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
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Lecture fees from Medtronic
Presenter Disclosure Information
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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
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*
Byrne, Joner, Kastrati Minerva Cardioangiol 2009
Incomplete Incomplete EndothelialisationEndothelialisation
Late Fibrin Late Fibrin DepositionDeposition
ChronicChronicInflammationInflammation
Platelet ActivationPlatelet Activation
Delayed Arterial Healing
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*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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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ISAR-TEST-2
Primary Results
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ISAR-TEST-2 Eur Heart J 2009
ISAR-TEST-2
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12.011.0
19.3
0
5
10
15
20
EndeavorCypher Dual-DES
p=0.003
6-8 months
%
Binary Angiographic Restenosis
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12.011.0
19.3
0
5
10
15
20
EndeavorCypher Dual-DES
%
p=0.68 p=0.002
Binary Angiographic Restenosis6-8 months
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ISAR-TEST-2
Two-year Results
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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%
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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
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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
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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
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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
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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
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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
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ISAR-TEST-2 TrialDeutsches Herzzentrum, Munich. Germany
Thank You