Post on 18-Jan-2016
description
Two-Year Outcomes After Two-Year Outcomes After Everolimus- or Sirolimus-Everolimus- or Sirolimus-
Eluting Stents in Patients With Eluting Stents in Patients With Coronary Artery DiseaseCoronary Artery Diseasein the ISAR-TEST 4 Trialin the ISAR-TEST 4 Trial
Robert A. ByrneRobert A. Byrne, Adnan Kastrati, Klaus Tiroch, Steffen , Adnan Kastrati, Klaus Tiroch, Steffen Massberg, AnnaMassberg, Anna Wieczorek Wieczorek, Karl-Ludwig Laugwitz, , Karl-Ludwig Laugwitz,
Stefanie Schulz, Jürgen Pache, Massimiliano Fusaro, Stefanie Schulz, Jürgen Pache, Massimiliano Fusaro, Melchior Seyfarth, Albert Schömig, Julinda MehilliMelchior Seyfarth, Albert Schömig, Julinda Mehilli
Deutsches Herzzentrum & 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität, Munich. Germany
Nothing to discloseNothing to disclose
Presenter Disclosure Information:Presenter Disclosure Information:
• In head-to-head randomized trials, In head-to-head randomized trials, everolimus-everolimus-eluting stent (EES; Xience)eluting stent (EES; Xience) has proven superior has proven superior to the pacliaxel-eluting stent (PES; Taxus)to the pacliaxel-eluting stent (PES; Taxus)
BackgroundBackground
4.2
6.8
0
5
10
Xience EES
Taxus PES
Cardiac death, TV MI, TLR, %
SPIRIT IV
Stone et al. NEJM 2010
6.2
9.1
0
4
8
12
COMPARE
Kedhi et al. Lancet 2010
Xience EES
Taxus PES
Death, MI, TVR (%)
RR 0.62 [95% CI 0.46-0.82];
P= 0.001
RR 0.69 [95% CI 0.50-0.95];
P= 0.02
BackgroundBackground
• Significant differences exist between Significant differences exist between first-generation DESfirst-generation DES
• A more appropriate comparator device A more appropriate comparator device is is sirolimus-eluting stent (SES; Cypher)sirolimus-eluting stent (SES; Cypher) due to its high antirestenotic efficacy due to its high antirestenotic efficacy and its similar limus-based drug-elution and its similar limus-based drug-elution strategystrategy
Schömig JACC 2007; Stettler Lancet 2007; Gurm AHJ 2008Schömig JACC 2007; Stettler Lancet 2007; Gurm AHJ 2008
Biodegradable polymer DES(BP-DES)n=1299
Permanent polymer DES(PP-DES: Xience & Cypher)
n=1304
2603 patients with de novo lesions
Intracoronary Stenting and Angiographic Results:Test Efficacy of 3 Limus-Eluting Stents - 4
6-8 month & 2 year FU angiography
24-month clinical follow-up
ISAR-TEST 4 Study AlgorithmISAR-TEST 4 Study Algorithm
Byrne et al. Eur Heart J 2009
Primary: To compare the efficacy of biodegradable polymer DES against permanent polymer DES
Secondary: To compare the efficacy of – everolimus-eluting stent (Xience) and – sirolimus-eluting stent (Cypher)
Objectives of ISAR-TEST 4Objectives of ISAR-TEST 4
Byrne et al. Eur Heart J 2009
ISAR-TEST 4 EES vs. SESISAR-TEST 4 EES vs. SES
Design
• DESIGN: Investigator-initiated, industry-independent, randomized, two-center clinical trial
• INCLUSION: Patients with de novo coronary artery stenosis ≥ 50% AND symptoms or objective evidence of ischaemia
• EXCLUSION CRITERIA: Left main stem disease
Cardiogenic shock
1304 patients enrolled at 2 centres in Munich, Germany
Angio follow-up at 6-8 months in 77%†
Angio follow-up at 2 years in 70%†
Angio follow-up at 6 months in 79%†
Angio follow-up at 2 years in 68%†
Clinical follow-up at 2 years in 94%*
Clinical follow-up at 2 years in 95%*
† of eligible* of incomplete, median FU = 12 [3-16] mos
652 treated with EES (Xience)
652 treated with SES (Cypher)
Primary: Composite of cardiac death, target vessel MI or TLR at 2 years
Secondary: All cause mortality Stent thrombosis (ARC definite/probable)Binary restenosis (in-segment)Late luminal loss (in-stent)
ISAR-TEST 4 EndpointsISAR-TEST 4 Endpoints
Xience-VXience-V
n=652n=652
CypherCypher
n=652n=652
Age, yearsAge, years 66.766.7±±11.111.1 66.866.8±±10.310.3
Male, %Male, % 7878 7676
Art. hypertension, %Art. hypertension, % 6868 6767
Diabetes, %Diabetes, % 2828 3030
Current smoker, %Current smoker, % 1616 1818
Prior bypass surgery, %Prior bypass surgery, % 1111 99
