ery
bypass
surg
ery
and
deg
ener
ate
dvei
ngra
fts
Cypher
vs.
BX
-Vel
oci
tyop
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:L
ate
lum
enlo
ss2
centr
es,
Bel
giu
m,
The
net
her
lands
30.2. META-ANALYSIS RESULTS 253
30.2 Meta-analysis results
The results are detailed in table 30.2 (page 253). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andbare-metal stent, with a RR of 1.95 (95%CI 0.07 to 56.32, p=0.6978) in favour of bare-metalstent. In other words, all cause death was slightly lower in the bare-metal stent group , but thiswas not statistically significant.
The single study eligible for this comparison provided data on 2 yr Death (all cause) .The analysis detected a statistically significant difference in favor of bare-metal stent in 2 yrDeath (all cause) , with a RR of 21.42 (95% CI 1.31 to 351.48, p=0.0318).
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 2.92 (95% CI 0.32 to 26.83, p=0.3434).
The single study eligible for this comparison provided data on MACE. No statisticallysignificant difference between the groups was found in MACE, with a RR of 0.53 (95% CI 0.22to 1.29, p=0.1614).
The single study eligible for this comparison provided data on 2 yr MACE . No statisticallysignificant difference between the groups was found in 2 yr MACE , with a RR of 1.43 (95% CI0.89 to 2.30, p=0.1416).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target-vessel revascularization, with a RR of 0.19 (95% CI 0.05 to 0.83, p=0.0269).
The single study eligible for this comparison provided data on 2 yr TLR . No statisticallysignificant difference between the groups was found in 2 yr TLR , with a RR of 2.27 (95% CI0.64 to 8.13, p=0.2070).
The single study eligible for this comparison provided data on target lesion revascular-isation . No statistically significant difference between the groups was found in target lesionrevascularisation , with a RR of 0.24 (95% CI 0.06 to 1.07, p=0.0617).
Table 30.2: Results details - bypass graft lesions - comparison versus bare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus bare-metal stent
All cause death RR=1.95 [0.07;56.32] 0.6978 1.0000 (I=0.00) 1 75
2 yr Death (all cause) RR=21.42 [1.31;351.48] 0.0318 1.0000 (I=0.00) 1 75
MI (fatal and non fatal) RR=2.92 [0.32;26.83] 0.3434 1.0000 (I=0.00) 1 75
MACE RR=0.53 [0.22;1.29] 0.1614 1.0000 (I=0.00) 1 75
2 yr MACE RR=1.43 [0.89;2.30] 0.1416 1.0000 (I=0.00) 1 75
target-vessel revascularization RR=0.19 [0.05;0.83] 0.0269 1.0000 (I=1.00) 1 75
2 yr TLR RR=2.27 [0.64;8.13] 0.2070 1.0000 (I=0.00) 1 75
target lesion revascularisation RR=0.24 [0.06;1.07] 0.0617 1.0000 (I=0.00) 1 75
254 CHAPTER 30. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 30.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 1/38 0/37 1.95 [0.07;56.32]
Global p ass= 0.6978 1.95 [0.07;56.32]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 30.2: Forest’s plot for 2 yr Death (all cause)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 11/38 0/37 21.42 [1.31;351.48]
Global p ass= 0.0318 21.42 [1.31;351.48]
1.0 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 30.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 3/38 1/37 2.92 [0.32;26.83]
Global p ass= 0.3434 2.92 [0.32;26.83]
1.00.2 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
30.2. META-ANALYSIS RESULTS 255
Figure 30.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 6/38 11/37 0.53 [0.22;1.29]
Global p ass= 0.1614 0.53 [0.22;1.29]
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 30.5: Forest’s plot for 2 yr MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 22/38 15/37 1.43 [0.89;2.30]
Global p ass= 0.1416 1.43 [0.89;2.30]
1.00.8 2.0 4.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 30.6: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 2/38 10/37 0.19 [0.05;0.83]
Global p ass= 0.0269 0.19 [0.05;0.83]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
256 REFERENCES
Figure 30.7: Forest’s plot for 2 yr TLR
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 7/38 3/37 2.27 [0.64;8.13]
Global p ass= 0.2070 2.27 [0.64;8.13]
1.00.5 5.0 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 30.8: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
RRISC,2006 2/38 8/37 0.24 [0.06;1.07]
Global p ass= 0.0617 0.24 [0.06;1.07]
1.00.1 2.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Vermeersch P, Agostoni P, Verheye S, Van den Heuvel P, Convens C, Van den Branden F, Van LangenhoveG. Increased late mortality after sirolimus-eluting stents versus bare-metal stents in diseased saphenousvein grafts: results from the randomized DELAYED RRISC Trial.. J Am Coll Cardiol 2007 Jul 17;50:261-7[PMID=17631219]
[2] Vermeersch P, Agostoni P, Verheye S, Van den Heuvel P, Convens C, Bruining N, Van den Branden F, VanLangenhove G. Randomized double-blind comparison of sirolimus-eluting stent versus bare-metal stent im-plantation in diseased saphenous vein grafts: six-month angiographic, intravascular ultrasound, and clinicalfollow-up of the RRISC Trial.. J Am Coll Cardiol 2006 Dec 19;48:2423-31 [PMID=17174178]
REFERENCES 257
31 Ongoing studies of bypass graft lesions
31.1 List of ongoing trials
A total of 3 studies were still ongoing at the date of this report. A list of these ongoing studieswith a brief description is given table 31.1.
