2020 年第 9 期 第 15 卷

CYP2C19失功能等位基因与急性冠状动脉综合征经皮冠状动脉介入术后患者主要不良心脑血管事件和出血风险的相关性研究

Correlation between CYP2C19 loss of function allele and the major adverse cardiovascular and cerebrovascular events and bleeding risk of clopidogrel in patients with acute coronary syndrome after percutaneous coronary intervention

作者：石秀锦1张翼2陈曦2彭文星1徐晓宇1李骁1井浣雨1林阳1

英文作者：Shi Xiujin1 Zhang Yi2 Chen Xi2 Peng Wenxing1 Xu Xiaoyu1 Li Xiao1 Jing Huanyu1 Lin Yang1 

单位：1首都医科大学附属北京安贞医院药事部100029；2首都医科大学化学生物与药学院临床药学系100069

英文单位：1Department of Pharmacy Beijing Anzhen Hospital Capital Medical University Beijing 100029 China; 2Clinical Pharmacology School of Chemical Biology and Pharmaceutical Science Capital Medical University Beijing 100069 China 

关键词：急性冠状动脉综合征；氯吡格雷；CYP2C19；基因多态性；主要不良心脑血管事件

英文关键词：Acutecoronarysyndrome；Clopidogrel;CYP2C19;Genepolymorphism;Majoradversecardiovascularandcerebrovasculaevents 

• 摘要：

• 目的 探索CYP2C19失功能等位基因与急性冠状动脉综合征经皮冠状动脉介入（PCI）术后应用氯吡格雷抗血小板治疗患者主要不良心脑血管事件和出血风险的相关性。方法 研究设计为回顾性队列研究。筛选并纳入2015年7月至2016年3月于首都医科大学附属北京安贞医院诊断为急性冠状动脉综合征并且成功接受PCI术的患者826例，根据患者是否携带失功能等位基因CYP2C19*2、*3分为携带失功能等位基因组和未携带失功能等位基因组，收集患者出院1年后的随访数据，对主要不良心脑血管事件及出血事件的发生进行评估。结果 826例患者中478例纳入携带失功能等位基因组，348例纳入未携带失功能等位基因组。Cox多元回归模型分析结果提示，与未携带失功能等位基因组相比，携带失功能等位基因组的主要不良心脑血管事件发生风险升高270%（风险比=3.702，95%置信区间：1.076～12.735，P=0.038）。在出血风险方面，携带失功能等位基因仅能降低小出血发生风险（风险比=0.655，95%置信区间：0.435～0.986，P=0.043），对于大出血则无影响（风险比=1.032，95%置信区间：0.228～4.664，P=0.967）。结论 携带CYP2C19失功能等位基因的急性冠状动脉综合征患者PCI术后使用氯吡格雷抗血小板治疗具有更高的主要不良心脑血管事件的发生风险和更低的小出血风险。

• Objective To explore the correlation between the inactive allele of CYP2C19 and the adverse cardiovascular and cerebrovascula events and bleeding risk of clopidogrel in patients with acute coronary syndrome after percutaneous coronary intervention(PCI). Methods Totally 826 patients who were diagnosed of acute coronary syndrome in Beijing Anzhen Hospital, Capital Medical University from July 2015 to March 2016 were screened and included. They were divided into loss of function alleles group and non loss of function alleles group.  Results Among 826 patients, 478 cases were with dysfunctional alleles and 348 cases were without dysfunctional alleles. The results of Cox multiple regression model showed that the risk of major adverse cardiovascular and cerebrovascular events was 270% higher in patients with dysfunctional alleles than that in patients without dysfunctional alleles (hazard ratio=3.702, 95% confidence interval: 1.076-12.735, P=0.038). Carrying the dysfunctional allele can only reduce the risk of small bleeding (hazard ratio=0.655, 95% confidence interval: 0.435-0.986, P=0.043), but it showed no effect on large bleeding (hazard ratio=1.032, 95% confidence interval: 0.228-4.664, P=0.967). Conclusion There is a higher incidence of major adverse cardiovascular and cerebrovascular events and a lower rate of small bleeding after PCI with clopidogrel antiplatelet therapy in patients with acute coronary syndrome with CYP2C19 dysfunctional allele.