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CYP2C19*2 and *17 Alleles Have a Significant Impact on Platelet Response and Bleeding Risk in Patients Treated With Prasugrel After Acute Coronary Syndrome.


JACC Cardiovasc Interv. 2012 Dec;5(12):1280-7


Authors: Cuisset T, Loosveld M, Morange PE, Quilici J, Moro PJ, Saut N, Gaborit B, Castelli C, Beguin S, Grosdidier C, Fourcade L, Bonnet JL, Alessi MC


Abstract

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.

PMID: 23257377 [PubMed - in process]