- 作者：Thomas Cuisset ; MD ; PhD? ; &dagger ; ; &Dagger ; ; thomas.cuisset@ap-hm.fr ; Marie Loosveld ; MD&dagger ; ; &Dagger ; ; § ; ; Pierre Emmanuel Morange ; MD ; PhD&dagger ; ; &Dagger ; ; § ; ; Jacques Quilici ; MD? ; &dagger ; ; Pierre Julien Moro ; MD? ; &Dagger ; ; Noé ; mie Saut ; PhD&dagger ; ; &Dagger ; ; Bé ; né ; dicte Gaborit ; MD&dagger ; ; &Dagger ; ; Christel Castelli ; PhD¡Î ; Shirley Beguin ; PhD¶ ; ; Charlotte Grosdidier ; MD&dagger ; ; &Dagger ; ; § ; ; Laurent Fourcade ; MD# ; Jean-Louis Bonnet ; MD? ; &dagger ; ; &Dagger ; ; Marie-Christine Alessi ; MD ; PhD&dagger ; ; &Dagger ; ; § ;
- 关键词：acute coronary syndrome ; bleeding ; genotyping ; platelet testing ; prasugrel
- 刊名：JACC: Cardiovascular Interventions
- 出版年：2012
- 出版时间：December, 2012
- 年：2012
- 卷：5
- 期：12
- 页码：1280-1287
- 全文大小：1044 K
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 ¡À 15 % vs. 27 ¡À 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 ¡À 13 % vs. 31 ¡À 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.