冠心病介入術後服用氯吡格雷治療出現不良心血管事件與CYP2C19基因多態性關係的薈萃分析

Meta-Analysis of CYP2C19 Polymorphism and Clinical Outcome Following Stent Implantation with on-Clopidogrel Treatment in Patients with Coronary Artery Disease

目的探討經皮冠狀動脈介入治療(Percutaneous Coronary Intervent ion,PCI)術後應用氯吡格雷治療發生主要不良心血管事件(Major Adverse Cardiovascular Events,MACE)與攜帶CYP2C19*2和(或)*3基因者之間的關像,為PCI術後患者醢床應用氯吡格雷治療提供更進一-步認識。方法在The Cochrane Library、PubMed、EMbase、萬方、知網資料庫檢索相關文獻,由兩位研究員獨立進行文獻篩選和評價,探用RevMan5.2整理資料薈萃分析。結果納入39篇文獻,共33989例研究對象。薈萃分析結果顯示:與非攜帶組比較,攜帶組發生MACE(OR,1.48;9S%CI,1.24~1.76;P<0.0001).支架内血栓(OR,2.18;9S%CI,1.84~2.59;P<0.00001)、非致死性心肌梗死(OR,1.45;954CI,1.27~1.65;P<0.00001).靶病變血運重建/靶血管血運重建(Target Lesion Revascularization,TLR/Target Vessel Revascularization,TVR)(OR,1.78;95%CI,1.09-2.90;P20.02)的風險高;但兩組發生心源性死亡.出血事件的風險無統計學意義。結論CP2C19基因多態性與冠心病PCI術後口服氯吡格雷治療的患者出現MACE存在正相關,提示攜帶CYP2C19功能缺失基因者發生支架内血栓、非致死性心肌梗死、TLR/TVR的風險更高。

Objective e aim of this study was to assess the association between the CYP2C19*2 and*3 polymorphism and the major adverse cardiovascular events(MACE)in patients treated with clopidogrel after percutaneous coronary intervention(PCI).Methods Prospective cohort studies,post-hoc analyses and case-control studies of randomized controlled trials were identi ed from the databases of PubMed,EMbase,the Cochrane Library and Wanfang,CNKI. e endpoints were MACE,stent thrombosis,non-fatal myocardial infarction,cardiovascular death,repeat revascularization,major bleeding events.Combined odds risks(OR)with 95%con dence intervals(CI)were computed for each outcome by using standard methods of meta-analysis and test parameters.Results 33989 patients from 39 trials were analyzed.Compared with non-carriers of the CYP2C19 variant alleles,CYP2C19*2 and*3 polymorphism was associated with higher risk of MACE(OR,1.48;95%CI,1.24-1.76;P<0.0001),stent thrombosis(OR,2.18;95%CI,1.84-2.59;P<0.00001),non-fatal myocardial infarction(OR,1.45;95%CI,1.27-1.65;P<0.00001),repeat revascularization(OR,1.78;95%CI,1.09-2.90;P=0.02).No di erence was seen in cardiovascular death and major bleeding events.Conclusion Carrrier status for CYP2C19*2 and*3 polymorphism is associated with signi cantly increase adverse clinical events in patients with PCI on clopidogrel therapy.