冠心病患者个体化抗血小板治疗有效性和安全性的系统评价

Efficacy and Safety of Individualized Antiplatelet Therapy in Patients with Coronary Artery Disease:A Meta-analysis

目的:系统评价冠心病患者根据实验室检测结果进行个体化抗血小板治疗的有效性和安全性,为临床个体化抗血小板治疗提供参考。方法:计算机检索PubMed、Embase和Cochrane图书馆,检索时限为各数据库建库起至2018年2月,收集冠心病患者基于实验室检测结果进行个体化抗血小板治疗对比常规抗血小板治疗的随机对照试验(RCT),提取资料并按照Cochrane系统评价员手册5.2.0进行质量评价后,采用Rev Man 5.3统计软件对主要心血管不良事件、全因死亡、心血管死亡、心肌梗死、支架血栓、卒中、严重出血等指标的发生率进行Meta分析,并对不同种族、实验室检测方法和干预疗程进行亚组分析。结果:共纳入7项RCT,合计8 615例患者。Meta分析结果显示,与常规抗血小板治疗方案相比,基于实验室检测结果的个体化抗血小板治疗患者的主要心血管不良事件[RR=0.93,95%CI(0.74,1.16),P=0.51]、全因死亡[RR=0.89,95%CI(0.56,1.41),P=0.61]、心血管死亡[RR=0.68,95%CI(0.36,1.25),P=0.21]、心肌梗死[RR=1.03,95%CI(0.92,1.16),P=0.56]、支架血栓[RR=0.52,95%CI(0.22,1.24),P=0.14]、卒中[RR=1.03,95%CI(0.65,1.63),P=0.90]和严重出血[RR=0.78,95%CI(0.53,1.14),P=0.20]发生率均无显著性差异。亚组分析结果显示根据CYP2C19基因型进行个体化给药可显著降低主要心血管不良事件发生率[RR=0.29,95%CI(0.14,0.64),P=0.002]和全因死亡发生率[RR=0.11,95%CI(0.01,0.87),P=0.04],而干预疗程达6个月可显著降低全因死亡发生率[RR=0.11,95%CI(0.01,0.87),P=0.04],其余亚组分析中两组患者的各项指标比较,差异均无统计学意义。结论:与常规抗血小板治疗方案相比,对于冠心病患者基于实验室检测结果进行个体化抗血小板治疗并不能显著降低主要心血管不良事件和出血的发生风险。虽然亚组分析显示根据CYP2C19基因型进行个体化给药可显著减少主要心血管不良事件和心血管死亡的发生风险,但该结论尚需更多大样本、高质量研究证实。

OBJECTIVE:To evaluate efficacy and safety of individualized antiplatelet therapy in patients with coronary artery disease(CAD)systematically according to the results of laboratory examination,and to provide reference for individualized antiplatelet therapy in clinic.METHODS:Retrieved from PubMed,Embase and the Cochrane library during the establishment of database to Feb.2018,RCTs about individualized antiplatelet therapy vs.routine antiplatelet therapy in CAD patients based on the results of laboratory examination were collected.Meta-analysis was conducted for the incidence of main adverse cardiovascular adverse events(MACE),all-cause death,cardiovascular death,myocardial infarction,stent thrombosis,stroke and severe bleeding by using Rev Man 5.3 statistical software after data extraction and quality evaluation with Cochrane system evaluator manual 5.2.0.Subgroup analysis was carried out for different races,laboratory testing methods and intervention courses.RESULTS:Totally 7 RCTs involving 8 615 patients were included.Results of Meta-analysis showed that compared with routine antiplatelet therapy,there was no significant difference in the incidence of MACE[RR=0.93,95%CI(0.74,1.16),P=0.51],all-cause death[RR=0.89,95%CI(0.56,1.41),P=0.61],cardiovascular death[RR=0.68,95%CI(0.36,1.25),P=0.21],myocardial infarction[RR=1.03,95%CI(0.92,1.16),P=0.56],stent thrombosis[RR=0.52,95%CI(0.22,1.24),P=0.14],stroke[RR=1.03,95%CI(0.65,1.63),P=0.90],and severe bleeding[RR=0.78,95%CI(0.53,1.14),P=0.20]based on the results of laboratory examination.Subgroup analysis showed according to CYP2C19 genotype,individualized medication could reduce the incidence of MACE[RR=0.29,95%CI(0.14,0.64),P=0.002]and all-cause death[RR=0.11,95%CI(0.01,0.87),P=0.04],and trials with intervention duration of 6 months could significantly decrease the incidence of all-cause death[RR=0.11,95%CI(0.01,0.87),P=0.04],there were no significant difference between 2 groups in other subgroup analysis.CONCLUSIONS:Compared with routine antiplatelet therapy,individualized antiplatelet therapy based on the results of laboratory examination cannot reduce the incidence of MACE and bleeding event risk in real-world patients with CAD.Although subgroup analysis show that individualized medication on the basis of CYP2C19 genotype can significantly reduce the incidence of MACE and cardiovascular death.But more large-scale samples and high-quality studies are needed to confirm this conclusion.