Prior MI, %Prior MI, % 2929 2828
Hyperlipidemia, %Hyperlipidemia, % 6565 6565
Baseline clinical characteristics, IBaseline clinical characteristics, I
Xience-VXience-V
n=652n=652
CypherCypher
n=652n=652
Clinical presentation, %*Clinical presentation, %*
acute MIacute MI 1111 1111
unstable anginaunstable angina 3131 2828
stable anginastable angina 5959 6262
Multivessel disease, %Multivessel disease, % 8585 8787
Multilesion PCI, %Multilesion PCI, % 2727 2525
LV ejection fraction, %LV ejection fraction, % 53.453.4±±12.112.1 53.853.8±±11.711.7
* Due to rounding totals do not equal 100* Due to rounding totals do not equal 100
Baseline clinical characteristics, IIBaseline clinical characteristics, II
Xience-VXience-V
n=850n=850
CypherCypher
n=839n=839
Target vessel, %Target vessel, %
left anterior descendingleft anterior descending 4444 4545
left circumflexleft circumflex 2626 2727
right coronary arteryright coronary artery 3030 2828
Bifurcation, %Bifurcation, % 2222 2424
Complex morphology, %Complex morphology, % 7171 7373
Lesion length, mmLesion length, mm 15.215.2±±8.28.2 14.814.8±±8.98.9
Vessel size, mmVessel size, mm 2.802.80±±0.480.48 2.802.80±±0.450.45
Angiographic characteristicsAngiographic characteristics
Xience-VXience-V
n=850n=850
CypherCypher
n=839n=839
Stenosis pre-procedure, %Stenosis pre-procedure, % 64.964.9±16.0±16.0 65.465.4±16.1±16.1
Max ballon pressure, atmMax ballon pressure, atm 15.715.7±3.1±3.1 15.215.2±3.2±3.2
Balloon vessel ratioBalloon vessel ratio 1.11.1±.1±.1 1.11.1±.1±.1
Stenosis post-procedure, in-stent, %Stenosis post-procedure, in-stent, % 11.811.8±6.3±6.3 10.810.8±±6.26.2
Stenosis post-procedure, in-seg, %Stenosis post-procedure, in-seg, % 23.623.6±11.4±11.4 23.323.3±11.4±11.4
Procedural characteristicsProcedural characteristics
Everolimus-eluting stent, 16.0%
Sirolimus-eluting stent, 18.8%
0 2 4 6 8 10 12 14 16 18 20 22 24Months after randomization
0
20
40
60
80
100
Cardiac Death, Target Vessel MI, TLRCardiac Death, Target Vessel MI, TLR
RR 0.85 [95% CI, 0.65-1.11], P=0.23%
Everolimus-eluting stent, 6.4%
Sirolimus-eluting stent, 6.7%
0
2
4
6
8
10
All Cause DeathAll Cause Death
0 2 4 6 8 10 12 14 16 18 20 22 24
RR 0.93 [95% CI, 0.61-1.43]; P=0.75%
Months after randomization
0
1
2
3
4
5
Everolimus-eluting stent, 1.4%
Sirolimus-eluting stent, 1.9%
0 2 4 6 8 10 12 14 16 18 20 22 24Months after randomization
Definite or Probable Stent ThrombosisDefinite or Probable Stent Thrombosis
RR 0.75 [95% CI, 0.32-1.78], P=0.52%
Definite Stent ThrombosisDefinite Stent Thrombosis
3
2
5
2
1
0 2 4 6 8 10
Early (<30d)
Late (30d-1y)
V. late (>1y)EES
(0.6%)
SES(1.4%)
P=0.17
0 2 4 6 8 10 12 14 16 18 20 22 24Months after randomization
0
20
40
60
80
100
Everolimus-eluting stent, 9.9%
Sirolimus-eluting stent, 13.5%
%
Target Lesion RevascularizationTarget Lesion Revascularization
RR 0.73 [95% CI, 0.52-1.01], P=0.06
8.1
10.79.9
13.5
0
5
10
15
20
25
Δ = 1.8% Δ = 2.8%
EES SES
P=0.25
Target Lesion RevascularizationTarget Lesion Revascularization
%
1 yr 2 yrs 1 yr 2 yrs
10.1
13.412.7
16.9
0
5
10
15
20
25
6-8 m 2 yrs*
P=0.03
6-8 m 2 yrs*
Binary Angiographic RestenosisBinary Angiographic Restenosis
EES SES* = composite
%
10.1
13.412.7
16.9
0
5
10
15
20
25
6-8 m 2 yrs*
Δ = 2.6% Δ = 3.5%
P=0.37
6-8 m 2 yrs*
Binary Angiographic RestenosisBinary Angiographic Restenosis
EES SES* = composite
%
Post-PCI 6-8-month
mm
0
0.1
0.2
0.3
0.4
0.5
2-year
EES 0.14±.41
SES 0.17±.33
Data are mean ± SEM
P=0.15
n=805 lesions
With paired angiogaphic FU
EES 0.29±.51
SES 0.31±.58
P=0.59
Late Lumen Loss to 2 YearsLate Lumen Loss to 2 Years
In a randomized clinical trial with broad inclusion criteria, EES (Xience) and SES (Cypher) provide comparable clinical outcomes out to 2 years
While there was a trend towards superior antirestenotic efficacy with EES (Xience), specifically-powered studies are needed to evaluate the clinical significance of this finding
ConclusionsConclusions
ISAR-TEST-4 Deutsches Herzzentrum, Munich. Germany
Thank YouThank You