Table 31.1: Ongoing studies for bypass graft lesions
Study Description
ISAR-CABG (0)[] NCT00611910
DES vs. BMS
Bypass Graft Lesions
BASKET-SAVAGE (0)[] NCT00595647
Taxus vs. Libert
percutaneous coronary interventions of saphenous vein grafts
VELETI (0)[] NCT00289835
TAXUS vs. standard medical treatment
Moderate Vein Graft Lesions
References
258 REFERENCES
Part VIII
Unprotected left main coronaryartery stenosis
259
260
261
32 Overview of available evidence for unprotected
left main coronary artery stenosis
Only one trial which randomized 103 patients was identified. (see tables 32.1 to 32.1 )In all, 1 report concerned comparison versus bare-metal stent.The detailed descriptions of trials and meta-analysis results is given in section 33 (page 266)
for comparison versus bare-metal stent.The average study size was 103 patients per arm (range 50 to 53 per arm). The first study
was published in 2007, and the last study was published in 2007.All trials were open-label in design. All included studies were reported in English language.
We did not found any unpublished trial.
262CHAPTER 32. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPROTECTED LEFT MAIN CORONARY ARTERY STENOSIS
Table
32.1
:M
ain
study
char
act
eris
tics
-unpro
tect
edle
ftm
ain
coro
nar
yar
tery
sten
osis
-co
mpari
son
vers
us
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
Erg
lis,
2007
[1]
IVU
S-g
uid
edpacl
itaxel
-elu
ting
sten
t(T
axus
Expre
ss)
aft
erle
sion
pre
-tre
atm
ent
wit
hcu
ttin
gballoon
vs.
IVU
S-g
uid
edbare
-met
al
(Expre
ssor
Lib
erte
)aft
erle
sion
pre
-tre
atm
ent
wit
hcu
ttin
gballoon
53
vs.
50
op
enP
ara
llel
gro
ups
NA
NA
32.2. COMPARISON VERSUS BARE-METAL STENT - SUMMARY OF RESULTS 263
32.1 Main results for unprotected left main coronary arterystenosis
The meta-analysis of the available trials provide the results listed in tables 32.2 to 32.2 (page263) and in the following graphs.
32.2 comparison versus bare-metal stent - summary of results
Paclitaxel eluting stent was superior to bare-metal stent in terms of MACE (RR=0.44,95% CI 0.20 to 0.99, p=0.0470, 1 trial) and target lesion revascularisation (RR=0.12, 95% CI0.02 to 0.91, p=0.0402, 1 trial) .However, no significant difference was found on all cause death(RR=0.94, 95% CI 0.06 to 14.68, p=0.9668, 1 trial) , cardiac death (RR=1.89, 95% CI 0.06 to55.02, p=0.7122, 1 trial) and MI (fatal and non fatal) (RR=0.67, 95% CI 0.23 to 1.99, p=0.4740,1 trial) .
Table 32.2: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=0.94 0.06;14.68 0.9668 1.0000 (0.00) 1 103
cardiac death RR=1.89 0.06;55.02 0.7122 1.0000 (0.00) 1 103
MI (fatal and non fatal) RR=0.67 0.23;1.99 0.4740 1.0000 (0.00) 1 103
MACE RR=0.44 0.20;0.99 0.0470 1.0000 (0.00) 1 103
target lesion revascularisation RR=0.12 0.02;0.91 0.0402 1.0000 (0.00) 1 103
Figure 32.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.94 [0.06;14.68] .97 1 103 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
264CHAPTER 32. OVERVIEW OF AVAILABLE EVIDENCE FOR UNPROTECTED LEFT MAIN CORONARY ARTERY STENOSIS
Figure 32.2: Forest’s plot for cardiac death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
1.89 [0.06;55.02] .71 1 103 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 32.3: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.67 [0.23;1.99] .47 1 103 1.00 0.00
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 32.4: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.44 [0.20;0.99] .05 1 103 1.00 0.00
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.7 0.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
32.2. COMPARISON VERSUS BARE-METAL STENT - SUMMARY OF RESULTS 265
Figure 32.5: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Paclitaxel eluting stent versus bare-metalstent
0.12 [0.02;0.91] .04 1 103 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
266 CHAPTER 33. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
33 Detailed results for comparison versus bare-metal
stent in unprotected left main coronary artery
stenosis
33.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
Only one trial which randomized 103 patients was identified: all compared paclitaxel elutingstent with bare-metal stent (see 33.1 page 267).
The average study size was 103 patients per arm (range 50 to 53 per arm). The first studywas published in 2007, and the last study was published in 2007.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI(fatal and non fatal); 1 trials reported data on MACE; 1 trials reported data on cardiac death;and 1 trials reported data on All cause death.
Following table 33.1 (page 267) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus bare-metal stent.
33.1. AVAILABLE RCTS 267
Table
33.1
:M
ain
study
chara
cter
isti
cs-
unpro
tect
edle
ftm
ain
coro
nar
yar
tery
sten
osi
s-
com
pari
son
vers
us
bare
-met
alst
ent
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Paclita
xelelu
ting
stentvers
us
bare
-meta
lst
ent
Erg
lis,
2007
[1]
n=
53
vs.
