Author + information
- Received November 19, 2014
- Revision received February 21, 2015
- Accepted February 23, 2015
- Published online April 28, 2015.
- Katrin A. Fiedler, MD∗,
- Michael Maeng, MD†,
- Julinda Mehilli, MD‡,§,
- Stefanie Schulz-Schüpke, MD∗,
- Robert A. Byrne, MB, BCh, PhD∗,§,
- Dirk Sibbing, MD‡,§,
- Petra Hoppmann, MD‖,
- Simon Schneider, MD‖,
- Massimiliano Fusaro, MD∗,
- Ilka Ott, MD∗,
- Steen D. Kristensen, MD†,
- Tareq Ibrahim, MD‖,
- Steffen Massberg, MD‡,§,
- Heribert Schunkert, MD∗,§,
- Karl-Ludwig Laugwitz, MD§,‖,
- Adnan Kastrati, MD∗,§ and
- Nikolaus Sarafoff, MD‡∗ ()
- ∗Deutsches Herzzentrum München, Technische Universität, Klinik für Herz- und Kreislauferkrankungen, Munich, Germany
- †Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
- ‡Klinikum der Universität München, Ludwig-Maximilians Universität, Medizinische Klinik und Poliklinik I, Munich, Germany
- §Deutsches Zentrum für Herz Kreislaufforschung, partner site Munich Heart Alliance, Munich, Germany
- ‖Klinikum rechts der Isar, Technische Universität, I. Medizinische Klinik und Poliklinik, Munich, Germany
- ↵∗Reprint requests and correspondence:
Dr. Nikolaus Sarafoff, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig Maximilians Universität München, Marchioninistrasse 15, 81377 München, Germany.
Background Patients receiving oral anticoagulation (OAC) who undergo drug-eluting stent (DES) implantation require additional dual antiplatelet therapy with aspirin and clopidogrel. Such triple therapy confers an elevated bleeding risk, and its optimal duration is not known.
Objectives The goal of this study was to evaluate whether shortening the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation was associated with a superior net clinical outcome in patients receiving concomitant aspirin and OAC.
Methods In this randomized, open-label trial, we enrolled patients receiving OAC who underwent DES implantation at 3 European centers between September 2008 and December 2013. A total of 614 patients receiving concomitant aspirin and OAC were randomized to either 6-week clopidogrel therapy (n = 307) or 6-month clopidogrel therapy (n = 307). The primary endpoint was a composite of death, myocardial infarction (MI), definite stent thrombosis, stroke, or Thrombolysis In Myocardial Infarction (TIMI) major bleeding at 9 months.
Results The primary endpoint occurred in 30 patients (9.8%) in the 6-week group compared with 27 patients (8.8%) in the 6-month group (hazard ratio [HR]: 1.14; 95% CI: 0.68 to 1.91; p = 0.63). There were no significant differences for the secondary combined ischemic endpoint of cardiac death, MI, definite stent thrombosis, and ischemic stroke (12 [4.0%] vs. 13 [4.3%]; HR: 0.93; 95% CI: 0.43 to 2.05; p = 0.87) or the secondary bleeding endpoint of TIMI major bleeding (16 [5.3%] vs. 12 [4.0%]; HR: 1.35; 95% CI: 0.64 to 2.84; p = 0.44).
Conclusions Six weeks of triple therapy was not superior to 6 months with respect to net clinical outcomes. These results suggest that physicians should weigh the trade-off between ischemic and bleeding risk when choosing the shorter or longer duration of triple therapy. (Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation [ISAR-TRIPLE]; NCT00776633)
The study sponsor was Deutsches Herzzentrum München. The study was supported in part by an unrestricted research grant from Abbott, Deutsches Herzzentrum München, and PCI Research at Aarhus University Hospital. Neither the sponsor nor the research grant providers had any role in study design, data collection, data analysis, data interpretation, or writing of the report, and they did not review or comment on this report. Dr. Mehilli has received fees for lectures and advisory boards from Abbot Vascular, Terumo, and Lilly/Daiichi-Sankyo. Dr. Sibbing has received speaker fees and honoraria for consulting from Eli Lilly, Daiichi-Sankyo, Bayer Vital, AstraZeneca, Verum Diagnostica, and Roche Diagnostics; and research grants from Roche Diagnostics. Dr. Byrne has received lecture fees from B. Braun and Biotronik. Dr. Schneider has received fees for lectures, advisory boards, or traveling from Abbott Vascular and Medtronic. Dr. Kristensen has received lecture fees from AstraZeneca, Eli-Lilly, Sanofi, and The Medicines Company. Dr. Schunkert has received fees for lectures, advisory boards or traveling from AstraZeneca, SERVIER, Boehringer-Ingelheim, MSD Sharp & Dohme, and Berlin-Chemie. Dr. Kastrati has received payments for lectures or event adjudication activity from Abbott, AstraZeneca, Biosensors, Biotronik, Daiichi-Sankyo, MSD, and The Medicines Company; and also holds patents related to stent technology. Dr. Sarafoff has reported fees for lectures or traveling from Lilly/Daiichi-Sankyo, Boehringer Ingelheim, Bayer Healthcare, Boston Scientific, Biotronik, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 19, 2014.
- Revision received February 21, 2015.
- Accepted February 23, 2015.
- 2015 American College of Cardiology Foundation