syntax - top 30 enrolling centers: i - bcis.org.uk · andrejs bochenek janus drzewiecki elisabeth...

SYNTAX - Top 30 Enrolling Centers: I

CABG Investigator PCI Investigator

Paul Simon Dietmar Glogar

Jan Tosovsky Michael Aschermann

Per Nielsen Hostrup Leif Thuesen

Gerard Fournial Didier Carrie

Arnaud Farge Marie-Claude Morice

Jean-Paul Bessou Jacques Berland

Patrick Soula Jean Marco

Friedrich Mohr Gerhard Schuler

Bruno Reichart Peter Boekstegers

Hermann Reichenspurner Thomas Meinertz

Lajos Papp Ivan G. Horvath

Ferenc Tarr Istvan Preda

Paolo Ferrazzi Giulio Guagliumi

Andrea d’Armini Ezio Bramucci

Lucia Torracca Antonio Colombo

Austria

Czech Rep

Norway

France

Germany

Hungary

Italy

CABG Investigator PCI Investigator

Mattia Glauber Sergio Berti

Romans Lacis Andrejs Erglis

Pieter Kappetein Patrick Serruys

Jacques Schonberger Jacques Koolen

Andrejs Bochenek Janus Drzewiecki

Elisabeth Stahle Stefan James

Stephen Westaby Adrian Banning

Geoff Berg Keith G. Oldroyd

Steven Livesey Keith D. Dawkins

Jatin Desai Martyn Thomas

Tomasz Spyt Anthony H. Gershlick

Andrew Forsyth Adam De Belder

Graham Venn Simon Redwood

William Killinger Tift Mann

Michael Mack David L. Brown

SYNTAX - Top 30 Enrolling Centers: II

Italy

Latvia

Netherlands

Poland

Sweden

UK

US

SYNTAX

Heart team meeting - surgeon(s) and interventional cardiologist(s) assess each patient

Operative risk (EuroSCORE & Parsonnet score)

Coronary lesion complexity (SYNTAX score)

Sianos et al, EuroIntervention 2005;1:219-227 Valgimigli et al, Am J Cardiol 2007;99:1072-1081 Serruys et al, EuroIntervention 2007;3:450-459

BARI classification of coronary segments Leaman score, Circ 1981;63:285-299 Lesions classification ACC/AHA , Circ 2001;103:3019-3041 Bifurcation classification, CCI 2000;49:274-283 CTO classification, J Am Coll Cardiol 1997;30:649-656

No. &

Location

of lesion Left

Main

Tortuosity

3 Vessel Thrombus

Bifurcation CTO

Calcification

SYNTAX

SCORE

Dominance

Isolated left main

Limited Exclusion Criteria Previous interventions (PCI or CABG) Acute MI with CPK>2x Concomitant cardiac surgery

SYNTAX Trial- Eligible Patients

De novo disease

Revascularisation in all 3 vascular territories

3-vessel disease

left main + 1-vessel disease



71% enrolled (N=3,075)

All Pts with de novo 3VD and/or LM disease (N=4,337)

Treatment preference (9.4%)

Referring doctor or patient refused informed consent (7.0%)

Inclusion/exclusion (4.7%)

Withdrew before consent (4.3%)

Other (1.8%)

Medical treatment (1.2%)

23 US Sites 62 EU Sites +

SYNTAX Trial Design

TAXUS n=903

PCI n=198

CABG n=1077

CABG n=897

no f/u n=428

5yr f/u n=649

PCI all captured w/

follow up

CABG 2500

750 w/ f/u vs

Total enrollment N=3075

Stratification: LM and Diabetes

Two Registry Arms

Randomized Arms n=1800

Two Registry Arms

Randomised Arms n=1800

Heart Team (surgeon & interventionalist)

PCI N=198

CABG N=1077

Amenable for only one treatment approach

TAXUS*

N=903 CABG

N=897 vs

Amenable for both treatment options


LM 33.7%

3VD 66.3%

LM 34.6%

3VD 65.4%


SYNTAX Trial Design

71% enrolled (N=3,075)

All Pts with de novo 3VD and/or LM disease (n=4,337)

Treatment preference (9.4%)