50
per
cuta
neo
us
coro
nary
inte
rven
tion
for
unpro
tect
edle
ftm
ain
art
ery
sten
osi
sIV
US-g
uid
edpacl
itaxel
-elu
ting
sten
t(T
axus
Expre
ss)
aft
erle
sion
pre
-tre
atm
ent
wit
hcu
ttin
gballoon
vs.
IVU
S-g
uid
edbare
-met
al
(Expre
ssor
Lib
erte
)aft
erle
sion
pre
-tre
atm
ent
wit
hcu
ttin
gballoon
No
of
sten
tp
erle
sions:
1.0
2
op
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:N
A,
NA
268 CHAPTER 33. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
33.2 Meta-analysis results
The results are detailed in table 33.2 (page 268). This table is followed by the Forest’s plotcorresponding to each endpoint.
Paclitaxel eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between paclitaxel eluting stent andbare-metal stent, with a RR of 0.94 (95%CI 0.06 to 14.68, p=0.9668) in favour of paclitaxeleluting stent. In other words, all cause death was slightly lower in the paclitaxel eluting stentgroup , but this was not statistically significant.
The single study eligible for this comparison provided data on cardiac death. No statis-tically significant difference between the groups was found in cardiac death, with a RR of 1.89(95% CI 0.06 to 55.02, p=0.7122).
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 0.67 (95% CI 0.23 to 1.99, p=0.4740).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of paclitaxel eluting stent in MACE, with a RR of0.44 (95% CI 0.20 to 0.99, p=0.0470).
The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of paclitaxel elutingstent in target lesion revascularisation , with a RR of 0.12 (95% CI 0.02 to 0.91, p=0.0402).
Table 33.2: Results details - unprotected left main coronary artery stenosis - comparison versusbare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Paclitaxel eluting stent versus bare-metal stent
All cause death RR=0.94 [0.06;14.68] 0.9668 1.0000 (I=0.00) 1 103
cardiac death RR=1.89 [0.06;55.02] 0.7122 1.0000 (I=0.00) 1 103
MI (fatal and non fatal) RR=0.67 [0.23;1.99] 0.4740 1.0000 (I=0.00) 1 103
MACE RR=0.44 [0.20;0.99] 0.0470 1.0000 (I=0.00) 1 103
target lesion revascularisation RR=0.12 [0.02;0.91] 0.0402 1.0000 (I=0.00) 1 103
Figure 33.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
Erglis,2007 1/53 1/50 0.94 [0.06;14.68]
Global p ass= 0.9668 0.94 [0.06;14.68]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
33.2. META-ANALYSIS RESULTS 269
Figure 33.2: Forest’s plot for cardiac death
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
Erglis,2007 1/53 0/50 1.89 [0.06;55.02]
Global p ass= 0.7122 1.89 [0.06;55.02]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 33.3: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
Erglis,2007 5/53 7/50 0.67 [0.23;1.99]
Global p ass= 0.4740 0.67 [0.23;1.99]
1.00.2 1.0 2.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 33.4: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
Erglis,2007 7/53 15/50 0.44 [0.20;0.99]
Global p ass= 0.0470 0.44 [0.20;0.99]
1.00.90.80.70.60.50.40.30.20.20.10.2 0.3 0.4 0.5 0.6 0.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
270 REFERENCES
Figure 33.5: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Paclitaxel eluting stent versus bare-metal stent
Erglis,2007 1/53 8/50 0.12 [0.02;0.91]
Global p ass= 0.0402 0.12 [0.02;0.91]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Erglis A, Narbute I, Kumsars I, Jegere S, Mintale I, Zakke I, Strazdins U, Saltups A. A randomized com-parison of paclitaxel-eluting stents versus bare-metal stents for treatment of unprotected left main coronaryartery stenosis.. J Am Coll Cardiol 2007;50:491-7 [PMID=17678730]
REFERENCES 271
34 Ongoing studies of unprotected left main
coronary artery stenosis
34.1 List of ongoing trials
A total of 3 studies were still ongoing at the date of this report. A list of these ongoing studieswith a brief description is given table 34.1.
Table 34.1: Ongoing studies for unprotected left main coronary artery stenosis
Study Description
ISAR-LEFT-MAIN (0)[] NCT00133237
Sirolimus-eluting stent vs. Paclitaxel-eluting stent
Unprotected Left Main Coronary Artery Disease
LEFT-MAIN-2 (0)[] NCT00598637
Xience vs. Endeavor Resolute
unprotected left main coronary artery disease
Leipzig (0)[] NCT00176397
PCI With DES vs. CABG
left main coronary stenosis
References
272 REFERENCES
Part IX
Total occlusion
273
274
275
35 Overview of available evidence for total occlusion
Only one trial which randomized 200 patients was identified. (see tables 35.1 to 35.1 )In all, 1 report concerned comparison versus bare-metal stent.The detailed descriptions of trials and meta-analysis results is given in section 36 (page 280)
for comparison versus bare-metal stent.The average study size was 200 patients per arm (range 100 to 100 per arm). The first study
was published in 2006, and the last study was published in 2006.Erreur ??? 0 et 0.All included studies were reported in English language. We did not found any unpublished
trial.
