利伐沙班预防关节置换术后静脉血栓形成有效性与安全性的Meta分析

A meta-analysis of rivaroxaban effectiveness and safety for the prevention of thromboembolism after total hip or knee arthroplasty

目的评价利伐沙班与依诺肝素预防髋膝关节置换术后静脉血栓栓塞的有效性与安全性。方法计算机检索Cochrane图书馆、MEDLINE、EMBASE、CNKI、万方数据库和中国生物医学文献数据库,手工检索相关文献的参考文献及主要中文骨科杂志。收集所有比较利伐沙班和依诺肝素预防髋膝关节置换术后静脉血栓栓塞症(venous thromboembolism,VTE)的中、英文随机对照研究,评价纳入研究的方法学质量并提取资料。统计软件采用Cochrane协作网提供的RevMan5.2。结果共纳入10项随机对照试验,共计16 007例患者。与依诺肝素相比,利伐沙班显著降低了髋膝关节置换术后总VTE和全因致死发生率[RR=0.53,95%CI (0.36,0.77),P<0.05]、重大VTE发生率[RR=0.38,95%CI (0.19,0.74),P<0.05]、症状性VTE发生率[RR=0.47,95%CI (0.32,0.68),P<0.05]及深静脉血栓形成(deep vein thrombosis,DVT)发生率[RR=0.52,95%CI (0.36,0.76),P<0.05],在总出血事件[RR=1.12,95%CI (1.00,1.26),P=0.05]、重大出血事件[RR=1.67,95%CI (0.98,2.84),P=0.06]、额外输血事件[RR=0.82,95%CI (0.63,1.08),P=0.16]及药物相关不良反应事件[RR=1.01,95%CI (0.92,1.10),P=0.90]发生率方面二者差异无统计学意义,虽然增加了整体临床相关非重大出血事件发生率[RR=1.27,95%CI (1.03,1.55),P<0.05],但各亚组间差异无统计学意义。结论与依诺肝素相比,利伐沙班更加有效地降低了髋膝关节置换术后静脉血栓的发生率,且没有增加出血风险。

Objective To assess the effectiveness and safety of rivaroxaban versus enoxaparin for thromboprophylaxis after total hip or knee arthroplasty. Methods Randomized controlled trials( RCTs) comparing rivaroxaban and enoxaparin were retrieved in Cochrane library, MEDLINE, EMBASE, CNKI, Wanfang Data and Chinese Biomedical Database by computer, and major Chinese orthopedic journals manually. Meta-analysis was performed by statistical software RevMan 5.2. Results Ten RCTs involving 16 007 cases were included in the Metaanalysis. Compared with enoxaparin, rivaroxaban significantly decreased the incidence of VTE and all-cause mortality [ RR = 0.53, 95% CI( 0.36, 0.77), P < 0.05 ], major VTE [ RR = 0.38, 95% CI( 0.19, 0.74), P < 0.05 ], symptomatic VTE [ RR = 0.47, 95% CI( 0.32, 0.68), P < 0.05 ] and DVT [ RR = 0.52, 95% CI( 0.36, 0.76), P < 0.05 ];but the differences in any bleeding events [ RR = 1.12, 95% CI( 1.00, 1.26), P = 0.05 ], major bleeding events [ RR = 1.67, 95% CI( 0.98, 2.84), P = 0.06 ], additional blood transfusion [ RR = 0.82, 95% CI( 0.63, 1.08), P = 0.16 ] and drugrelated adverse events [ RR = 1.01, 95% CI( 0.92, 1.10), P = 0.90 ] between the two drugs were not statistically significant. The incidence of clinically relevant non-major bleeding events in the rivaroxaban group was significantly higher, but with no statistical differences in the subgroups. Conclusions Rivaroxaban is more effective than the recommended dose of enoxaparin, which has a similar safety profile for thromboprophylaxis after total hip or knee arthroplasty.