CYP2 C19基因多态性联合血小板功能检测指导PCI术后患者抗血小板药物选择的效果观察

目的 探讨 CYP2C19基因多态性联合血小板功能检测指导下的抗血小板药物选择对经皮冠状动脉介入术(percutaneous transluminal coronary intervention,PCI) 治疗后患者临床预后的影响。方法 选取2017 年10月至 2018年2月因冠状动脉粥样硬化性心脏病就诊并成功完成PCI的患者200例,最终纳入符合条件并完成随访的患者190例。根据基因型将患者分为氯吡格雷正常代谢型(超快代谢型和快代谢型)和异常代谢型(中间代谢型和慢代谢型)两组。根据治疗后血小板聚集率将患者分为氯吡咯雷正常反应型(clopidogrel normal reaction,NCR,最大血小板聚集率＜46)和氯吡咯雷抵抗型(clopidogrel low reaction,LCR,最大血小板聚集率≥46)。结合基因型及血小板聚集率的检测结果,将基因型为正常代谢型+氯吡咯雷正常反应型患者分为A组,正常代谢型+氯吡咯雷抵抗型或异常代谢型+氯吡咯雷正常反应型患者归为B组,异常代谢型+氯吡咯雷抵抗型患者为C组。A组及B组给予阿司匹林+氯吡格雷抗血小板治疗,C组给予阿司匹林+替格瑞洛抗血小板治疗。随访3组12个月内主要不良心血管事件及出血事件的发生率。结果 3组患者一般临床资料(性别、年龄、吸烟、饮酒、高血压、糖尿病、高脂血症),临床用药[血管紧张素受体转换酶抑制剂(angiotensin converting enzyme inhibitor,ACEI)/血管紧张素受体阻滞剂(angiotension receptor blocker,ARB)、β受体阻滞剂、钙离子拮抗剂(calcium-channel antagonist,CCB)、质子泵抑制剂、硝酸酯类药物],随访1年时常规血液生物化学指标(肌酐、尿酸、转氨酶),PCI基本特征(多支病变、支架植入数量、支架直径、支架长度)等方面,差异均无统计学意义(P均>0.05);3组总不良心血管事件(major adverse cardiovascular event, MACE)发生率差异有统计学意义(P<0.05),其中靶血管再次血运重建,C组发生率降低,主要出血事件均为0;3组呼吸困难不良反应发生率,C组较A、B两组升高,但差异无统计学意义(P>0.05)。结论 通过CYP2C19基因型联合血小板功能检测共同筛选出的氯吡咯雷低反应患者给予阿司匹林联合替格瑞洛抗血小板治疗可以降低不良心血管事件的发生,并不增加出血事件的发生率,能够改善患者的预后。

Anti-platelet strategies in patients with percutaneous coronary intervention based on CYP2C19 gene polymorphism and platelet function

Objective To investigate the role of CYP2C19 gene polymorphism and platelet function detection in the anti-platelet strategies in the clinical prognosis of patients after percutaneous coronary intervention. Methods From October 2017 to February 2018, a total of 200 with coronary heart disease undergoing percutaneous coronary intervention (PCI) were included, 190 of which were successfully followed up. According to genotype, the patients were divided into normal metabolism of clopidogrel (ultrafast and fast metabolism) and abnormal metabolism (intermediate and slow metabolism). According to the platelet aggregation rate, patients were divided into the normal clopidogrel reaction (NCR) type (maximum platelet aggregation rate<46) and the resistance type, i.e., low clopidogrel (LCR) type (maximum platelet aggregation rate≥46). Group A included normal metabolism of clopidogrel and NCR type, Group B included abnormal metabolism or abnormal clopidogrel resistance type. Group C included both abnormal types. The groups A and B were treated with aspirin and clopidogrel,while the group C were treated with aspirin and ticagrelor. Follow up the major adverse cardiovascular events and bleeding events within 12 months. Results The general clinical data (gender, age, smoking, drinking, hypertension, diabetes, hyperlipidemia), clinical medication [angiotensin converting enzyme inhibitor(ACEI) and angiotension receptor blocker(ARB), beta blockers, calcium-channel antagonist(CCB), proton pump inhibitor (PPI), nitrate medications], biochemical criterion (creatinine, uric acid, transaminase), and PCI surgery (multivessel lesions, stents of number, diameter, length) showed no statistical difference (P>0.05). The incidence of major adverse cardiac events (MACEs) and the target vessels re-revascularization had significant difference in three groups(P＜0.05). The incidence of target vessels re-revascularization in group C was decreased, with a statistically significant difference compared with group B (0 vs 11%).There were no statistically significant differences in cardiogenic death, nonfatal myocardial infarction, and recurrent angina pectoris (P>0.05). No MACEs were observed in all the groups. The incidence of dyspnea in group C was higher than that in group A and group B, without statistical significance. Conclusions Aspirin combined with ticagrelon antiplatelet therapy could reduce the incidence of adverse cardiovascular events, without increasing the incidence of bleeding events, and improve the prognosis of clopidogrel hyporeactive patients screened by CYP2C19 genotype combined with platelet function detection.