276 CHAPTER 35. OVERVIEW OF AVAILABLE EVIDENCE FOR TOTAL OCCLUSION
Table
35.1
:M
ain
study
char
acte
rist
ics
-to
talocc
lusi
on-
com
par
ison
vers
us
bare
-met
alst
ent
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
bare
-meta
lst
ent
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
PR
ISO
NII
,2006
[1]
Cypher
vs.
BxV
eloci
ty100
vs.
100
single
-blind
Para
llel
gro
ups
Bin
ary
rest
enosi
sB
elgiu
m
35.2. COMPARISON VERSUS BARE-METAL STENT - SUMMARY OF RESULTS 277
35.1 Main results for total occlusion
The meta-analysis of the available trials provide the results listed in tables 35.2 to 35.2 (page277) and in the following graphs.
35.2 comparison versus bare-metal stent - summary of results
Sirolimus eluting stent was superior to bare-metal stent in terms of MACE (RR=0.20,95% CI 0.07 to 0.56, p=0.0024, 1 trial) , target-vessel revascularization (RR=0.36, 95% CI 0.17to 0.78, p=0.0091, 1 trial) , target lesion revascularisation (RR=0.21, 95% CI 0.07 to 0.60,p=0.0034, 1 trial) and angiographic restenosis (RR=0.19, 95% CI 0.09 to 0.42, p=0.0000, 1trial) .However, no significant difference was found on all cause death (RR=1.00, 95% CI 0.02 to49.91, p=1.0000, 1 trial) and MI (fatal and non fatal) (RR=0.67, 95% CI 0.11 to 3.90, p=0.6530,1 trial) .
Table 35.2: Summary of all results for comparison versus bare-metal stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus bare-metal stent
All cause death RR=1.00 0.02;49.91 1.0000 1.0000 (0.00) 1 200
MI (fatal and non fatal) RR=0.67 0.11;3.90 0.6530 1.0000 (0.00) 1 200
MACE RR=0.20 0.07;0.56 0.0024 1.0000 (0.00) 1 200
target-vessel revascularization RR=0.36 0.17;0.78 0.0091 1.0000 (1.00) 1 200
target lesion revascularisation RR=0.21 0.07;0.60 0.0034 1.0000 (0.00) 1 200
Stent thrombosis (any, end offollow up)
RR=4.00 0.18;87.61 0.3787 1.0000 (0.00) 1 200
angiographic restenosis RR=0.19 0.09;0.42 0.0000 1.0000 (1.00) 1 200
Figure 35.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
1.00 [0.02;49.91] 1.00 1 200 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
278 CHAPTER 35. OVERVIEW OF AVAILABLE EVIDENCE FOR TOTAL OCCLUSION
Figure 35.2: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.67 [0.11;3.90] .65 1 200 1.00 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 35.3: Forest’s plot for MACE
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.20 [0.07;0.56] .00 1 200 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 35.4: Forest’s plot for target-vessel revascularization
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.36 [0.17;0.78] .01 1 200 1.00 1.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
35.2. COMPARISON VERSUS BARE-METAL STENT - SUMMARY OF RESULTS 279
Figure 35.5: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.21 [0.07;0.60] .00 1 200 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 35.6: Forest’s plot for stent thrombosis (any, end of follow up)
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
4.00 [0.18;87.61] .38 1 200 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 35.7: Forest’s plot for angiographic restenosis
RR [95%CI] p k n p het I2
comparison versus bare-metal stent
Sirolimus eluting stent versus bare-metalstent
0.19 [0.09;0.42] .00 1 200 1.00 1.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
280 CHAPTER 36. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
36 Detailed results for comparison versus bare-metal
stent in total occlusion
36.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus bare-metalstent
Only one trial which randomized 200 patients was identified: all compared sirolimus elutingstent with bare-metal stent (see 36.1 page 281).
The average study size was 200 patients per arm (range 100 to 100 per arm). The first studywas published in 2006, and the last study was published in 2006.
Erreur ??? 0 et 0.All included studies were reported in English language. We did not found any unpublished
trial.Target-vessel revascularization data was reported in 1 trials; 1 trials reported data on target
lesion revascularisation ; 1 trials reported data on MI (fatal and non fatal); 1 trials reporteddata on MACE; 1 trials reported data on angiographic restenosis ; 1 trials reported data on Allcause death; and 1 trials reported data on Stent thrombosis (any, end of follow up).
Following table 36.1 (page 281) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus bare-metal stent.
36.1. AVAILABLE RCTS 281
Table
36.1
:M
ain
study
char
acte
rist
ics
-to
talocc
lusi
on-
com
par
ison
vers
us
bare
-met
alst
ent
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Sirolim
us
elu
ting
stentvers
us
bare
-meta
lst
ent
PR
ISO
NII
,2006
[1]
n=
100
vs.
100
Chro
nic
tota
locc
lusi
on,
posi
tive
exer
cise
stre
sste
stC
ypher
vs.
