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