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

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

Coronary Restenosis in Sirolimus-Eluting Stents

Intracoronary Stenting and Angiographic Results: Drug Eluting

Stents for In-Stent Restenosis ISAR-DESIRE 2

ISAR DESIRE 2ISAR DESIRE 2

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 ischemia

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

ISAR DESIRE 2ISAR DESIRE 2

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

• PRIMARY ENDPOINT:In-stent late loss

• ASSUMPTIONS: Late loss SES = 0.60mmLate loss PES = 0.40mmPower: 90%α-level: 0.05

• SAMPLE SIZE ESTIMATION:190 patients with angiographic follow-up in each group

ISAR DESIRE 2ISAR DESIRE 2

Primary EndpointLate Luminal Loss

P = 0.75

Cum

ulat

ive

rate

, %

0

20

40

60

80

100

-2 -1 0 1 2 3 LLL, mm

PESSES

ISAR DESIRE 2ISAR DESIRE 2

Secondary EndpointBinary Restenosis

19.020.6

0

10

20

30

40

Restenosis, in-segment

SES PES

P = 0.69%

ISAR DESIRE 2ISAR DESIRE 2

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

ISAR DESIRE 2ISAR DESIRE 2

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%

ISAR DESIRE 2ISAR DESIRE 2

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%

ISAR DESIRE 2ISAR DESIRE 2

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

ISAR DESIRE 2ISAR DESIRE 2

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

ISAR DESIRE 2ISAR DESIRE 2

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