BxV
eloci
tysi
ngle
-blind
Para
llel
gro
ups
Pri
mary
endp
oin
t:B
inary
rest
enosi
s2
centr
es,
Bel
giu
m
282 CHAPTER 36. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
36.2 Meta-analysis results
The results are detailed in table 36.2 (page 282). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus bare-metal stent
The single study eligible for this comparison provided data on all cause death. There wasno statistically significant difference in all cause death between sirolimus eluting stent and bare-metal stent, with a RR of 1.00 (95%CI 0.02 to 49.91, p=1.0000) in favour of sirolimus elutingstent. In other words, all cause death was slightly lower in the sirolimus eluting stent group ,but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 0.67 (95% CI 0.11 to 3.90, p=0.6530).
The single study eligible for this comparison provided data on MACE. The analysis detecteda statistically significant difference in favor of sirolimus eluting stent in MACE, with a RR of0.20 (95% CI 0.07 to 0.56, p=0.0024).
The single study eligible for this comparison provided data on target-vessel revascular-ization. The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target-vessel revascularization, with a RR of 0.36 (95% CI 0.17 to 0.78, p=0.0091).
The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target lesion revascularisation , with a RR of 0.21 (95% CI 0.07 to 0.60, p=0.0034).
The single study eligible for this comparison provided data on angiographic restenosis .The analysis detected a statistically significant difference in favor of sirolimus eluting stent inangiographic restenosis , with a RR of 0.19 (95% CI 0.09 to 0.42, p=0.0000).
Table 36.2: Results details - total occlusion - comparison versus bare-metal stent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus bare-metal stent
All cause death RR=1.00 [0.02;49.91] 1.0000 1.0000 (I=0.00) 1 200
MI (fatal and non fatal) RR=0.67 [0.11;3.90] 0.6530 1.0000 (I=0.00) 1 200
MACE RR=0.20 [0.07;0.56] 0.0024 1.0000 (I=0.00) 1 200
target-vessel revascularization RR=0.36 [0.17;0.78] 0.0091 1.0000 (I=1.00) 1 200
target lesion revascularisation RR=0.21 [0.07;0.60] 0.0034 1.0000 (I=0.00) 1 200
Stent thrombosis (any, end offollow up)
RR=4.00 [0.18;87.61] 0.3787 1.0000 (I=0.00) 1 200
angiographic restenosis RR=0.19 [0.09;0.42] 0.0000 1.0000 (I=1.00) 1 200
36.2. META-ANALYSIS RESULTS 283
Figure 36.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
PRISON II,2006 0/100 0/100 1.00 [0.02;49.91]
Global p ass= 1.0000 1.00 [0.02;49.91]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 36.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
PRISON II,2006 2/100 3/100 0.67 [0.11;3.90]
Global p ass= 0.6530 0.67 [0.11;3.90]
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 36.3: Forest’s plot for MACE
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
PRISON II,2006 4/100 20/100 0.20 [0.07;0.56]
Global p ass= 0.0024 0.20 [0.07;0.56]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
284 CHAPTER 36. DETAILS FOR COMPARISON VERSUS BARE-METAL STENT
Figure 36.4: Forest’s plot for target-vessel revascularization
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
PRISON II,2006 8/100 22/100 0.36 [0.17;0.78]
Global p ass= 0.0091 0.36 [0.17;0.78]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 36.5: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
PRISON II,2006 4/100 19/100 0.21 [0.07;0.60]
Global p ass= 0.0034 0.21 [0.07;0.60]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 36.6: Forest’s plot for stent thrombosis (any, end of follow up)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
PRISON II,2006 2/100 0/100 4.00 [0.18;87.61]
Global p ass= 0.3787 4.00 [0.18;87.61]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
REFERENCES 285
Figure 36.7: Forest’s plot for angiographic restenosis
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus bare-metal stent
PRISON II,2006 7/100 36/100 0.19 [0.09;0.42]
Global p ass= 0.0000 0.19 [0.09;0.42]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Suttorp MJ, Laarman GJ, Rahel BM, Kelder JC, Bosschaert MA, Kiemeneij F, Ten Berg JM, Bal ET, Rens-ing BJ, Eefting FD, Mast EG. Primary Stenting of Totally Occluded Native Coronary Arteries II (PRISONII): a randomized comparison of bare metal stent implantation with sirolimus-eluting stent implantation forthe treatment of total coronary occlusions.. Circulation 2006;114:921-8 [PMID=16908768]
286 REFERENCES
REFERENCES 287
37 Ongoing studies of total occlusion
37.1 List of ongoing trials
A total of 2 studies were still ongoing at the date of this report. A list of these ongoing studieswith a brief description is given table 37.1.
Table 37.1: Ongoing studies for total occlusion
Study Description
PRISON III (2007)[1] NCT00428454
Endeavor vs. Cypher
patients with total coronary occlusions for at least 2 weeks with evi-dence of ischemia related to the occluded coronary artery
GISSOC II (0)[] NCT00220558
Cypher Select-TM Sirolimus Eluting Stent vs. SONIC-TM Bare MetalStent
Chronic Total Occlusion lesions
References
[1] Suttorp MJ, Laarman GJ. A randomized comparison of sirolimus-eluting stent implantation withzotarolimus-eluting stent implantation for the treatment of total coronary occlusions: rationale and de-sign of the PRImary Stenting of Occluded Native coronary arteries III (PRISON III) study.. Am Heart J2007 Sep;154:432-5 [PMID=17719285]
288 REFERENCES
Part X
Bifurcation
289
290
291
38 Overview of available evidence for bifurcation
Only one trial which randomized 205 patients was identified. (see tables 38.1 to 38.1 )In all, 1 report concerned comparison versus paclitaxel eluting stent.The detailed descriptions of trials and meta-analysis results is given in section 39 (page 295)
for comparison versus paclitaxel eluting stent.The average study size was 205 patients per arm (range 102 to 103 per arm). The first study
was published in 2007, and the last study was published in 2007.All trials were open-label in design. All included studies were reported in English language.
