Author + information
- Received July 12, 2012
- Revision received August 30, 2012
- Accepted September 28, 2012
- Published online February 1, 2013.
- Mathieu Kerneis, MD⁎,
- Johanne Silvain, MD, PhD⁎,
- Jérémie Abtan, MD⁎,
- Guillaume Cayla, MD, PhD⁎,†,
- Stephen A. O'Connor, MBBCh⁎,
- Olivier Barthélémy, MD⁎,
- Jean-Baptiste Vignalou, MD⁎,
- Farzin Beygui, MD, PhD⁎,
- Delphine Brugier, PhD⁎,
- Réjane Martin, BCh⁎,
- Jean-Philippe Collet, MD, PhD⁎ and
- Gilles Montalescot, MD, PhD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Gilles Montalescot, Bureau 236, Institut de Cardiologie, Pitié-Salpêtrière University Hospital, 47-83 bld de l'Hôpital, 75013 Paris, France
Objectives This study sought to assess the consequences of switching prasugrel to clopidogrel on platelet inhibition and clinical outcomes after an acute coronary syndrome (ACS).
Background Many ACS patients are switched from prasugrel to clopidogrel within the recommended 1-year duration of treatment.
Methods Platelet reactivity was measured with the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) in 300 ACS patients treated for 15 days with prasugrel 10 mg. Patients displaying low on-treatment platelet reactivity (LPR) and/or at high risk of bleeding were switched to clopidogrel 75 mg and tested again 15 days later. The rate of patients with high on-treatment platelet reactivity (HPR), P2Y12 reaction units (PRU) >208, and LPR (PRU <0) were evaluated before and after the switch. Bleeding and ischemic events were also recorded.
Results On a regimen of prasugrel 10 mg, the rate of patients with LPR was 45.6% (n = 137), whereas 4.3% (n = 13) had HPR. A group of 31 patients (10.3%) was switched to clopidogrel 75 mg, of whom 29 had LPR (93.5%) on a regimen of prasugrel. On-treatment platelet reactivity (PRU) increased from 14 ± 4 on a regimen of prasugrel to 155 ±15 on a regimen of clopidogrel (p = 0.0001), resulting in a much lower rate of patients with LPR (9.7%). The rate of patients with HPR increased from 0% with prasugrel to 29% (n = 9) with clopidogrel. The rate of minor bleeding decreased after the switch from 32.2% to 9.7%; p = 0.03.
Conclusions An LPR is frequent in patients treated with prasugrel 10 mg. Early switching from prasugrel 10 mg to clopidogrel 75 mg reduces the number of patients with LPR and minor bleeding events but unmasks a group of nonresponders to clopidogrel with unknown consequences on clinical outcomes.
This study was supported by the Allies in Cardiovascular Trials Initiatives and Organized Networks Group. Dr. Kerneis has received research grants from Fédération Francaise de Cardiologie. Dr. Silvain has received research grants from Sanofi-Aventis, Daiichi-Sankyo, Eli Lilly, Brahms, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; consultant fees from Daiichi-Sankyo and Eli Lilly; and lecture fees from AstraZeneca, Daiichi-Sankyo, Eli Lilly, Iroko Cardio, and Servier. Dr. Abtan has received research grants from FERCM. Dr. O'Connor has received research grants from Menarini and the European Society of Cardiology. Dr. Cayla has received a research grant from Fédération Française de Cardiologie; consultant fees from Abbott Vascular, AstraZeneca, CLS Behring, Daiichi Sankyo, and Eli Lilly; and lecture fees from Abbott Vascular, AstraZeneca, Biotronik, CLS Behring, Daiichi Sankyo, Eli Lilly, and Iroko Cardio. Dr. Beygui has received lecture fees from Roche, Sanofi-Aventis, Pfizer, and Astellas. Dr. Collet has received research grants from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Centocor, Fondation de France, INSERM, Fédération Française de Cardiologie, and Société Française de Cardiologie; consulting fees from Sanofi-Aventis, Eli Lilly, and Bristol-Myers Squibb; and lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly. Dr. Montalescot reports research grants to the institution or consulting/lecture fees from Abbott Vascular, Asante, AstraZeneca, Atrium, Bayer, Biotronik, BMS, Boehringer-Ingelheim, Boston Scientific, Choice Pharma, Brahms, CCS, CHUV, Cordis, Daiichi-Sankyo, Duke Institute, Eli Lilly, Europa, EuroRSCG, Fédération Française de Cardiologie, Fondation de France, GLG, GlaxoSmithKline, HUG, Indegene, INSERM, Institut de France, Iroko, Lead-up, Medtronic, McKinsey, MSD, Nanospheres, Navigant, Novartis, Pfizer, Portola, Roche, Royal College Physicians, Sanofi-Aventis, Stentys, SGAM, Société Française de Cardiologie, Springer, Thrombosis Research Institute, The Medicines Company, TIMI group, United States Zurich, WebMD, and Wolters. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received July 12, 2012.
- Revision received August 30, 2012.
- Accepted September 28, 2012.
- American College of Cardiology Foundation