作者：刘苗苗，王勃，韩东建，张义，姜庆姣，王富行，庄沅松，沈德良

单位：

郑州大学第一附属医院心血管内科

单位（英文）：

Department of Cardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

关键词：

冠心病; 经皮冠状动脉介入治疗; CYP2C19基因; 血小板聚集抑制剂; 氯吡格雷; 替格瑞洛; 预后;

关键词（英文）：

Coronary disease; Percutaneous coronary intervention; CYP2C19 gene; Platelet aggregation inhibitors;Clopidogrel; Ticagrelor; Prognosis

中图分类号：

DOI：

10.12114/j.issn.1008-5971.2023.00.096

基金项目：

摘要：

目的 探讨CYP2C19基因检测在冠心病患者PCI后抗血小板药物治疗中的指导价值。方法 回顾性收集2016—2018年于郑州大学第一附属医院行PCI的冠心病患者588例为研究对象。患者术前均行CYP2C19基因检测，根据CYP2C19基因检测结果将其分为中慢代谢与快代谢。PCI后快代谢患者根据其意愿服用氯吡格雷或替格瑞洛，中慢代谢患者建议服用替格瑞洛，对于替格瑞洛不良反应较大者服用氯吡格雷。随访39～76个月，随访截至2022年4月。主要终点为发生主要不良心脑血管事件(MACCE)，次要终点为发生出血事件。使用Kaplan-Meier法绘制生存曲线并进行Log-rank检验；采用多因素Cox比例风险回归分析探讨中慢代谢患者发生终点事件的影响因素。结果588例患者根据CYP2C19基因检测结果分为中慢代谢387例，快代谢201例。中慢代谢者根据治疗方法分为中慢代谢氯吡格雷组(n=124)和中慢代谢替格瑞洛组(n=263)，快代谢者根据治疗方法分为快代谢氯吡格雷组(n=78)和快代谢替格瑞洛组(n=123)。中慢代谢氯吡格雷组与中慢代谢替格瑞洛组累积MACCE发生率比较，差异有统计学意义(χ2=5.419,P=0.020)；中慢代谢氯吡格雷组与中慢代谢替格瑞洛组累积出血事件发生率比较，差异无统计学意义(χ2=0.001,P=0.979)。快代谢氯吡格雷组与快代谢替格瑞洛组累积MACCE、出血事件发生率比较，差异无统计学意义(χ2=0.508,P=0.476；χ2=0.081,P=0.776)。多因素Cox比例风险回归分析结果显示，应用氯吡格雷[HR=1.680,95%CI(1.022,2.764),P=0.041]是中慢代谢患者发生MACCE的独立影响因素；年龄[HR=1.029,95%CI(1.000,1.058),P=0.049]是中慢代谢患者发生出血事件的独立影响因素。结论 与PCI后应用替格瑞洛相比，PCI后应用氯吡格雷的中慢代谢冠心病患者远期发生MACCE的概率较高，应用氯吡格雷是中慢代谢患者发生MACCE的危险因素，CYP2C19基因检测可指导冠心病患者在PCI后抗血小板药物治疗中做出更佳选择。

英文摘要：

　Objective To investigate the guiding value of CYP2C19 gene testing in antiplatelet drug therapy inpatients with coronary artery disease after PCI. Methods A total of 588 patients with coronary artery disease who underwent PCIin the First Affiliated Hospital of Zhengzhou University from 2016 to 2018 were retrospectively collected as study subjects. Allpatients underwent CYP2C19 gene detection testing before surgery, and they were divided into medium and slow metabolic and fastmetabolic according to the results of CYP2C19 gene testing. Patients with fast metabolic after PCI were advised to take clopidogrelor ticagrelor according to their wishes, patients with medium and slow metabolic were advised to take ticagrelor, and those withlarge adverse reactions to ticagrelor were advised to take clopidogrel. The follow-up period was 39 to 76 months, and the followup date up to April 2022. The primary endpoint event was major adverse cardiovascular or cerebrovascular events (MACCE) ,and the secondary endpoint event was bleeding events. Kapalan-Meier method was used to draw the survival curve and Log-ranktest was conducted. Multivariate Cox proportional risk regression analysis was used to explore the influencing factors of endpointevent in patients with medium and slow metabolic. Results The 588 patients were divided into 387 medium and slow metabolicand 201 fast metabolic according to CYP2C19 gene testing results. The medium and slow metabolic patients were divided into medium and slow metabolic clopidogrel group (n=124) and medium and slow metabolic ticagrelor group (n=263) according to thetreatment, and the fast metabolic patients were divided into fast metabolic clopidogrel group (n=78) and fast metabolic ticagrelorgroup (n=123) according to the treatment. There was statistically significant differences in the incidence of cumulative MACCEbetween medium and slow metabolic clopidogrel group and medium and slow metabolic ticagrelor group (χ2=5.419, P=0.020) ;there was no statistically significant difference in the incidence of cumulative bleeding events between medium and slow metabolicclopidogrel group and medium and slow metabolic ticagrelor group (χ2=0.001, P=0.979) . There was no statistically significantdifference in the incidence of cumulative MACCE and bleeding events between fast metabolic clopidogrel group and fast metabolicticagrelor group (χ2=0.508, P=0.476; χ2=0.081, P=0.776) . Multivariate Cox proportional risk regression analysis showed thatthe clopidogrel was the independent influencing factor of MACCE in patients with medium and slow metabolic [HR=1.680, 95%CI(1.022, 2.764) , P=0.041] ; age was the independent influencing factors of bleeding events in patients with medium and slowmetabolic [HR=1.029, 95%CI (1.000, 1.058) , P=0.049] . Conclusion Compared with taking ticagtelor after PCI, patients withcoronary heart disease with medium and slow metabolic taking clopidogrel after PCI have higher long-term probability of MACCE,clopidogrel is the risk factor of MACCE in patients with medium and slow metabolic. CYP2C19 gene testing can guide patientswith coronary artery to make better choice for antiplatelet drug therapy after PCI.

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