We did not found any unpublished trial.
292 CHAPTER 38. OVERVIEW OF AVAILABLE EVIDENCE FOR BIFURCATION
Table
38.1
:M
ain
study
char
acte
rist
ics
-bifurc
atio
n-
com
par
ison
ver
sus
pacl
itaxel
eluti
ng
sten
t
Tri
al
Com
pari
son
Eff
ecti
ves
Blindin
gD
esi
gn
Pri
mary
endp
oin
tL
ocalisa
tion
com
pari
son
vers
us
paclita
xel
elu
ting
stent
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Pan,
2007
[1]
SE
Svs.
PE
S103
vs.
102
op
enP
ara
llel
gro
ups
none
Spain
38.2. COMPARISON VERSUS PACLITAXEL ELUTING STENT - SUMMARY OF RESULTS293
38.1 Main results for bifurcation
The meta-analysis of the available trials provide the results listed in tables 38.2 to 38.2 (page293) and in the following graphs.
38.2 comparison versus paclitaxel eluting stent - summary ofresults
Sirolimus eluting stent was superior to paclitaxel eluting stent in terms of target lesionrevascularisation (RR=0.30, 95% CI 0.10 to 0.90, p=0.0321, 1 trial) .However, no significantdifference was found on all cause death (RR=0.66, 95% CI 0.11 to 3.87, p=0.6453, 1 trial) andMI (fatal and non fatal) (RR=0.99, 95% CI 0.14 to 6.90, p=0.9921, 1 trial) .
Table 38.2: Summary of all results for comparison versus paclitaxel eluting stent
Endpoint Effect 95% CI p ass p het (I2) k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.66 0.11;3.87 0.6453 1.0000 (0.00) 1 205
MI (fatal and non fatal) RR=0.99 0.14;6.90 0.9921 1.0000 (0.00) 1 205
target lesion revascularisation RR=0.30 0.10;0.90 0.0321 1.0000 (0.00) 1 205
Figure 38.1: Forest’s plot for all cause death
RR [95%CI] p k n p het I2
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.66 [0.11;3.87] .65 1 205 1.00 0.00
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
294 CHAPTER 38. OVERVIEW OF AVAILABLE EVIDENCE FOR BIFURCATION
Figure 38.2: Forest’s plot for MI (fatal and non fatal)
RR [95%CI] p k n p het I2
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.99 [0.14;6.90] .99 1 205 1.00 0.00
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
Figure 38.3: Forest’s plot for target lesion revascularisation
RR [95%CI] p k n p het I2
comparison versus paclitaxel eluting stent
Sirolimus eluting stent versus paclitaxeleluting stent
0.30 [0.10;0.90] .03 1 205 1.00 0.00
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
Results obtained with a fixed effect model except in case of heterogenity where a random model was used
RR: relative risk; 95% CI: 95% confidence interval; p: p-value of the association test; k: number of trials; n: total
number of patients involving in the pooled trials; p het: p-value of the hetereogenity test
295
39 Detailed results for comparison versus paclitaxel
eluting stent in bifurcation
39.1 Available RCTs
This section gives details for trials evaluating drug eluting stent comparison versus paclitaxeleluting stent
Only one trial which randomized 205 patients was identified: all compared sirolimus elutingstent with paclitaxel eluting stent (see 39.1 page 296).
The average study size was 205 patients per arm (range 102 to 103 per arm). The first studywas published in 2007, and the last study was published in 2007.
All trials were open-label in design. All included studies were reported in English language.We did not found any unpublished trial.
Target lesion revascularisation data was reported in 1 trials; 1 trials reported data on MI(fatal and non fatal); and 1 trials reported data on All cause death.
Following table 39.1 (page 296) summarized the main characteristics of the trials includingin this systematic review of RCTS of comparison versus paclitaxel eluting stent.
296CHAPTER 39. DETAILS FOR COMPARISON VERSUS PACLITAXEL ELUTING STENT
Table
39.1
:M
ain
study
chara
cter
isti
cs-
bifurc
atio
n-
com
par
ison
ver
sus
pac
lita
xel
eluti
ng
sten
t
Tri
al
Pati
ents
Tre
atm
ents
Desi
gn
Sirolim
us
elu
ting
stentvers
us
paclita
xelelu
ting
stent
Pan,
2007
[1]
n=
103
vs.
102
pati
ents
wit
hbif
urc
ati
on
lesi
ons
SE
Svs.
PE
Sop
enP
ara
llel
gro
ups
Pri
mary
endp
oin
t:none
2ce
ntr
es,
Spain
39.2. META-ANALYSIS RESULTS 297
39.2 Meta-analysis results
The results are detailed in table 39.2 (page 297). This table is followed by the Forest’s plotcorresponding to each endpoint.
