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CYP2C19 Genetic Polymorphism, Rabeprazole and Esomeprazole Have no Effect on the Anti-Platelet Action of Clopidogrel.


J Cardiovasc Pharmacol. 2013 Mar 7;


Authors: El-Halabi MM, Zgheib N, Mansour NM, Malli A, Ghaith OA, Mahfouz R, Alam S, Sharara AI


Abstract

The aim of this study is to investigate the effect of CYP2C19 polymorphism and co-therapy with rabeprazole or esomeprazole on the anti-platelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and *3, and vasodilator stimulated phosphoprotein (VASP) testing to measure platelet reactivity index (PRI). 239 consecutive patients were enrolled: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). 45 patients had loss of function polymorphism (LOF) (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean platelet reactivity index (PRI) was 20.7±21.9% in the C group, 19.1±20.9% in the CR group, and 24.5±22.9% in the CE group (p= NS). High-on-treatment Platelet Reactivity (HPR), defined as PRI>50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE respectively (p=NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor PPI co-therapy were associated with HPR. The use of PPIs was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.

PMID: 23474843 [PubMed - as supplied by publisher]