基于网状Meta分析的CYP2C19功能缺失者的氯吡格雷个体化治疗

CYP2C19 Genotype-guided Individualized Clopidogrel Therapies in Acute Coronary Syndrome/percutaneous Coronary Intervention:A Network Meta-analysis

目的评价不同抗血小板方案治疗携带CYP2C19功能缺失基因ACS/PCI患者的疗效及出血风险。方法两名研究者独立检索中、英文数据库以及国际临床试验注册中心,时间截至2019年6月。以Cochrane偏倚风险量表以及NOS量表评估纳入研究质量;以主要不良心血管事件、血小板抑制率和TIMI出血事件为结局指标。基于频率学理论,应用STATA13.1 Mvmeta包进行定量分析和可视化作图,计算比值比和95%可信区间,预测不同抗血小板方案的效果排序。结果共纳入31个临床研究中22个为随机对照试验,9个为队列研究,涉及5种抗血小板方案。在减少复合心血管事件的发生上,替格瑞洛>西洛他唑>普拉格雷>氯吡格雷150mg>氯吡格雷75mg;在抑制血小板功能上,普拉格雷>替格瑞洛>西洛他唑>氯吡格雷150mg>氯吡格雷75mg;在出血事件的发生率上,替格瑞洛>西洛他唑>氯吡格雷150mg>普拉格雷>氯吡格雷75mg。结论对携带CYP2C19功能缺失基因的ACS或PCI术后患者,优先推荐替阿司匹林和替格瑞洛双联抗血小板;现有证据尚不能证明双倍剂量氯吡格雷、联用西洛他唑、换用普拉格雷此三种方案的有效性。

OBJECTIVE To evaluate the effect and bleeding risk of different antiplatelet regimens for acute coronary syndrome/percutaneous coronary intervention with CYP2 C19 loss-of-function.METHODS Chinese and English databases Patients were searched by two reviewers independently,Cochrane bias tool and NOS were used to evaluate the methodology of included trials;major adverse cardiovascular event,inhibition rate of platelet,TIMI bleeding event were defined as outcomes.Based on the theory of frequency,the STATA13.1 Mvmeta package was applied for quantitative analysis and visualization,and the odds ratio and the 95% confidence interval were calculated,and the order of effect of different antiplatelet regimens was predicted.RESULTS A total of 22 randomized controlled trials were included within 31 clinical studies which involving 5 antiplatelet regimens,and of which,9 were cohort studies.In reducing the incidence of MACCE:ticagrelor>cilostazol>prasugrel>clopidogrel 150 mg>clopidogrel 75 mg.In inhibiting the function of platelet:prasugrel>ticagrelor>cilostazol>clopidogrel 150 mg>clopidogrel 75 mg.The rate of hemorrhagic events:ticagrelor>cilostazol>prasugrel>clopidogrel 150 mg>clopidogrel 75 mg.CONCLUSION For ACS/PCI carriers with CYP2 C19 loss-of –function,aspirin plus ticagrelor might be preferred regimen.The existing evidence can not prove the validity of the double dose clopidogrel,adjunctive cilostazol to dual antiplatelet therapy and alternative prasugrel therpapy.