Association of Cytochrome P450 2C19 Genotype With the Antiplatelet Effect and Clinical Efficacy of Clopidogrel Therapy

To identify gene variants that influence clopidogrel response. DESIGN, SETTING, AND PARTICIPANTS: In the Pharmacogenomics of Antiplatelet Intervention (PAPI) Study (2006-2008), we administered clopidogrel for 7 days to 429 healthy Amish persons and measured response by ex vivo platelet aggregometry. A genome-wide association study was performed followed by genotyping the loss-of-function cytochrome P450 (CYP) 2C19*2 variant (rs4244285). Findings in the PAPI Study were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascular outcomes in an independent sample of 227 patients undergoing percutaneous coronary intervention. MAIN OUTCOME MEASURE: ADP-stimulated platelet aggregation in response to clopidogrel treatment and cardiovascular events.

Platelet response to clopidogrel was highly heritable (h(2) = 0.73; P