缺血性脑卒中患者发生氯吡格雷抵抗的危险因素分析  

Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke

作　　者：王亚娟 赵燕 李维亮 余爱荣 WANG Yajuan;ZHAO Yan;LI Weiliang;YU Airong(Hubei University of Science and Technology,Xianning 437000,China;Department of Clinical Pharmacy,Central Theater General Hospital,Wuhan 430070,China)

机构地区：[1]湖北科技学院,湖北咸宁437000 [2]中部战区总医院临床药学科,湖北武汉430070

出　　处：《药学实践与服务》2024年第1期32-37,共6页Journal of Pharmaceutical Practice and Service

摘　　要：目的 探讨缺血性脑卒中患者服用氯吡格雷治疗后发生药物抵抗的危险因素,为促进临床个体化药物治疗提供依据。方法 选取202例诊断为缺血性脑卒中的住院患者,入中部战区总医院后均给予双抗治疗(阿司匹林+氯吡格雷),住院期间通过芯片杂交法检测CYP2C19基因型,将CYP2C19基因多态性根据药物代谢类型分为快代谢组、中代谢组和慢代谢组。患者服药7~14 d根据血栓弹力图(TEG)检测由腺苷二磷酸(ADP)诱导的血小板抑制率,将ADP<30%为氯吡格雷药物抵抗组,ADP≥30%为非抵抗组。采用Logistic回归分析研究发生氯吡格雷抵抗的危险因素。结果 202例缺血性脑卒中患者中,抵抗组87例,非抵抗组115例。氯吡格雷抵抗组合并糖尿病的患者比例和白细胞计数水平高于非抵抗组,差异均具有统计学意义(P<0.05)。CYP2C19中代谢组患者发生氯吡格雷抵抗的比例显著高于快代谢组,血小板抑制率也明显低于快代谢组,差异均具有统计学意义(P<0.05)。结论 合并糖尿病、高白细胞计数水平及CYP2C19中代谢型是缺血性脑卒中患者发生氯吡格雷抵抗的独立危险因素。Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy.Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment(aspirin+clopidogrel).CYP2C19 genotype was detected by microarray hybridization during hospitalization,and CYP2C19 gene polymorphisms were classified into fast metabolism group,medium metabolism group and slow metabolism group according to the type of drug metabolism.Patients were tested for platelet inhibition induced by adenosine diphosphate(ADP)according to thromboelastographic(TEG)on 7~14 d of drug administration.ADP<30%was classified as clopidogrel drug resistance group and ADP≥30%as non-resistance group.Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance.Results Among 202 patients with ischemic stroke,87 were in the resistant group and 115 in the non-resistant group.The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group,and the differences were statistically significant(P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group,and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group,all with statistically significant differences(P<0.05).Conclusion Combined diabetes mellitus,high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

关 键 词：缺血性脑卒中 氯吡格雷抵抗 血栓弹力图 细胞色素氧化酶P450酶2C19 危险因素 

分 类 号：R743.3[医药卫生—神经病学与精神病学]