Prospective, Randomized Trial of Paclitaxel- versus Sirolimus-Eluting Stents for Treatment of

Coronary Restenosis in Sirolimus-Eluting Stents

Robert A. Byrne, Julinda Mehilli, Klaus Tiroch, Stefanie Schulz, Steffen Massberg, Karl-Ludwig

Laugwitz, Albert Schömig, Adnan Kastrati

Deutsches Herzzentrum & 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität, Munich. Germany

ISAR-DESIRE 2

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Background

• The widespread adoption of DES therapy has led to significant absolute numbers of patients presenting with DES-restenosis

• It is estimated that up to 200,000 cases per annum occur in USA

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Background

• The optimal treatment strategy for in-stent restenosis is based on the axiom: maximize acute gain minimize late loss

ISAR-DESIRE JAMA 2005; RIBS-II JACC 2006TAXUS-V-ISR JAMA 2006; SISR JAMA 2006

• In BMS-restenosis this has most effectively been accomplished by DES

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Background

• In DES-restenosis the most effective management strategy is unclear

• While repeat DES implantation seems preferable, optimal stent type is not known Different DES (“hetero-DES”) Same DES (“homo-DES”)

Lee et al. AJC 2006; Cosgrave et al. AHJ 2007 Garg et al. CCI 2007; Byrne et al. Rev Esp Card 2008

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Background

• SES have proven superior to PES in subsets of patients with high-risk features

• The comparative performance of both stents in SES treatment failure is not known

ISAR-DESIRE JAMA 2005; ISAR-DIABETES NEJM 2005 SIRTAX NEJM 2005; ISAR-SMART-3 EHJ 2006; Schömig et al. JACC 2007

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Study Objective

• To compare the anti-restenotic efficacy of SES (Cypher) versus PES (Taxus) in patients with SES-restenosis

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Study Organization

450 patients enrolled at two centres in Munich, Germany

Angiographic follow-up at 6-8 months (84.8%)

Clinical follow-up at 12 months

Clinical follow-up at 12 months

Angiographic follow-up at 6-8 months (84.9%)

SES (Cypher)n = 225

PES (Taxus)n = 225

Design

• DESIGN: Randomized, open-label, active-control trial

• INCLUSION CRITERIA: 1. In-SES restenosis > 50%2. Symptoms/signs of ischaemia

• EXCLUSION CRITERIA: 1. Cardiogenic shock2. Lesion in LMCA or graft3. Acute myocardial infarction

• PRIMARY ENDPOINT: In-stent late loss

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Baseline Characteristics

SESn = 225

PESn = 225

Age (years) 66.4 67.1

Female 20.8 25.7

Diabetes mellitus 38.2 33.8

Clinical presentation

Stable 80.0 83.3

ACS 20.0 16.7

Patients

Numbers shown are percentages

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Baseline Characteristics

SES n = 243

PESn = 240

Vessel size 2.78±.47 2.75±.48

Lesion length 12.7±8.3 12.5±7.7

Initial SES

Cypher 38.7 38.3

ISAR stent 61.3 61.7

Lesions

Numbers shown are mean±SD or percentages

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Baseline Characteristics

SES n = 243

(%)

PESn = 240

(%)

Focal margin 21.0 18.8

Focal body 37.5 34.6

Multifocal 6.6 7.5

Diffuse/proliferative 30.0 35.8

Occlusive 4.9 3.3

Lesions – Restenosis Morphology

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30-Day Results

SES n = 225

PESn = 225

Death 0 0.4

Myocardial infarction 1.3 1.8

TLR 0 0

Death/MI/TLR 1.3 1.8

Stent thrombosis 0 0Numbers shown are percentages; P = ns for all comparisons

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0.40 0.38

0.0

0.3

0.6

0.9

Late loss, in-stent

SES PES

Primary Endpoint

P = 0.75

Late Luminal Loss

mm

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Secondary EndpointBinary Restenosis

19.020.6

0

10

20

30

40

Restenosis, in-segment

SES PES

P = 0.69%

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Secondary EndpointTLR

0

10

20

30

40

50

0 2 4 6 8 10 12

rate

, %

months

SES 16.6%SES 16.6%

PES 14.6%PES 14.6%

P P = 0.52= 0.52

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Death, MI or Stent Thrombosisra

te, %

months

0

10

20

30

40

50

0 2 4 6 8 10 12

SES 6.1%SES 6.1%

P P = 0.98= 0.98

Safety Endpoint

PES 6.3%PES 6.3%

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Death, MI or TLRra

te, %

months

0

10

20

30

40

50

0 2 4 6 8 10 12

Major Adverse Cardiac Events

P P = 0.71= 0.71

SES 20.4%SES 20.4%

PES 19.6%PES 19.6%

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Conclusions

• Repeat DES implantation for DES-restenosis is safe out to 1 year

• In cases of SES-restenosis, both SES and PES are associated with a comparable degree of anti-restenotic efficacy

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0.40

0.230.190.21

0.0

0.3

0.6

DESIRE DIABETES SMART-3 DESIRE-2

Late Luminal Loss

mm

SES (Cypher) Efficacy

ISAR-DESIRE JAMA 2005; ISAR-DIABETES NEJM 2005 ISAR-SMART-3 EHJ 2006

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Conclusions

• Drug resistance at an individual patient level may play a contributory role in the somewhat lower anti-restenotic efficacy of SES in this study

Thank You

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