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 whoseCYP2C19genotypes 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 theCYP2C19loss-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 theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62).

Conclusions:Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.

背景：日本人群经皮冠状动脉介入治疗 (PCI) 后接受氯吡格雷或普拉格雷治疗的患者的细胞色素 P450 (CYP) 2C19 基因型与不良事件之间的关联尚不清楚。

方法和结果：本研究包括 1,580名在滋贺医科大学医院评估CYP2C19基因型的患者，并对接受 PCI 后随访超过 1 年的 193 名氯吡格雷治疗患者和 217 名普拉格雷治疗患者进行了分析。在 1,580 名患者中，正常、中度和慢代谢者的患病率分别为 32%、49% 和 17%。氯吡格雷组和普拉格雷组的主要结局（定义为心血管死亡、心肌梗死、明确支架血栓形成、缺血性卒中或大出血的复合）的总体发生率没有显着差异（调整后的风险比 [HR] 1.98，95% 置信度）间隔 [CI] 0.85–4.61，P=0.12）。在CYP2C19患者中功能丧失 (LOF) 等位基因，然而，氯吡格雷组的主要结局发生率显着更高（调整后的 HR 3.19，95% CI 1.10-9.24，P=0.03），而在没有功能障碍的患者中没有观察到差异。在CYP2C19 LOF等位基因（调整的HR 0.67; 95％CI 0.14-3.26，P = 0.62）。

结论：在具有CYP2C19 LOF 等位基因的患者中，使用氯吡格雷与不良事件增加显着相关。因此，需要进一步研究以确定CYP2C19基因分型的实际应用。