低剂量利伐沙班在冠心病患者抗栓治疗中出血风险的Meta分析

Risk of Bleeding in Patients with Coronary Artery Disease Adding Low Dose Rivaroxaban:a Meta-Analysis

目的系统评价低剂量利伐沙班(5 mg·d^-1)在冠心病患者抗栓治疗中的出血风险。方法检索Medline、Embase、Cochrane Library、中国知网(CNKI)、维普期刊资源整合服务平台(CQVIP)和万方数据知识服务平台,检索时限为各数据库建库起至2020年6月,获得冠心病患者基于常规抗血小板治疗方案中加入低剂量利伐沙班的随机对照试验(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,采用Rev Man 5.3统计软件对出血事件的发生率进行Meta分析,包括主要复合安全性终点事件、大出血、小出血、需要医疗的出血和致命性出血等。结果共纳入5项RCTs合计36 319例患者。Meta分析结果显示,加用低剂量利伐沙班可显著增加主要复合安全性终点事件[RR=1.55,95%CI(1.05,2.28),P=0.03]、大出血[RR=1.88,95%CI(1.58,2.25),P<0.000 01]、小出血[RR=1.70,95%CI(1.52,1.89),P<0.000 01]和需要医疗的出血风险[RR=1.41,95%CI(1.04,1.90),P=0.03],但不增加致命性出血的发生风险[RR=1.00,95%CI(0.58,1.73),P=0.99],同时主要复合有效性终点事件的发生风险[RR=0.88,95%CI(0.77,1.00),P=0.04]显著降低。结论抗血小板治疗仍是冠心病患者预防主要不良心血管事件的金标准,而对于高危缺血风险且出血风险较低的患者也可联合低剂量利伐沙班抗栓治疗,但无论选择何种方案均应个体化且动态地评估患者的获益与风险。

OBJECTIVE To systematically evaluate the risk of bleeding in patients with coronary artery disease(CAD) adding low dose rivaroxaban. METHODS Randomized controlled trials(RCTs) which focused on adding low dose rivaroxaban to conventional antiplatelet therapy in patients with CAD were systematically searched in databases of MEDLINE, EMBASE, Cochrane’s Library, CNKI, CQVIP and Wanfang from the establishment of each database to June 2020. Meta-analysis was conducted for the incidence of bleeding events including the composite primary safety outcome, major bleeding and fatal bleeding by using Rev Man 5.3 statistical software after data extraction and quality evaluation with Cochrane system evaluator manual 5.2.0. RESULTS Five RCTs involving 36 319 patients were included for our Meta-analysis. Patients adding low dose rivaroxaban had a significantly higher risk of the composite primary safety outcome [RR=1.55,95% CI(1.05,2.28),P=0.03], major bleeding [RR=1.88,95% CI(1.58,2.25),P<0.000 01], minor bleeding [RR=1.70,95% CI(1.52,1.89),P<0.000 01] and bleeding requiring medical attention [RR=1.41,95% CI(1.04,1.90),P=0.03], without increasing the risk of fatal bleeding [RR=1.00,95% CI(0.58,1.73),P=0.99]. Meanwhile, the risk of the composite primary efficacy outcome was significantly reduced [RR=0.88,95% CI(0.77,1.00),P=0.04]. CONCLUSION Anti-platelet therapy is still the gold standard for the prevention of major adverse cardiovascular events in patients with CAD. However, adding low dose rivaroxaban could provide an additional therapeutic choice for patients with high risk of ischemia and low risk of bleeding. Clinicians should personally and dynamically evaluate the benefit and risk of individual patient.