Referring MD or pts. refused informed consent (7.0%)

Inclusion/exclusion (4.7%)

Withdrew before consent (4.3%)

Other (1.8%)

Medical treatment (1.2%) TAXUS n=903

PCI n=198

CABG n=1077

CABG n=897

no f/u n=428

5yr f/u n=649

PCI all captured w/

follow up

CABG 2500

750 w/ f/u vs

Total enrollment N=3075


Two Registry Arms

Randomized Arms n=1800

Two Registry Arms

Randomised Arms n=1800

Heart Team (surgeon & interventionalist)

PCI N=198

CABG N=1077

Amenable for only one treatment approach

TAXUS*

N=903 CABG

N=897 vs

Amenable for both treatment options


LM 33.7%

3VD 66.3%

LM 34.6%

3VD 65.4%

DM 28.5%

Non DM 71.5%

NonDM 71.8%

DM 28.2%


SYNTAX Trial Design

Withdrawn 47 Lost to FU 13

12 mo Follow up N=1740 (96.7%)

Total randomized N=1800

TAXUS*

891 (98.7%)

7 5

TAXUS*

903 (50.2%)

CABG 897 (49.8%)

CABG 849 (94.6%)

40 8

Randomised Patient Flow (ITT)

Patient Characteristics (l) Randomised Cohort

CABG N=897

TAXUS* N=903

P value

Age, mean ± SD (y) 65.0 ± 9.8 65.2 ± 9.7 0.55

Male, % 78.9 76.4 0.20

BMI, mean ± SD 27.9 ± 4.5 28.1 ± 4.8 0.37

Diabetes, % 28.5 28.2 0.89

Hypertension, % 77.0 74.0 0.14

Hyperlipidemia, % 77.2 78.7 0.44

Current smoker, % 22.0 18.5 0.06

Prior MI, % 33.8 31.9 0.39

Unstable angina, % 28.0 28.9 0.67

Additive EuroSCORE, mean ± SD 3.8 ± 2.7 3.8 ± 2.6 0.78

Total Parsonnet score , mean ± SD 8.4 ± 6.8 8.5 ± 7.0 0.76

Patient Characteristics (lI) Randomised Cohort

Patient-based

CABG N=897

TAXUS* N=903

P value

Total SYNTAX Score 29.1 ±11.4 28.4 ±11.5 0.19

Diffuse disease or small vessels, % 10.7 11.3 0.69

No. lesions, mean ± SD 4.4 ±1.8 4.3 ±1.8 0.44

3VD only, % 66.3 65.4 0.70

Left main, any, % 33.7 34.6 0.70

Left Main only 3.1 3.8 0.46

Left Main + 1 vessel 5.1 5.4 0.78



Total occlusion, % 22.2 24.2 0.33

Bifurcation, % 73.3 72.4 0.67

Trifurcation, % 10.6 10.7 0.92

Baseline Characteristics in DES Patients SYNTAX Trial Versus 2 Large, Multicenter MVD Registries