Sirolimus eluting stent versus paclitaxel eluting stent
The single study eligible for this comparison provided data on all cause death. Therewas no statistically significant difference in all cause death between sirolimus eluting stent andpaclitaxel eluting stent, with a RR of 0.66 (95%CI 0.11 to 3.87, p=0.6453) in favour of sirolimuseluting stent. In other words, all cause death was slightly lower in the sirolimus eluting stentgroup , but this was not statistically significant.
The single study eligible for this comparison provided data on MI (fatal and non fatal).No statistically significant difference between the groups was found in MI (fatal and non fatal),with a RR of 0.99 (95% CI 0.14 to 6.90, p=0.9921).
The single study eligible for this comparison provided data on target lesion revasculari-sation . The analysis detected a statistically significant difference in favor of sirolimus elutingstent in target lesion revascularisation , with a RR of 0.30 (95% CI 0.10 to 0.90, p=0.0321).
Table 39.2: Results details - bifurcation - comparison versus paclitaxel eluting stent
Comparison Endpoint Effect 95% CI p ass hom k n
Sirolimus eluting stent versus paclitaxel eluting stent
All cause death RR=0.66 [0.11;3.87] 0.6453 1.0000 (I=0.00) 1 205
MI (fatal and non fatal) RR=0.99 [0.14;6.90] 0.9921 1.0000 (I=0.00) 1 205
target lesion revascularisation RR=0.30 [0.10;0.90] 0.0321 1.0000 (I=0.00) 1 205
Figure 39.1: Forest’s plot for all cause death
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Pan,2007 2/103 3/102 0.66 [0.11;3.87]
Global p ass= 0.6453 0.66 [0.11;3.87]
1.00.1 5.0Relative risk
treatment worsens outcometreatment improves outcome
298 REFERENCES
Figure 39.2: Forest’s plot for MI (fatal and non fatal)
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Pan,2007 2/103 2/102 0.99 [0.14;6.90]
Global p ass= 0.9921 0.99 [0.14;6.90]
1.00.1 10.0Relative risk
treatment worsens outcometreatment improves outcome
Figure 39.3: Forest’s plot for target lesion revascularisation
Trial studied T. control T. RR [95%CI]
Sirolimus eluting stent versus paclitaxel eluting stent
Pan,2007 4/103 13/102 0.30 [0.10;0.90]
Global p ass= 0.0321 0.30 [0.10;0.90]
1.00.90.80.70.60.50.40.30.20.10.10.1 0.2 0.3 0.4 0.50.60.70.80.91.0Relative risk
treatment worsens outcometreatment improves outcome
References
[1] Pan M, Surez de Lezo J, Medina A, Romero M, Delgado A, Segura J, Ojeda S, Mazuelos F, HernandezE, Melian F, Pavlovic D, Esteban F, Herrador J. Drug-eluting stents for the treatment of bifurcation le-sions: a randomized comparison between paclitaxel and sirolimus stents.. Am Heart J 2007 Jan;153:15.e1-7[PMID=17174630]
REFERENCES 299
40 Ongoing studies of bifurcation
40.1 List of ongoing trials
A total of 2 studies were still ongoing at the date of this report. A list of these ongoing studieswith a brief description is given table 40.1.
Table 40.1: Ongoing studies for bifurcation
Study Description
Nordic Bifurcation StentTechnique Study (0)[] NCT00292305
crush stenting vs. culotte stenting
bifurcation lesions
Nordic Bifurcation Study(0)[] NCT00376571
Strategy of Routine Stenting Both Main Vessel and Side Branch vs.Strategy of Routine Main Vessel Stenting and Optional Treatment ofSide Branch
bifurcation lesions
References
300 REFERENCES
Index
comparison versus ballon angioplasty, 225results table, 219Trials description, 216
comparison versus bare-metal stent, 29, 92, 129,160, 189, 251, 266, 280
results table, 15, 83, 120, 154, 181, 247,263, 277
Trials description, 10, 80, 118, 152, 178,246, 262, 276
comparison versus brachytherapy, 230results table, 220Trials description, 217
comparison versus CABG, 197results table, 182Trials description, 179
comparison versus paclitaxel eluting stent, 53,103, 140, 166, 202, 236, 295
results table, 17, 84, 121, 154, 182, 220, 293Trials description, 12, 81, 119, 153, 180,
218, 292comparison versus rapamycin eluting stent, 110
results table, 84Trials description, 82
comparison versus sirolimus eluting stent, 66results table, 17Trials description, 13
ACTION, 10, 30reference, 50
Acute myocardial infarction, 115available trials, 117excluded studies, 147main results, 120
ASPECT, 11, 32reference, 51
BASKET (vs paclitaxel), 12, 55reference, 65
BASKET-PROVE, 75reference, 76
BASKET-SAVAGE, 257Bifurcation, 289bifurcation
