prospective, randomized trial of paclitaxel- versus sirolimus- eluting stents for treatment of...
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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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