ARTS II

N=607

NY State

N=9963

SYNTAX

N=903

Age, mean±SD (y) 63 ± 10 65.4 ± 11.9 65.2 ± 9.7

Male, % 77 67.2 76.4

BMI, mean±SD 27.5 ± 4.1 - 28.1 ± 4.8

Diabetes, % 26 32.7 28.2

Hypertension, % 67 - 74.0

Hyperlipidemia, % 74 - 78.7

Current smoker, % 19 - 18.5

Prior MI, % 34 33.7 31.9

History of CHF, % - 10.1 4.0

Renal Failure* - 1.4 1.1

Left Main, % excluded excluded 35%

3 Vessel Disease, % 54% 25% 91%

*Creatinine >220µmol/liter for NY State, >200µmol/liter for the SYNTAX trial

Patient-based

TAXUS* N=903

Staged Procedure, % 14.1

Vessels treated, %

LAD 36.3

Circumflex 32.5

RCA 29.2

LM 11.2

Bi/trifurcation, % 64.4

Lesions treated/pt, mean ± SD 3.6 ± 1.6

No. stents implanted, mean ± SD 4.6 2.3

Total length implanted, mm ± SD 86.1 47.9

Range, mm 8 – 324

Long stenting (>100 mm), % 33.2

Procedural Characteristics PCI Randomised Cohort

Procedure-related CABG

N=897

Off-pump surgery, % 15.0

Graft revascularization, %

Complete arterial revascularisation 18.9

At least one arterial graft 97.3

Double LIMA/RIMA 27.6

LIMA+venous 78.1

Arterial graft to LAD 95.6

Radial Artery 14.1

Venous graft only 2.6

Grafts per patient, mean ± SD 2.8 0.7

Distal anastomosis/pt, mean ± SD 3.2 0.9

Procedural Characteristics CABG Randomised Cohort

Procedural Characteristics Randomised Cohort

CABG N=897

TAXUS* N=903

P value

Time to procedure*, d, mean ± SD 17.4 ± 28.0 6.9 ± 13.0 <0.001

Procedure duration†, hr, mean ± SD 3.4 ± 1.1 1.7 ± 0.9 <0.001

Post-procedure IP stay†, d, mean ± SD

14.0 ± 10.6 6.8 ± 7.7 <0.001

Revascularisation, %

Complete‡ 63.2 56.7 0.005

Incomplete 36.8 43.3 0.005

*Allocation to procedure †For PCI patients, includes time for staged procedure

Per protocol: ‘Complete revascularisation is defined as the treatment of any

lesion with more than 50% diameter stenosis in vessels 1.5 mm diameter as estimated on the diagnostic angiogram during the local Heart Team conference’. Completeness of revascularization was assessed post procedure by the operator (Surgeon or Interventional Cardiologist)

‡

ITT; ¥Fisher Exact Test

P=0.37¥

SYNTAX - All-cause mortality to 12 Months

4.3%

3.5%

0 6 12

10

20

0

Months Since Allocation

Cum

ula

tive E

vent

Rate

(%

)

TAXUS* (N=903) CABG (N=897)

SYNTAX - Cerebrovascular Events to 12 Months

0.6%

2.2%

0 6 12

10

20

0


Cum

ula

tive E

vent

Rate

(%

)


P=0.003¥


SYNTAX - Myocardial Infarction to 12 Months

3.2% 4.8%

0 6 12

10

20

0


Cum

ula

tive E

vent

Rate

(%

)


P=0.11¥


SYNTAX - Death/CVA/MI to 12 Months

P=0.98¥

0 6 12

10

20

0


Cum

ula

tive E

vent

Rate

(%

)

7.7% 7.6%



SYNTAX - Symptomatic Graft Occlusion & Stent Thrombosis at 12 Months

3.3 3.4

P=0.89

CABG TAXUS

Pati

ents

(%

)

n=27 n=28


ITT population

SYNTAX - Repeat Revascularisation to 12 Months

5.9%

13.7%

0 6 12

10

20

0


Cum

ula

tive E

vent

Rate

(%

)


P<0.0001¥


Repeat Revasc

CABG Group

PCI Group

PCI 4.7% 11.4%

CABG 1.3% 2.8%

SYNTAX - MACCE to 12 Months

P=0.0015¥

0 6 12

10

20

0


Cum

ula

tive E

vent

Rate

(%

)

12.1%

17.8%



SYNTAX - 12 Month Clinical Event Rates

Patients (%)

CABG (N=897) TAXUS* (N=903)

ITT, Kaplan-Meier Rates; Fisher Exact Test

All Death

CVA

MI

Death/MI/CVA

Revascularisation

P=0.37

P=0.003

P=0.11

P=0.98

P<0.0001

3.5

2.2

3.2

7.7

5.9

4.3

0.6

4.8

7.6

13.7

Primary Endpoint: 12 Month MACCE Non-inferiority analysis

Non-inferiority comparison was not met for the primary endpoint, further comparisons for the LM and 3VD subgroups are observational only and hypothesis generating

0 5% 10% 15%

Pre-specified Margin = 6.6%

Difference in MACCE

20%

+95% CI = 8.3% 5.5%

48% of patients received ≥5 stents

Max #

14 stents!

