isar-test-2 trial two-year clinical and angiographic outcomes from a randomized trial of...
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ISAR-TEST-2 Trial Two-year Clinical and Angiographic
Outcomes from a Randomized Trial of Polymer-Free Dual Drug-Eluting Stents
versus Polymer-Based Cypher and Endeavor Drug-Eluting Stents
Robert A. Byrne, MB MRCPIAdnan Kastrati, MD; Klaus Tiroch, MD; Stefanie Schulz, MD; Jürgen Pache, MD;
Susanne Pinieck; Steffen Massberg, MD; Melchior Seyfarth, MD; Karl-Ludwig Laugwitz, MD; Katrin A. Birkmeier, MD; Albert Schömig, MD; Julinda Mehilli, MD
ACC/i2 2010 – LBCT III
Deutsches Herzzentrum & 1. Med. Klinikum rechts der IsarTechnische Universität Munich Germany
Lecture fees from Medtronic
Presenter Disclosure Information
First generation DES systems deliver high antirestenotic efficacy in comparison with BMS but do so at the cost of a delay in structural and functional healing of stented segment
Background
*
Byrne, Joner, Kastrati Minerva Cardioangiol 2009
Incomplete Incomplete EndothelialisationEndothelialisation
Late Fibrin Late Fibrin DepositionDeposition
ChronicChronicInflammationInflammation
Platelet ActivationPlatelet Activation
Delayed Arterial Healing
*Incomplete Incomplete
EndothelialisationEndothelialisation
Late Fibrin Late Fibrin DepositionDeposition
ChronicChronicInflammationInflammation
Platelet ActivationPlatelet Activation
Delayed Arterial Healing
Inflammatory Response to Polymer
Residue May Play a Central Role
Byrne, Joner, Kastrati Minerva Cardioangiol 2009
Avoidance of polymer imposes efficacy limitations related to suboptimal drug release kinetics
The incorporation of a second active agent targeted at a different element of the restenotic response cascade is a potential option to enhance anti-restenotic performance
Probucol is a potent antioxidant which is also highly lipophilic and enhances the release kinetics of sirolimus
Background
to compare the anti-restenotic efficacy of:
polymer-free sirolimus+probucol-eluting stent (Dual-DES)
with
permanent polymer sirolimus-eluting stent (Cypher)
and
permanent polymer zotarolimus-eluting stent (Endeavor)
in patients with coronary artery disease
Aim of ISAR-TEST-2 Study
Inclusion Criteria “De novo” lesions in native coronary arteries Written informed consent
Exclusion Criteria Left main lesion Cardiogenic shock Comorbidities with a life expectancy < 12 months Contraindication to aspirin, limus agents, probucol,
stainless steel, thienopyridines
Patient Selection
Two-year Safety Endpoints:
Composite of death and myocardial infarction
Stent thrombosis according to ARC criteria
Two-year Efficacy Endpoints:
Target lesion revascularization (TLR) due to restenosis in the presence of symptoms or signs of ischemia
Composite binary restenosis at 2 years based on latest available angiogram (whether at 6-8 months or 2 years)
ISAR-TEST-2 Study Endpoints
1007 pts randomized
Dual-DES
333 pts
Endeavor
339 pts
Cypher
335 pts
942 pts (93.6%)with 2-year clinical FU*
828 pts (82.2%) with 6-8-mo. angiogram
*Among n=65 patients without 2-yr FU, median FU was 21 [20-22] months
493 pts (67.3% eligible)with 2-yr. angiogram
ISAR-TEST-2 Study Flow
Baseline Clinical Characteristics
Dual-DESn=333
Endeavorn=339
Data are percentage or mean ± standard deviation; Percentages may not total 100 due to rounding
Cyphern=335
Hypercholesterolemia 63 6669
Current smoker 20 1817
Diabetes 29 2627
Arterial hypertension 65 6864
Women 23 2523
67±11 67±11Age, years 67±11
History of MI 25 2630
LV ejection fraction (%)
Stable angina
Unstable angina
Acute MI
Dual-DESn=333
53±12
58
30
12
Endeavorn=339
55±10
56
30
15
Cyphern=335
52±12
61
25
13
Data are percentage or mean ± standard deviation; Percentages may not total 100 due to rounding
Baseline Clinical Characteristics
Target vesselLADLCxRCA
Complex lesions
Multivessel disease
Total occlusions
Data are percentage; percentages may not total 100 due to rounding
Dual-DESn=427
70
81
312544
12
Cyphern=419
73
86
2625
49
12
Endeavorn=420
75
83
2931
41
12
Angiographic Characteristics
QCA Measurements
Dual-DESn=427
Cyphern=419
Endeavorn=420
Vessel size, mm 2.75±.46 2.71±.492.69±.52
Lesion length, mm 14.8±8.3 14.7±8.014.0±8.2
MLD after PCI, mm 2.55±.43 2.51±.472.49±.48
DS after PCI, % 10.8±5.7 10.7±7.011.6±5.0
Data are mean ± standard deviation
ISAR-TEST-2
Primary Results
ISAR-TEST-2 Eur Heart J 2009
ISAR-TEST-2
12.011.0
19.3
0
5
10
15
20
EndeavorCypher Dual-DES
p=0.003
6-8 months
%
Binary Angiographic Restenosis
12.011.0
19.3
0
5
10
15
20
EndeavorCypher Dual-DES
%
p=0.68 p=0.002
Binary Angiographic Restenosis6-8 months
ISAR-TEST-2
Two-year Results
0
10
20
30
40
50
0 2 4 6 8 10 12 14 16 18 20 22 24
%
mos
p=0.61
Death or myocardial infarction
Dual-DES 7.8%Endeavor ZES 9.2%
Cypher SES 10.2%
0.3
1.2 1.2
0.6 0.6 0.60.9
0.0
0.9
0
2
4
6
Incidence
Definite Probable Possible
p=0.67p=0.37p=0.87
EndeavorCypher Dual-DES
%
Stent Thrombosis at 2 years
13.6
6.87.2
14.3
7.7
10.7
0
5
10
15
20
25
1 yr 2 yrs
EndeavorCypher Dual-DES
p=0.009
1 yr 2 yrs 1 yr 2 yrs
%
Target Lesion Revascularization
13.6
6.87.2
14.3
7.7
10.7
0
5
10
15
20
25
1 yr 2 yrs
Δ = 3.5% Δ = 0.7%Δ = 0.9%
EndeavorCypher Dual-DES
p=0.009 p=0.72
1 yr 2 yrs 1 yr 2 yrs
%
Target Lesion Revascularization
19.3
11.012.0
20.9
13.9
18.8
0
5
10
15
20
25
30
6-8 m 2 yrs*
%
6-8 m 2 yrs* 6-8 m 2 yrs*
Binary restenosis
EndeavorCypher Dual-DES
p=0.045
19.3
11.012.0
20.9
13.9
18.8
0
5
10
15
20
25
30
6-8 m 2 yrs*
%Δ = 6.8% Δ = 1.6%Δ = 2.9%
p=0.016 p=0.28
6-8 m 2 yrs* 6-8 m 2 yrs*
Binary restenosis
EndeavorCypher Dual-DES
The occurrence of safety events beyond 1 year was rare; there was no signal of a differential safety profile between the Dual-DES, Cypher and Endeavor out to 2 years
The antirestenotic efficacy of both Dual-DES and Endeavor remained durable between 1 and 2 years with Dual-DES maintaining an edge
There was evidence of a slight decrement in efficacy with Cypher from 1 to 2 years
Conclusions
ISAR-TEST-2 TrialDeutsches Herzzentrum, Munich. Germany
Thank You
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