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

https://doi.org/10.1016/j.jcin.2012.07.015Get rights and content
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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.

Key Words

acute coronary syndrome
bleeding
genotyping
platelet testing
prasugrel

Abbreviations and Acronyms

ACS
acute coronary syndrome
ADP
adenosine diphosphate
ADP-Ag
adenosine diphosphate–induced platelet aggregation
BARC
Bleeding Academic Research Consortium
CI
confidence interval
CYP
cytochrome P450
HTPR
high on-treatment platelet reactivity
LTA
light transmittance aggregometry
OR
odds ratio
MFI
median fluorescence intensity
PCI
percutaneous coronary interventions
PCR
polymerase chain reaction
PGE1
prostaglandin E1
PRI
platelet reactivity index
TIMI
Thrombolysis In Myocardial Infarction
VASP
vasodilator-stimulated phosphoprotein

Cited by (0)

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.