Stent Number and Length Higher in the SYNTAX Trial

0

5

10

15

20

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pa

tie

nts

(%

)

Total Number of Stents Implanted per Patient

Multivessel disease: 96.2%*

3-vessel disease: 90.8%

Avg. stents per patient: 4.6 ± 2.3

Avg. stented length: 86.1 mm

*3VD+LM/3VD+LM/2VD+LM/1VD

Average Number of Stents Implanted per Patient

0

1

2

3

4

5

MA

IN-C

OM

PA

RE

Ho

ng 2

005

ER

AC

I II

Ben-G

al 2006

LE

MA

NS

So

SN

aple

s R

egis

try

Cedars

-Sin

ai

Cle

vela

nd C

linic

AR

TS

IS

eo

ul R

egis

try

Yan

g, 2007

AR

TS

II

SY

NTA

X

Avg. # s

tents

or

lesio

ns tre

ate

d

4.6±2.3

SYNTAX

Trial Average number of stents implanted

in SYNTAX is higher than any other

contemporary DES versus CABG study

Average Total Stented Length

0

20

40

60

80

100

MA

IN-C

OM

PA

RE

Hong 2

005

Naple

s R

egis

try

Cedars

-Sin

ai

AR

TS

I

Seoul R

egis

try

AR

TS

II

SY

NTA

X

86.1±47.9

SYNTAX

Trial

Avera

ge tota

l ste

nt

length

(m

m)

Linear Increase in MACCE by Number of Stents in the SYNTAX Trial

0.00

0.05

0.10

0.15

0.20

0.25

0.30

12

m M

AC

CE

in

TA

XU

S A

rm

1 2 3 4 5 6 7 8+

Number of Stents Implanted

12m MACCE Probability

12m MACCE Rate

4.6 Stents

SYNTAX Average

17.8%

1.5 Stents

“Typical” Real

World Average

1 stent

5.6%

Avg. in pts with

5-8+ stents

in SYNTAX

19.6%

SYNTAX - Outcome according to Diabetic Status

Diabetes (Medical Treatment)

N=452

Non-Diabetic

N=1348

TAXUS CABG

Death/CVA/MI MACCE Death/CVA/MI MACCE

P=0.96 P=0.0025 P=0.08 P=0.97

SYNTAX - Left Main Subgroup MACCE Rates at 12 Months

Left Main Isolated

Left Main + 3VD

Left Main + 2VD

Left Main + 1VD

N=258

(37%)

N=218

(31%)

N=138

(20%)

N=91

(13%)

CABG TAXUS*

Pati

ents

(%

)

All LM N=705

SYNTAX - Left Main and Three Vessel Disease Subgroup MACCE Rates at 12 Months

CABG TAXUS*

Pati

ents

(%

)

All LM N=705

LM+1VD N=138

LM Isolated N=91

LM+2VD N=218

LM+3VD N=258

3VD ( w/o LM) N=1095

Contemporary studies of DES versus CABG 1-Year Mortality in CABG Arm

3.2 2.7

8.0

3.1 3.5

8.4

12.3

15.2

6.4

0

5

10

15

20Multivessel Left Main

Yang

2008

(n=390)

ARTS I

(n=602)

Lee, 2007

(n=103)

Javaid

2008

(n=505)

SYNTAX

Trial

(n=897)

Sanmartin

2007

(n=245)

Palmerini

2006

(n=154)

Lee

2006

(n=123)

Chieffo

2006

(n=142)

Patients

(%

)

Multivessel

and/or

Left Main

Contemporary studies of DES versus CABG 1-Year TVR (PCI or CABG) in CABG Arm

0.8

3.73.0

5.9

0.8

2.6

5.5

3.6

0

2

4

6

8

10

Multivessel Left Main

Lee

2007

(n=103)

Sanmartin

2007

(n=245)

Palmerini

2006

(n=154)

Lee

2006

(n=123)

Chieffo

2006

(n=142)

Patients

(%

)

ARTS I

(n=602)

Yang

2008

(n=390)

SYNTAX

Trial

(n=897)

Multivessel

and/or

Left Main

Contemporary studies of DES versus CABG 1-Year Stroke Rates in CABG Arm

0.8

1.8

4.0

1.0

2.2

0.8 0.7

0

1

2

3

4

5 Multivessel Left Main

Lee

2007

(n=103)

