Author + information
- Received January 27, 2015
- Revision received March 6, 2015
- Accepted March 9, 2015
- Published online July 1, 2015.
- Lorenz Räber, MD, PhD∗,
- Roland Klingenberg, MD†,
- Dik Heg, PhD‡,
- Henning Kelbæk, MD§,
- Marco Roffi, MD‖,
- David Tüller, MD¶,
- Andreas Baumbach, MD#,
- Thomas Zanchin, MD∗,
- David Carballo, MD‖,
- Miodrag Ostojic, MD, PhD∗∗,
- Giulio G. Stefanini, MD, PhD∗,
- Nicolas Rodondi, MD††,
- Clemens von Birgelen, MD, PhD‡‡,
- Aris Moschovitis, MD∗,
- Thomas Engstrøm, MD§,
- Baris Gencer, MD‖,
- Reto Auer, MD§§,
- Bernhard Meier, MD∗,
- Francois Mach, MD‖,
- Thomas F. Lüscher, MD∗,
- Peter Jüni, MD‡,‖‖,
- Christian M. Matter, MD†,
- Stephan Windecker, MD∗,‖‖∗ (, )
- COMFORTABLE and SPUM-ACS Trial Investigators
- ∗Department of Cardiology, Bern University Hospital, Bern Switzerland
- †University Heart Center, Cardiology, University Hospital, Zurich, Switzerland
- ‡Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- §Cardiac Catheterization Laboratory, Rigshospitalet, Copenhagen, Denmark
- ‖Division of Cardiology, University Hospital, Geneva, Switzerland
- ¶Cardiology Department, Triemlispital, Zurich, Switzerland
- #Bristol Heart Institute, Bristol, United Kingdom
- ∗∗Department of Cardiology, Belgrade University Hospital, Belgrade, Serbia
- ††Department of Internal Medicine, Bern University Hospital, Bern, Switzerland
- ‡‡Department of Cardiology, Thoraxcentrum Twente and University of Twente, Enschede, the Netherlands
- §§Department of Medicine, University Hospital Lausanne, Switzerland
- ‖‖Clinical Trials Unit, Department of Clinical Research, University of Bern, Bern, Switzerland
- ↵∗Reprint requests and correspondence:
Dr. Stephan Windecker, Department of Cardiology, Bern University Hospital, Freiburgstrasse, 3010 Bern, Switzerland.
Objectives The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention.
Background Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients.
Methods Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days.
Results Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36).
Conclusions This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).
The COMFORTABLE and SPUM-ACS trials were supported by a grant by the Swiss National Science Foundation (33CM30-124112 and 310030-118353). The COMFORTABLE trial was an investigator-initiated trial supported by an unrestricted grant of Biosensors S.A., Morges, Switzerland. The SPUM-ACS cohort study is an investigator-initiated study further supported by unrestricted grants of Eli Lilly, Vernier, Switzerland and AstraZeneca, Zug, Switzerland. The funding sources were not involved in the study conduct including design, site selection, data collection, analysis, and interpretation of the data. Dr. Meier has received institutional research grants from Abbott Vascular, Boston Scientific, Biosensors International, St. Jude Medical, and Cordis and has received speaker honoraria from St. Jude Medical. Dr. Klingenberg has received speaker honoraria from Eli Lilly, Bayer HealthCare, and Servier. Dr. Roffi has received institutional grants from Abbott Vascular, Medtronic, Boston Scientific, Biosensors International, and Biotronik. Dr. Baumbach has received research support from Abbott Vascular, The Medicines Company, and Biosensors International. Dr. Stefanini has received speaker honoraria from Abbott Vascular, AstraZeneca, Biosensors International, and Biotronik. Drs. Lüscher and Matter have received institutional research grants from AstraZeneca, Biosensors, Biotronik, Boston Scientific, Daiichi Sankyo, Eli Lilly, Medtronic, Merck Sharp & Dohme, and Roche. Dr. von Birgelen has received institutional research grants from Abbott Vascular, Biotronik, Boston Scientific, and Medtronic; and was a consultant for or received lecture honoraria from Abbott Vascular, Biotronik, Boston Scientific, Medtronic, and Merck Sharp & Dohme. Dr. Jüni is an unpaid steering committee or statistical executive committee member of trials funded by Abbott Vascular, Biosensors International, Medtronic, and St. Jude Medical. Dr. Windecker has received speaker honoraria from AstraZeneca, Eli Lilly, Abbott Vascular, Biotronik, Boston Scientific, and BayerHealth Care; and institutional research grants from Abbott Vascular, AstraZeneca, Boston Scientific, Biosensors International, Biotronik, Cordis, Eli Lilly, Medtronic, and St. Jude Medical, and The Medicines Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 27, 2015.
- Revision received March 6, 2015.
- Accepted March 9, 2015.
- 2015 American College of Cardiology Foundation