基于CYP2C19基因多态性选择抗血小板药物对急性冠状动脉综合征或经皮冠状动脉介入治疗患者主要心血管事件和出血风险影响的Meta分析

Effect of CYP2C19 Genotype-guided Antiplatelet Therapy on Major Cardiovascular Events and Bleeding Risk in Acute Coronary Syndrome or Undergoing Percutaneous Coronary Intervention Patients:A Meta-analysis

目的:系统评价基于CYP2C19基因多态性选择抗血小板药物对急性冠状动脉综合征(ACS)或经皮冠状动脉介入治疗(PCI)患者主要心血管事件(MACE)和出血事件发生率的影响。方法:计算机检索PubMed、EMbase、The Cochrane Library、CNKI、WanFang Data和Clinicaltrials.gov数据库,搜集评估ACS或PCI患者基于CYP2C19基因指导用药和传统方法选择抗血小板药物治疗的研究,检索时限均为从建库至2022年2月21日。由两位评价员独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用RevMan 5.3软件进行Meta分析。结果:共纳入11篇文献,包括8120例患者。Meta分析结果显示,与基于传统方法选择抗血小板药物治疗组比较,基因指导用药组能够明显降低MACE发生率[RR=0.66,95%CI(0.52,0.85),P=0.001],尤其是显著降低死亡事件发生率[RR=0.73,95%CI(0.55,0.98),P=0.04]、心肌梗死发生率[RR=0.56,95%CI(0.42,0.75),P=0.0001]、支架内血栓事件发生率[RR=0.49,95%CI(0.29,0.83),P=0.008],但是两者靶向血管重建事件发生率[RR=0.88,95%CI(0.64,1.21),P=0.43]以及卒中发生率[RR=0.60,95%CI(0.35,1.04),P=0.07]差异无统计学意义。此外与按照传统方法选择抗血小板药物治疗组相比,基于CYP2C19基因多态性选择抗血小板药物组还能明显降低出血事件发生率[RR=0.83,95%CI(0.70,0.99),P=0.04]。结论:基于CYP2C19基因多态性选择抗血小板药物能够显著降低ACS或PCI患者MACE发生率和出血风险。但上述结论仍需更高质量的多中心随机对照试验予以验证。

Objective:To systematically review the effect of CYP2C19 genotype-guided antiplatelet therapy on major adverse cardiovascular events(MACE)and bleeding risk in acute coronary syndrome(ACS)or undergoing percutaneous coronary intervention(PCI)patients.Methods:PubMed,EMbase,The Cochrane Library CNKI,WanFang Data and ClinicalTrials.gov databases were electronically searched to collect controlled studies comparing CYP2C19 genotype-guided antiplatelet therapy and conventional antiplatelet therapy in ACS or PCI patients from inception to February 21 st,2022.Two reviewers independently screened the literature,extracted the data,and assessed the risk of bias of the included studies.Meta-analysis was performed using RevMan 5.3 software.Results:A total of 11 studies involving 8120 patients were included.The results of meta-analysis showed that compared with the conventional antiplatelet therapy group,the CYP2C19 genotype-guided antiplatelet therapy significantly reduce the risk of MACE(RR=0.66,95%CI 0.52 to 0.85,P=0.001),including significantly decrease the risk of death(RR=0.73,95%CI 0.55 to 0.98,P=0.04),myocardial infarction(RR=0.56,95%CI 0.42 to 0.75,P=0.0001),and stent thrombosis(RR=0.49,95%CI 0.29 to 0.83,P=0.008),but not for targeted vessel revascularization(RR=0.88,95%CI 0.64 to 1.21,P=0.43)and stroke(RR=0.60,95%CI 0.35 to 1.04,P=0.07).In addition,the bleeding events were also significantly decreased(RR=0.83,95%CI 0.70 to 0.99,P=0.04).Conclusion:The CYP2C19 genotype-guided treatment can reduce the rates of MACE and bleeding events compared with the conventional antiplatelet therapy in ACS or PCI patients.However,high quality trials are still required to verify the above conclusion.