available trials, 291
excluded studies, 299main results, 293
Bypass graft lesions, 243bypass graft lesions
available trials, 245excluded studies, 257main results, 247
C-SIRIUS, 11, 33reference, 52
Cervinka, 180, 203reference, 208
COMBAT, 75CORPAL, 180, 203
reference, 209Costar II, 12, 54
reference, 64
DECODE, 80, 94reference, 102
DEDICATION, 118, 130reference, 139
DELIVER, 11, 32reference, 51
DESSERT, 80, 93reference, 102
Di Lorenzo et al., 119, 141reference, 146
DIABEDES IV, 113DIABETES, 80, 94
reference, 102Diabetic patients, 77
available trials, 79excluded studies, 113main results, 83
Daz de la Llera, 118, 130reference, 139
E-SIRIUS, 11, 33reference, 52
ELUTES, 11, 32reference, 51
ENDEAVOR II, 11, 34reference, 52
301
302 INDEX
ENDEAVOR III, 13, 67reference, 74
ENDEAVOR IV, 76reference, 76
Erglis, 262, 267reference, 270
FEMH-93005, 75FRE-RACE, 76FREEDOM, 113FUTURE I, 10, 30
reference, 51FUTURE II, 10, 30
reference, 50
GENESIS Trial CP-01, 75GISSOC II, 287
HAAMU-STENT, 118, 130reference, 139
Han, 12, 54reference, 64
In-stent restenosis, 213in-stent restenosis
available trials, 215excluded studies, 241main results, 219
ISAR-CABG, 257ISAR-DESIRE (PES vs PTCA), 216, 226
reference, 229ISAR-DESIRE (SES vs PES), 218, 237
reference, 240ISAR-DESIRE (SES vs PTCA), 216, 226
reference, 229ISAR-DIABETES, 81, 104
reference, 109ISAR-LEFT-MAIN, 271ISAR-SMART 3, 153, 167
reference, 172ISAR-test (diabetics), 82, 111
reference, 112ISAR-TEST-1, 12, 54
reference, 64
Kim, 81, 104reference, 109
Kochiadakis, 11, 33reference, 52
Korean Randomized Study, 75
LEADERS, 13, 67reference, 74
LEFT-MAIN-2, 271Leipzig, 271Lipsia-Yukon-DM, 113LONG DES II, 180, 203
reference, 208Long or complex lesion, 175long or complex lesion
available trials, 177excluded studies, 211main results, 181
MIDCAB Versus DES in Proximal LAD Le-sions, 75
MISSION, 118, 130reference, 139
Munich Study, 75
Nordic Bifurcation Stent Technique Study, 299Nordic Bifurcation Study, 299
Ortolani et al, 11, 32reference, 51
Pache et al, 11, 33reference, 52
Pan, 292, 296reference, 298
Pasceri, 118, 131reference, 139
PASSION, 118, 130reference, 139
PATENCY, 11, 32reference, 51
PEPCAD III, 75PEPCAD IV, 113PERSEUS WH, 75Petronio et al, 180, 203
reference, 208PRISON II, 276, 281
reference, 285PRISON III, 287
reference, 287PROSIT, 119, 141
reference, 146PROTECT, 75
RAVEL, 11, 34reference, 52
Ravel (diabetics), 80, 94reference, 102
REALITY, 12, 55reference, 64
REALITY (diabetics), 81, 104
INDEX 303
reference, 109RES-ELUTION, 75REVASCULARIZE, 75RRISC, 246, 252
reference, 256
SCANDSTENT, 178, 190reference, 196
SCORE, 10, 31reference, 51
SCORPIUS, 80, 93reference, 102
SES-SMART, 152, 161reference, 165
SES-SMARt (diabetics), 80, 94reference, 102
SESAMI, 118, 131reference, 139
SIRIUS, 11, 33reference, 52
SIRIUS (diabetics), 80, 94reference, 102
SIRTAX (small vessels subgroup), 153, 167reference, 172
SIRTAX (Windecker), 12, 55reference, 64
SIRTAX diabetics, 81, 104reference, 109
SISR, 217, 231reference, 235
Small vessels, 149small vessels
available trials, 151excluded studies, 173main results, 154
SORT OUT II, 12, 54reference, 64
SORT OUT IV, 75SPIRIT I, 10, 30
reference, 51SPIRIT II, 10, 31SPIRIT III, 10, 30
reference, 50SPIRIT IV, 76SYNTAX, 179, 198
TAXi, 12, 55reference, 65
TAxi (diabetics), 81, 104TAXUS I, 10, 31
reference, 51TAXUS II, 10, 31
reference, 51TAXUS II (diabetics), 80, 93
reference, 102TAXUS IV, 10, 31
reference, 51TAXUS IV (diabetics), 80, 93
reference, 102TAXUS V (all patients), 178, 190
reference, 196TAXUS V (diabetics), 80, 93
reference, 102TAXUS V ISR, 217, 231
reference, 235TAXUS VI, 178, 190
reference, 196TAXUS VI (diabetics), 80, 93
reference, 101Tomai, 81, 104
reference, 109Total occlusion, 273total occlusion
available trials, 275excluded studies, 287main results, 277
TRIAS-HR, 180, 203TRIAS-Low-Risk , 75TYPHOON, 118, 131
reference, 139
Unparticular patients, 7available trials, 9excluded studies, 75main results, 14
Unprotected left main coronary artery stenosis,259
unprotected left main coronary artery stenosisavailable trials, 261excluded studies, 271main results, 263
VELETI, 257
Wessely, 12, 54reference, 64
ZEST, 75ZEST AMI, 147Zhang (SES vs PES), 12, 54
reference, 64ZoMaxx phase 2, 75
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