Pharmacogenetic study of CYP2C19 variation and clopidogrel dose adjustment according to platelet reactivity monitoring in atherothromboticrisk patients in Thailand

Abstract

This study was designed to determine the effect of CYP2C19 polymorphisms on platelet response in patients with atherothrombotic-risks receiving clopidogrel treatment. Ninety-five antiplatelet naïve atherothrombotic-risk patients were enrolled consecutively. Clopidogrel at 75 mg/day was administered for 2 weeks, followed by a platelet function test (PFT). Non-responders were identified and randomized for receiving either 75 mg or 150 mg of clopidogrel for a further 2 weeks. Twenty-four subjects were non-responders with 75 mg/day, which correlated with poor metabolizer (PM) status (OR 5.69; 1.41-23.03, p = 0.015). However, the mean maximal platelet aggregation (MPA) in the 2nd test was significantly lower in the extensive metabolizers (EM) when compared to the intermediate metabolizers (IM) and PM (23.6 vs 28.1 vs 39.7; p = 0.0001). After randomizing to either 75mg or 150 mg of clopidogrel, no patient had an improved platelet response of more than 30%. However, after administering 150 mg of clopidogrel, MPA reduction (ΔMPA) was significantly greater in IM and PM when compared to that in EM (absolute ΔMPA 20.22% vs 2.6%, p 0.014; relative ΔMPA 45.07% vs 5.27%, p = 0.037). We report here the first pharmacogenetics study of clopidogrel response and show that the common CYP2C19 variants are an important determinant of ADP-stimulated platelet aggregation in Thailand. CYP2C19 genotype may be beneficial in assisting clinicians select the appropriate effective antiplatelet therapy and optimal dose for a given individual. These results collectively inform the emerging field of public health pharmacogenomics with attention to progress in the Asia-Pacific. © 2013 Bentham Science Publishers.