Comparison between Clopidogrel and Prasugrel Associated with CYP2C19 Genotypes in Patients Receiving Percutaneous Coronary Intervention in a Japanese Population

Abstract

Background: The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear. Methods and Results: This study consisted of 1,580 patients whose CYP2C19 genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85–4.61, P=0.12). Among patients with the CYP2C19 loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10–9.24, P=0.03), whereas no difference was observed among patients without the CYP2C19 LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62). Conclusions: Among patients with the CYP2C19 LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use of CYP2C19 genotyping.