Javaid

2008

(n=505)

Sanmartin

2007

(n=245)

Chieffo

2006

(n=142)

Patients

(%

)

ARTS I

(n=602)

Yang

2008

(n=390)

SYNTAX

Trial

(n=897)

Multivessel

and/or

Left Main

Contemporary studies of DES versus CABG 1-Year MAC(C)E* Rates in CABG Arm

4.2

11.6 12.010.8

12.411.4

24.8

0

5

10

15

20

25

30


Lee

2007

(n=103)

Javaid

2008

(n=505)

*definitions vary

across studies

Sanmartin

2007

(n=245)

Lee

2006

(n=123)

Patients

(%

)

ARTS I

(n=602)

Yang

2008

(n=390)

SYNTAX

Trial

(n=897)

Multivessel

and/or

Left Main

Average Stent Number and Length in ARRIVE Registry (N=7,492 patients)

0

20

40

60

80

0 1 2 3 4 5 ≥6 7 8 9 10 11 12 13 14

Pa

tie

nts

(%

)


Multivessel disease: 36.9%

3-vessel stenting: 1.2%



Average Stent Number and Length in OLYMPIA Registry (N=22,345 patients)

0

20

40

60

80

0 1 2 3 4 5 ≥6 7 8 9 10 11 12 13 14

Pa

tie

nts

(%

)


Multivessel disease: 56.5%

3-vessel stenting: 1.3%



48% of patients received ≥5 stents

Max #

14 stents!

Stent Number and Length Higher in the SYNTAX Trial

0

5

10

15

20

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Pa

tie

nts

(%

)


Multivessel disease: 96.2%*

3-vessel disease: 90.8%



*3VD+LM/3VD+LM/2VD+LM/1VD

Average Number of Stents Implanted per Patient

0

1

2

3

4

5

MA

IN-C

OM

PA

RE

Ho

ng 2

005

ER

AC

I II

Ben-G

al 2006

LE

MA

NS

So

SN

aple

s R

egis

try

Cedars

-Sin

ai

Cle

vela

nd C

linic

AR

TS

IS

eo

ul R

egis

try

Yan

g, 2007

AR

TS

II

SY

NTA

X

Avg. # s

tents

or

lesio

ns tre

ate

d

4.6±2.3

SYNTAX

Trial Average number of stents implanted

in SYNTAX is higher than any other

contemporary DES versus CABG study

Average Total Stented Length

0

20

40

60

80

100

MA

IN-C

OM

PA

RE

Hong 2

005

Naple

s R

egis

try

Cedars

-Sin

ai

AR

TS

I

Seoul R

egis

try

AR

TS

II

SY

NTA

X

86.1±47.9

SYNTAX

Trial

Avera

ge tota

l ste

nt

length

(m

m)

Linear Increase in MACCE by Number of Stents in the SYNTAX Trial

0.00

0.05

0.10

0.15

0.20

0.25

0.30

12

m M

AC

CE

in

TA

XU

S A

rm

1 2 3 4 5 6 7 8+

Number of Stents Implanted

12m MACCE Probability

12m MACCE Rate

4.6 Stents

SYNTAX Average

17.8%

1.5 Stents

“Typical” Real

World Average

1 stent

5.6%

Avg. in pts with

5-8+ stents

in SYNTAX

19.6%

2.0

7.2

2.3

4.94.2

9.8

4.4

13.5

0

2

4

6

8

10

12

14

16

1-Year Mortality and Revascularisation Rates in TAXUS Stent Studies

Pa

tie

nts

(%

)

Mortality Revascularisation

TAXUS

SR

Meta

ARRIVE

Simple

Use

ARRIVE

MV

Stenting

SYNTAX

Trial

TAXUS

SR

Meta

ARRIVE

Simple

Use

ARRIVE

MV

Stenting

SYNTAX

Trial

Target vessel only

Any R

epeat R

evascula

rization

Contemporary studies of DES versus CABG 1-Year Revascularisation in DES Arm

10.28.5

26.0

13.5

10.0

5.2

25.5

13.3

19.6

0

10

20

30


Yang

2008

(n=441)

ARTS II

(n=607)

Hannan

2008

(n=9963)

DELFT

2008

(n=358)

Sanmartin

2007

(n=96)

Palmerini

2006

(n=157)

Lee

2006

(n=50)

Chieffo

2006

(n=107)

Patients

(%

)

42%

3VD

91%

3VD

54%

3VD

35%

LM

25%

3VD (TVR) (TVR) (TLR) (TVR)

All Revasc.

