即时检测CYP2C19基因型精准指导下高危非致残性缺血性脑血管事件的抗血小板治疗  

Efficacy analysis of anti-platelet in the treatment of high-risk non-disabling ischemic cerebrovascular events guided by point-of-care testing of CYP2C19 gene

作　　者：朱晓茹 陈国芳 姚美雪 时官支 周晓亚 张文丽 王磊 刘薇薇 徐辉 王琛 Zhu Xiaoru;Chen Guofang;Yao Meixue;Shi Guanzhi;Zhou Xiaoya;Zhang Wenli;Wang Lei;Liu Weiwei;Xu Hui;Wang Chen(Xuzhou Clinical College of Xuzhou Medical University,Department of Neurology,Xuzhou Central Hospital,Xuzhou 221009,China;Department of Epidemiology and Health Statistics,School of Public Health,Xuzhou Medical University,Xuzhou 221004,China;Xuzhou Clinical College of Xuzhou Medical University,Xuzhou 221009,China;Graduate School of Bengbu Medical College,Bengbu 233030,China)

机构地区：[1]徐州医科大学徐州临床学院、徐州市中心医院神经内科,徐州221009 [2]徐州医科大学公共卫生学院流行病与卫生统计学教研室,徐州221004 [3]徐州医科大学徐州临床学院,徐州221009 [4]蚌埠医学院研究生院,蚌埠233030

出　　处：《中华神经科杂志》2023年第4期365-373,共9页Chinese Journal of Neurology

基　　金：江苏省研究生科研与实践创新计划(SJCX22_1284);江苏省干部保健科研课题(BJ20007);江苏省新药研究与临床药学重点实验室开放研究课题(XZSYSKF2020022);徐州市医学领军人才培养项目(XWRCHT20210037);徐州市推动科技创新专项资金项目(KC21213)。

摘　　要：目的探讨在即时检测CYP2C19基因型的精准指导下,不同双重抗血小板方案治疗高危非致残性缺血性脑血管事件(HR-NICE)的有效性及安全性。方法采用单中心、前瞻性、随机、开放标签、终点盲法设计。连续收集2020年7月至2022年1月于徐州市中心医院脑卒中绿色通道及神经内科病房收治的HR-NICE患者,对所有患者无创刮取颊黏膜行即时检测,筛选CYP2C19功能缺失等位基因CYP2C19*2和CYP2C19*3的携带者,携带1个功能缺失等位基因为CYP2C19中代谢,携带2个功能缺失等位基因为CYP2C19慢代谢,使用全自动医用PCR分析仪进行即时检测CYP2C19基因型,将检测周转时间缩短至1 h。将CYP2C19基因型为中慢代谢的患者按照随机数字表法分为常规治疗组(氯吡格雷75 mg,1次/d)、替格瑞洛组(替格瑞洛90 mg,2次/d)和强化剂量组(氯吡格雷150 mg,1次/d),分别联合阿司匹林100 mg,1次/d双重抗血小板治疗21 d。收集3组患者的一般基线资料、急性卒中Org10172治疗试验分型及90 d改良Rankin量表(mRS)评分、不良事件及严重不良事件发生等情况。主要疗效结局为90 d内新发卒中,主要安全结局为90 d内严重或中度出血。结果共纳入716例HR-NICE患者,常规治疗组240例、替格瑞洛组240例、强化剂量组236例,3组患者基线资料差异均无统计学意义(均P>0.05)。90 d新发卒中患者常规治疗组26例(10.8%),替格瑞洛组11例(4.6%),强化剂量组4例(1.7%),3组间差异具有统计学意义(χ^(2)=19.28,P<0.05)。其中常规治疗组与替格瑞洛组(χ^(2)=6.59,P=0.010)、常规治疗组与强化剂量组(χ^(2)=16.83,P<0.001)差异均具有统计学意义,而替格瑞洛组与强化剂量组差异无统计学意义(P>0.05)。90 d中重度出血患者常规治疗组1例(0.4%),替格瑞洛组6例(2.5%),强化剂量组0例,3组间差异具有统计学意义(χ^(2)=7.23,P<0.05),其中替格瑞洛组与强化剂量组差异具有统计学意义(P=0.030)。CYP2C19基因检�Objective To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events(HR-NICE)guided by point-of-care testing of CYP2C19 gene.Methods A single-centre,prospective,randomised,open-label,and blinded endpoint design was uesd in the study.From July 2020 to January 2022,HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital,and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing.Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles.This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype.CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group(clopidogrel 75 mg,once a day),the ticagrelor group(ticagrelor 90 mg,twice a day)and the intensive dose group(clopidogrel 150 mg,once a day)separately combined with aspirin(100 mg,once a day)dual antiplatelet for 21 days.Baseline information,Acute Stroke Org 10172 Treatment Trial staging,90-day modified Rankin Scale score,occurrence of adverse events and severe adverse events were collected for all the 3 groups.The primary efficacy outcome was new stroke within 90 days,and the primary safety outcome was severe or moderate bleeding within 90 days.Results A total of 716 patients were included:240 in the conventional treatment group,240 in the ticagrelor group and 236 in the intensive dose group.There was no statistically significant difference between the 3 groups at baseline(all P>0.05).There were 26 cases(10.8%)with new stroke events in the conventional treatment group,11 cases(4.6%)in the ticagrelor group and 4 cases(1.7%)in the intensive dose group

关 键 词：细胞色素P-450 CYP2C19 即时检测 氯吡格雷 替格瑞洛 脑缺血发作 短暂性 

分 类 号：R743[医药卫生—神经病学与精神病学]