CYP2C19基因快检功能缺失等位基因型sICAS患者氯吡格雷剂量的探索研究  

An exploratory study on clopidogrel dosage in sICAS patients with CYP2C19 loss-of-function alleles under rapid detection

作　　者：时官支 陈国芳 姚美雪[4] 朱晓茹 周晓亚 张文丽 徐辉 刘薇薇[3] 王磊[3] 王琛[3] SHI Guanzhi;CHEN Guofang;YAO Meixue;ZHU Xiaoru;ZHOU Xiaoya;ZHANG Wenli;XU Hui;LIU Weiwei;WANG Lei;WANG Chen(Xuzhou Clinical College,Xuzhou Medical University,Xuzhou,Jiangsu 221009,China;Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou,Jiangsu 221004;Department of Neurology,Xuzhou Central Hospital,Xuzhou,Jiangsu 221009;Department of Epidemiology and Health Statistics,School of Public Health,Xuzhou Medical University,Xuzhou,Jiangsu 221004;Graduate School,Bengbu Medical College,Bengbu,Anhui 233030)

机构地区：[1]徐州医科大学徐州临床学院,江苏徐州221009 [2]江苏省新药研究与临床药学重点实验室,江苏徐州221004 [3]徐州市中心医院神经内科,江苏徐州221009 [4]徐州医科大学公共卫生学院流行病与卫生统计学教研室,江苏徐州221004 [5]蚌埠医学院研究生院,安徽蚌埠233030

出　　处：《徐州医科大学学报》2023年第10期732-738,共7页Journal of Xuzhou Medical University

基　　金：江苏省新药研究与临床药学重点实验室开放研究课题(XZSYSKF2020022);江苏省干部保健科研课题(BJ20007);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：目的探讨不同剂量氯吡格雷联合阿司匹林双联抗血小板治疗对携带CYP2C19功能缺失等位基因型的症状性颅内动脉粥样硬化性狭窄(sICAS)患者的疗效与安全性。方法对2022年2月—9月徐州市中心医院就诊的sICAS患者进行即时颊黏膜取样后CYP2C19基因分型检测,筛选CYP2C192和/或CYP2C193的携带者(CYP2C19功能缺失等位基因),其中携带1个功能缺失等位基因为CYP2C19中间代谢型,携带2个功能缺失等位基因为CYP2C19慢代谢型。将这些携带功能缺失等位基因患者随机分为标准治疗组(氯吡格雷75 mg/d)与强化治疗组(氯吡格雷150 mg/d),2组均联合阿司匹林100 mg,每日1次,双联抗血小板治疗90 d。疗效评估收集2组一般基线资料。采用美国国立卫生研究院卒中量表(NIHSS)及改良Rankin量表(mRS)评分评估2组患者抗血小板治疗前后的神经功能缺损程度及预后情况。结果氯吡格雷强化治疗组治疗7 d、21 d后NIHSS评分与标准治疗组差异无统计学意义(P>0.05)。氯吡格雷强化治疗组治疗90 d NIHSS评分较标准组下降(P<0.01)。多因素Logistic回归分析提示入院NIHSS评分、低密度脂蛋白胆固醇(LDL-C)是临床预后不良的独立危险因素;氯吡格雷强化剂量联合阿司匹林相较于氯吡格雷标准剂量联合阿司匹林治疗sICAS患者90 d不会增加其出血风险(P>0.05),但不能有效降低90 d的卒中复发率(P>0.05)。结论强化剂量氯吡格雷联合阿司匹林较常规剂量氯吡格雷联合阿司匹林治疗携带CYP2C19功能缺失等位基因的sICAS患者,可以更好地改善患者发病90 d后的神经功能缺损症状,且不增加出血转化等不良事件的发生率,但不能有效降低90 d的卒中复发率。Objective To investigate the effectiveness and safety of dual antiplatelet therapy with different doses of clopidogrel combined with aspirin in symptomatic intracranial atherosclerotic stenosis(sICAS)patients with CYP2C19 loss-of-function alleles.Methods The subjects were selected from sICAS patients who were admitted to Xuzhou Central Hospital from February 2022 to September 2022 for immediate buccal mucosal sampling and CYP2C19 genotype testing.The CYP2C192 and/or CYP2C193(CYP2C19 loss-of-function alleles)carriers were screened,where patients carrying one loss-of-function allele were CYP2C19 medium metabolic type,and those with two loss-of-function alleles were CYP2C19 slow metabolic type.These patients carrying loss-of-function alleles were randomly divided into two groups:a standard treatment group(75 mg/d clopidogrel)and an enhanced treatment group(150 mg/d clopidogrel).All the patients were treated with aspirin at 100 mg once a day and received dual antiplatelet therapy for 90 days.Then,their general baseline data were collected for effectiveness evaluation.The degree of neurological deficits and prognosis before and after antiplatelet therapy was evaluated by the National Institute of Health Stroke Scale(NIHSS)and modified Rankin Scale(mRS).Results There was no statistical difference in NIHSS scores between the standard treatment group and the enhanced treatment group after treatment for 7 and 21 days(P>0.05).The enhanced treatment group showed lower NIHSS scores than the standard treatment group after treatment for 90 days(P<0.01).Multivariate logistic regression analysis suggested that NIHSS score at admission and low-density lipoprotein cholesterol(LDL-C)were the independent risk factors for poor clinical prognosis.Compared with the standard dose of clopidogrel combined with aspirin,the combination of the enhanced-dose clopidogrel and aspirin did not increase the bleeding risk of sICAS patients after treatment for 90 days(P>0.05),but did not effectively reduce the recurrence rate of stroke after 90 days

关 键 词：CYP2C19 氯吡格雷 不同剂量 症状性颅内动脉粥样硬化性狭窄 抗血小板 

分 类 号：R735.3[医药卫生—肿瘤]