Author + information
- Received June 4, 2012
- Revision received July 10, 2012
- Accepted July 19, 2012
- Published online December 1, 2012.
- Thomas Cuisset, MD, PhD⁎,†,‡,⁎ (, )
- Marie Loosveld, MD†,‡,§,
- Pierre Emmanuel Morange, MD, PhD†,‡,§,
- Jacques Quilici, MD⁎,†,
- Pierre Julien Moro, MD⁎,‡,
- Noémie Saut, PhD†,‡,
- Bénédicte Gaborit, MD†,‡,
- Christel Castelli, PhD∥,
- Shirley Beguin, PhD¶,
- Charlotte Grosdidier, MD†,‡,§,
- Laurent Fourcade, MD#,
- Jean-Louis Bonnet, MD⁎,†,‡ and
- Marie-Christine Alessi, MD, PhD†,‡,§
- ↵⁎Reprint requests and correspondence:
Dr. Thomas Cuisset, Aix-Marseille Université, Faculté de Médecine, Dèpartement de Cardiologie, CHU Timone, 264 rue Saint Pierre, F-13385 Marseille, France
Objectives The present study was designed to assess the effect of genetic variants on chronic biological response to prasugrel and bleeding complications.
Background CYP2C19*2 loss-of-function allele and CYP2C19*17 gain-of-function allele have been linked with response to clopidogrel, but preliminary data did not show any significant influence of these alleles on prasugrel effect.
Methods A total of 213 patients undergoing successful coronary stenting for acute coronary syndrome and discharged with prasugrel 10 mg daily were included. Prasugrel response was assessed at 1 month with the platelet reactivity index (PRI) vasodilator-stimulated phosphoprotein (VASP) and high on-treatment platelet reactivity (HTPR) defined as PRI VASP > 50% and hyper-response as PRI VASP <75th percentile (PRI VASP < 17%). CYP2C19*2 and CYP2C19*17 genotyping were performed.
Results Carriers of loss-of-function *2 allele had significantly higher PRI VASP than noncarriers (33 ± 15% vs. 27 ± 14%, p = 0.03) and higher rate of HTPR (16% vs. 4%, p = 0.01). Conversely, carriers of *17 gain-of-function allele had significantly lower PRI VASP than noncarriers (25 ± 13% vs. 31 ± 15%, p = 0.03, p = 0.03), lower rate of HTPR (1% vs. 10%, p = 0.02), higher rate of hyper-response (34% vs. 21%, p = 0.02), and higher rate of bleeding complications than noncarriers: 23% versus 11%, (odds ratio [95% confidence interval]: 2.5 [1.2 to 5.4]; p = 0.02). No significant influence of genotypes on platelet reactivity assessed by adenosine diphosphate–induced platelet aggregation was observed.
Conclusions The present study shows a significant influence of CYP2C19*2 and *17 alleles on response to chronic treatment by prasugrel 10 mg daily and occurrence of bleeding complications.
Dr. Cuisset has received consultant fees from Daiichi-Sankyo and Eli Lilly, and lecture fees from AstraZeneca, Abbott Vascular, Biotronik, Boston Scientific, Cordis, Daiichi-Sankyo, Edwards, Eli Lilly, Sanofi-Aventis, and Servier. Dr. Alessi has been a regional board member of Eli Lilly and received research funding from Sanofi-Aventis. The other authors have stated that they have no relationships relevant to the contents of this paper to disclose.
- Received June 4, 2012.
- Revision received July 10, 2012.
- Accepted July 19, 2012.
- American College of Cardiology Foundation