CYP2C19基因检测对冠心病患者氯吡格雷治疗的临床意义

The value of CYP2C19 gene detection and clopidogrel therapy in patients with coronary heart disease

目的:观察药物代谢基因CYP2C19的基因多态性与冠心病患者氯吡格雷临床疗效的关系,探讨CYP2C19基因检测对冠心病患者抗凝治疗的临床意义。方法:选择诊断明确且进行了CYP2C19基因多态性检测的冠心病患者260例,其中PCI治疗者160例,多支病变不宜行PCI治疗又未接受冠脉旁路移植术(CABG)患者100例。CYP2C19基因检测快代谢型122例,氯吡格雷为常规75mg/d;中慢代谢型138例,其中氯吡格雷常规剂量(75mg/d)口服者86例,高剂量(150mg/d)口服者52例。对比分析3组患者院外用药情况、主要不良心脏事件(MACE)发生率、出血不良反应以及再次血运重建、再发心绞痛的发生情况。结果:(1)在药物使用方面,中慢代谢型的氯吡格雷常规剂量组硝酸酯类、血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂(ACEI/ARB)、β受体阻滞剂使用率明显高于快代谢组和中慢代谢的高剂量组;(2)MACE的发生情况,中慢代谢的常规剂量组非致死性心肌梗死发生率明显高于快代谢组和中慢代谢的高剂量组;(3)各种出血不良反应3组间比较均无明显差异;(4)中慢代谢常规剂量组再发心绞痛发生率高于快代谢组和氯吡格雷高剂量组,再次血运重建率3组间无差异;(5)多因素Logistic回归分析:CYP2C19*2基因型、高血压病史、糖尿病史是MACE发生的高危因素(OR=2.641,95%CI:1.267~5.504;OR=2.217,95%CI:1.088~4.515;OR=2.950,95%CI:1.466~5.938)。结论:CYP2C19基因多态性与PCI及多支病变冠心病患者院外再发心绞痛、非致死性心肌梗死和口服药物种类有关,CYP2C19*2是MACE发生的高危因素之一,CYP2C19基因多态性检测对临床抗血小板治疗具有指导意义。

Objective：To investigate the relationship between CYP2C19 gene polymorphism and clinical efficacy of clopidogrel in patients with coronary artery disease（CAD）.Method：A total of 260 patients with CAD was enrolled,including 160 patients with PCI and 100 patients without PCI or CABG.According to CYP2C19 gene detection,the patients were divided into 3groups.The patients who were fast metabolism received clopidogrel 75mg/day（n=122）.Patients with medium or slow metabolism were received normal dosage clopidogrel 75mg/day（n=86）or high dosage clopidogrel 150mg/day（n=52）.All patients were observed the drug use out-of-hospital,MACE incidence,bleeding condition,vascular reconstruction and recurrent angina.Result：1Usage rates of nitrates,ACEI/ARB,β-blockers were higher in medium-slow metabolism group with routine dose clopidogrel than fast metabolism group and high-dose group.2The incidence of non-fatal myocardial infarction was higher in medium-slow metabolism group with routine dose clopidogrel than fast metabolism group and high-dose group.3Bleeding condition was similar among three groups.4 The incidence of recurrent angina was higher in mediumslow metabolism group with routine dose clopidogrel than fast metabolism group and high-dose group.The occurrence of vascular reconstruction was similar among three groups.5 Multivariate logistic regression analysis showed that CYP2C19＊2genotype,hypertension and diabetes were risk factors of MACE（OR=2.641,95% CI：1.267-5.504;OR=2.217,95% CI：1.088-4.515;OR=2.950,95% CI：1.466-5.938）.Conclusion：CYP2C19gene polymorphism was associated with the incidence of recurrent angina,non-fatal myocardial infarction and drug use out-of-hospital in patients with PCI or multivessel disease.CYP2C19＊2was one of the related risk factors of MACE.CYP2C19 gene polymorphism detection is valuable to guide clinical anti-platelet therapy.