脑梗死患者他汀类药物与氯吡格雷动态抵抗的相关性  

Correlation Between Statins and Clopidogrel Dynamic Resistance in Patients with Cerebral Infarction

作　　者：石红婷[1] 尧慧燕 董亚贤[1] 钟高贤[1] 刁芳明[1] 李秋玲[1] 徐鋆阳[1] 陈霄莲[1] SHI Hongting;YAO Huiyan;DONG Yaxian;ZHONG Gaoxian;DIAO Fangming;LI Quilin;XU Junyang;CHEN Xiaoliang(Department of Neurology,the Second Affiliated Hospital,Guangzhou Medical University,Guangzhou 511447,China)

机构地区：[1]广州医科大学附属第二医院神经内科

出　　处：《医药导报》2020年第2期181-186,共6页Herald of Medicine

基　　金：广东省医学科学技术研究基金项目(B2018028)

摘　　要：目的探讨在脑梗死患者中不同细胞色素P450(CYP)3A4代谢的他汀类药物对氯吡格雷动态抵抗发生的影响。方法选择150例脑梗死患者,筛选出非氯吡格雷抵抗(NCR)患者,然后随机分为阿托伐他汀组(阿托伐他汀20 mg·d-1+氯吡格雷75 mg·d-1,AC组)和瑞舒伐他汀组(瑞舒伐他汀10 mg·d-1+氯吡格雷75 mg·d-1,RC组)。NCR进一步分为动态氯吡格雷抵抗组(DCR组)与持续无氯吡格雷抵抗组(CNCR组)。采用比浊法测定所有患者服药前、服用氯吡格雷后2周的血小板聚集率(PAR),且NCR患者测定氯吡格雷加他汀治疗后1个月及3个月的PAR。结果AC组发生DCR为19例(33.9%),RC组6例(11.3%),两组差异有统计学意义(P<0.05);服用他汀类药物前,AC组与RC组PAR比较差异无统计学意义(P>0.05),但服用他汀类药物后两组不同时间段PAR比较差异有统计学意义(F=13.913,P<0.01);总胆固醇[OR=3.27,95%CI(1.56,6.84),P=0.002]、三酰甘油[OR=2.35,95%CI(1.21,4.57),P=0.012]、既往糖尿病史[OR=5.06,95%CI(1.13,22.67),P=0.034]为发生DCR的独立危险因素,且DCR组与CNCR组不同时间段PAR比较差异有统计学意义(F=116.680,P<0.01)。结论经CYP3A4代谢他汀类药物(阿托伐他汀)影响氯吡格雷的抗血小板功能,增加DCR的发生率,同时DCR的发生与总胆固醇、三酰甘油及既往糖尿病史有关。Objective To investigate the effect of different CYP3A4-metabolized statins on the development of clopidogrel dynamic resistance in patients with cerebral infarction.Methods A total of 150 patients with cerebral infarction,non-clopidogrel resistance(NCR)patients were identified and randomly divided into atorvastatin group(atorvastatin 20 mg·d-1+clopidogrel 75 mg·d-1,AC group)and rosuvastatin group(rosuvastatin10 mg·d-1+clopidogrel 75 mg·d-1,RC group).The NCR patients were further divided into dynamic clopidogrel resistance(DCR)and continuous NCR(CNCR)subgroups.Platelet aggregation rate(PAR)of all patients before and 2 weeks after clopidogrel administration was measured by turbidimetric method.PAR of NCR patients after 1 and 3 months of posttreatment with clopidogrel plus statins was also evaluated.Results Compared with the DCR ratio(19 cases,33.9%)of the AC group,the DCR ratio(6 cases,11.3%)of the RC group was significantly different(P<0.05).Before taking statin,there was no significant difference in PAR between AC and RC groups(P>0.05).However,after taking statin,significant difference in PAR was observed between the AC and RC groups at different time points(F=13.913,P<0.01).Total cholesterol[OR=3.27,95%CI(1.56,6.84),P=0.002],triglycerides[OR=2.35,95%CI(1.21,4.57),P=0.012]and diabetes history[OR=5.06,95%CI(1.13,22.67),P=0.034]were independent risk factors for DCR.There were significant differences in PAR between DCR groups and CNCR groups in different time periods(F=116.680,P<0.01).Conclusion Statins,which were metabolized via CYP3A4,could affect the antiplatelet function of clopidogrel and increase the incidence of DCR.Meanwhile,the occurrence of DCR may be correlated with total cholesterol,triglycerides and previous diabetes history.

关 键 词：他汀类药物 氯吡格雷动态抵抗 脑梗死 CYP3A4代谢 二级预防 

分 类 号：R972[医药卫生—药品] R973.2[医药卫生—药学]