The aim of this study was to investigate the association between CYP2C19 gene polymorphisms and the risk of cardiovascular events in the early stage and subsequent period after percutaneous coronary intervention (PCI) among patients who received clopidogrel. Between October 2015 and January 2017, CYP2C19 genotyped patients who were treated with clopidogrel after PCI were enrolled in this study. Included patients were categorized as non–loss-of-function metabolizers, intermediate metabolizers, and poor metabolizers based on CYP2C19 genotype. The primary outcome was a composite of any-cause mortality, nonfatal myocardial infarction, nonfatal ischemic stroke, and stent thrombosis occurring during exposure to clopidogrel. The rates of clinical outcome events were compared between CYP2C19 phenotypes. Landmark analyses were processed at 90 days and 1 year post-PCI. Of 1341 patients, 161 (12.0%) had 2 copies of loss-of-function (LOF) alleles, 621(46.3%) had one LOF allele, and 559 (41.7%) had no LOF allele. At the 3-month follow-up, the primary outcome events were more frequent in carriers of 2 LOF alleles (5.6%) than in noncarriers (1.8%) [adjusted hazard ratio (HR) 2.944, 95% confidence interval, 1.184–7.321, P = 0.020). A similar finding was observed among in patients with acute coronary syndrome indications at the index PCI (adjusted HR 3.046, 95% confidence interval, 1.237–7.501, P = 0.015). These differences did not persist within the subsequent 9 months of follow-up, among either all comers or subjects with acute coronary syndrome. In conclusion, these data demonstrate a higher risk for ischemic events in patients with 2 CYP2C19 LOF alleles who are prescribed clopidogrel, seen at 3 months after PCI, that is not sustained for 12 months.

本研究的目的是调查接受氯吡格雷的患者中，CYP2C19 基因多态性与经皮冠状动脉介入治疗（PCI）后早期和后期心血管事件风险之间的关系。2015 年 10 月至 2017 年 1 月，本研究招募了 PCI 后接受氯吡格雷治疗的 CYP2C19 基因型患者。纳入的患者根据 CYP2C19 基因型分为非功能丧失代谢者、中间代谢者和不良代谢者。主要结局是氯吡格雷暴露期间发生的全因死亡率、非致死性心肌梗死、非致死性缺血性卒中和支架血栓形成的复合结果. 在 CYP2C19 表型之间比较临床结果事件的发生率。标志性分析在 PCI 后 90 天和 1 年进行处理。在 1341 名患者中，161 名（12.0%）有 2 个功能丧失（LOF）等位基因，621 名（46.3%）有一个 LOF 等位基因，559 名（41.7%）没有 LOF 等位基因。在 3 个月的随访中，2 个 LOF 等位基因的携带者 (5.6%) 的主要结局事件比非携带者 (1.8%) 更频繁[调整后的风险比 (HR) 2.944, 95% 置信区间, 1.184–7.321 , P = 0.020)。在有急性冠状动脉综合征适应症的患者中观察到类似的发现（调整后的 HR 3.046，95% 置信区间，1.237-7.501，P= 0.015)。在随后的 9 个月的随访中，这些差异在所有参与者或患有急性冠状动脉综合征的受试者中都没有持续存在。总之，这些数据表明，在 PCI 后 3 个月观察到的 2 个 CYP2C19 LOF 等位基因患者使用氯吡格雷时发生缺血事件的风险更高，且未持续 12 个月。