All Revascularization

SYNTAX

Trial

(n=903)

Multivessel

and/or

Left Main

(All)

Contemporary studies of DES versus CABG 1-Year Mortality in DES Arm

2.11.0

10.0

4.9

10.9

4.4

6.75.2

13.4

4.4

2.8

0

5

10

15


Yang

2008

(n=441)

ARTS II

(n=607)

Lee, 2007

(n=102)

Hannan

2008

(n=9963)

Javaid

2008

(n=95)

(cardiac)

DELFT

2008

(n=358)

Sanmartin

2007

(n=96)

Palmerini

2006

(n=157)

Lee

2006

(n=50)

Chieffo

2006

(n=107)

Patients

(%

)

SYNTAX

Trial

(n=903)

Multivessel

and/or

Left Main

Contemporary studies of DES versus CABG 1-Year Stroke Rates in DES Arm

0.7

1.0

0.0

1.1

0.6

0.0

0.9

0

1

2


Yang

2008

(n=441)

ARTS II

(n=607)

Lee

2007

(n=102)

Javaid

2008

(n=95)

Sanmartin

2007

(n=96)

Chieffo

2006

(n=107)

Patients

(%

)

SYNTAX

Trial

(n=903)

Multivessel

and/or

Left Main

Contemporary studies of DES versus CABG 1-Year MAC(C)E* Rates in DES Arm

13.0

10.4

27.028.2

19.2

15.8

24.3

10.4

17.1

0

5

10

15

20

25

30

35


Yang

2008

(n=441)

ARTS II

(n=607)

Lee

2007

(n=102)

Javaid

2008

(n=95)

DELFT

2008

(n=358)

*definitions vary

across studies

Sanmartin

2007

(n=96)

Lee

2006

(n=50) SYNTAX Trial

Patients

(%

)

3VD LM

Atherosclerosis: A progressive process

Disease progression

PHASE I: Initiation PHASE II: Progression PHASE III: Complication

Atherosclerotic progression: Glagov’s remodeling hypothesis

Normal

vessel

Progression

Glagov S, et al. N Engl J Med. 1987;316:1371-1375.

Moderate

CAD

Compensatory expansion

maintains constant lumen

Minimal

CAD

Expansion

overcome:

lumen narrows

Advanced

CAD

What types of lesions cause MI?

Falk E, et al. Circulation. 1995;92:657-671.

100

80

60

40

20

0

14%

18%

68%

All 4

studies

50%-70% <50% >70%

100

60

40

20

0

Ambrose

1988

Little

1988

Nobuyoshi

1991

Giroud

1992

Coro

nary

ste

nosis

(%

)

Coronary stenosis severity prior to MI

80

Atherosclerosis: The first sign of CHD is often sudden death or MI

0

62% (552/895 men) Men

45% (305/674 women) Women

Patients who experienced an MI (%)

Murabito JM, et al. Circulation. 1993;88:2548-2555.

20 30 40 50 60 70 10

Breakdown of Current CAD Treatment

CDC MMWR 2007;56:113-118

Eur Heart J 2005;26:1011-1022

J Am Coll Cardiol 2002;39:1096-1103

US Europe

91%

7%

2%

Medical Rx

PCI

CABG

85%

8%6%

1%Medical Rx

PCI

CABG

PCI + CABG

CABG is the current gold-standard of care in patients with left main & multivessel disease

Isolated LM includes portion of ostial LAD and CX. A lesion

would have to be 3x RVD away from another lesion to count as

a separate lesion. So if lesion originates in LM and extends to

both LAD and CX that would be a LM isolated. Only when the

RVD criteria is met further down vessel, or obviously RCA, does

it count as +1/2/3.

syntax - top 30 enrolling centers: i - bcis.org.uk · andrejs bochenek janus drzewiecki elisabeth...

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