基于药物基因多态性及血栓弹力图选择抗栓治疗对缺血性脑卒中复发的影响  

Effect of antithrombotic therapy selection on stroke recurrence basedon drug gene polymorphism and thromboelastography

作　　者：宋秋英[1,2] 陶程娟 吴之昊 谢哲锋 刘海俊 陈彬彬 SONG Qiuying;TAO Chenjuan;WU Zhihao;XIE Zhefeng;LIU Haijun;CHEN Binbin(Department of Neurology,Affiliated Hospital of Hangzhou Normal University,Hangzhou 310015,Zhejiang,China;Department of Neurology,The Third People's Hospital of Deqing,Deqing 313200,Zhejiang,China;Medical Laboratory,Affiliated Hospital of Hangzhou Normal University,Hangzhou 310015,Zhejiang,China)

机构地区：[1]杭州师范大学附属医院神经内科,浙江杭州310015 [2]德清第三人民医院神经内科,浙江德清313200 [3]杭州师范大学附属医院医学检验科,浙江杭州310015

出　　处：《中国临床药理学与治疗学》2024年第9期1035-1041,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：湖州市科技局项目(2021GY70);杭州市医药卫生科技项目(A20210015);浙江省科技厅项目(2023C03094)。

摘　　要：目的:氯吡格雷和阿司匹林是脑血管病二级预防的常用药物,由于存在药物抵抗,常影响其预防效果。本文探讨氯吡格雷和阿司匹林药物遗传学基因检测在缺血性卒中二级预防中的临床价值。方法:纳入2021年7月至2022年9月本院神经内科收治的轻型缺血性脑卒中或短暂性脑缺血发作(TIA)患者220名,随机分成个体化治疗组和氯吡格雷常规治疗组(对照组)。随访一年观察脑卒中复发及出血性事件。结果:(1)与对照组相比,1年随访期个体化治疗组缺血性脑卒中的复发率略低(5.82%vs.7.92%,P>0.05),脑出血风险相似,但其他出血风险增高(6.79%vs.0.99%,P<0.05)。(2)COX回归分析显示卒中风险预测量表(ESRS)评分(HR 2.576,95%CI 1.226-5.413,P=0.013)和高血压病史(HR 5.517,95%CI 1.624-18.737,P=0.006)是缺血性脑卒中复发的独立的风险因素,而与抗栓治疗方案无关(HR 0.918,95%CI 0.291-2.894,P=0.883)。结论:阿司匹林GPIBA、PTGS1、ITGB3基因多态性对指导抗血小板用药临床价值有限,对氯吡格雷CYP2C19*2*3等位基因携带者选择阿司匹林维持治疗,不能显著降低轻型缺血性卒中复发的风险,且可能增加其他出血风险。COX回归分析显示ESRS及高血压病史是卒中复发的独立风险因子。AIM:Clopidogrel and aspirin are commonly used drugs for the secondary prevention of cerebrovascular disease.Due to drug resistance,their preventive effect is often affected.This article explores the clinical value of clopidogrel and aspirin pharmacogenetic genetic testing in the secondary prevention of ischemic stroke.METHODS:220 patients with mild ischemic stroke or TIA admitted to our hospital from 2021.7 to 2022.9 were included and randomly divided into individualized treatment group and clopidogrel conventional treatment group(control group).The patients were followed up for one year to observe stroke recurrence and hemorrhagic events.RESULTS:(1)Compared with the control group,the recurrence rate of ischemic stroke in the individualized treatment group after 1-year follow-up was slightly lower(5.82%vs.7.92%,P>0.05),the risk of cerebral hemorrhage was similar,but the risk of other occurrences was increased(6.79%vs.0.99%,P<0.05).(2)COX regression analysis showed that ESRS(HR 2.576,95%CI 1.226-5.413,P=0.013)and history of hypertension(HR 5.517,95%CI 1.624-18.737,P=0.006)were associated with recurrence of ischemic stroke,independent of antithrombotic regimen(HR 0.918,95%CI 0.291-2.894,P=0.883).CONCLUSION:Aspirin GPIBA,PTGS1,and ITGB3 gene polymorphisms have limited significance in guiding antiplatelet medication.Selecting aspirin maintenance therapy for clopidogrel CYP2C19*2*3 allele carriers cannot significantly reduce the risk of recurrence of minor ischemic stroke and may increase other bleeding risks.COX regression analysis shows that ESRS and history of hypertension are independent risk factors for stroke recurrence.

关 键 词：阿司匹林 氯吡格雷 基因多态性 缺血性脑卒中 二级预防 

分 类 号：R743.33[医药卫生—神经病学与精神病学]