McMaster University, Hamilton, Ontario, Canada.
Thromb Haemost. 2011 Mar;105(3):444-53. doi: 10.1160/TH10-09-0601. Epub 2010 Dec 6.
Four phase III studies compared oral rivaroxaban with subcutaneous enoxaparin for the prevention of venous thromboembolism (VTE) after total hip or knee arthroplasty (THA or TKA). A pooled analysis of these studies compared the effect of rivaroxaban with enoxaparin on symptomatic VTE plus all-cause mortality and bleeding events, and determined whether these effects were consistent in patient subgroups. Patients (N=12,729) aged ≥18 years and scheduled for elective THA or TKA received rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily or 30 mg every 12 hours. The composite of symptomatic VTE and all-cause mortality, the prespecified primary efficacy endpoint and adjudicated bleeding events were analysed in the day 12± 2 active treatment pool. Subgroup analyses of these outcomes were performed over the total treatment period. In the day 12± 2 pool, the primary efficacy endpoint occurred in 29/6,183 patients receiving rivaroxaban (0.5%) versus 60/6,200 patients receiving enoxaparin (1.0%; p=0.001). Major bleeding occurred in 21 (0.3%) versus 13(0.2%) patients, p=0.23; major plus non-major clinically relevant bleeding in 176(2.8%) versus 152 (2.5%) patients, p=0.19; and any bleeding in 409 (6.6%) versus 384 (6.2%) patients, p=0.38, respectively. The reduction of symptomatic VTE plus all-cause mortality was consistent across prespecified subgroups (age, gender, body weight, creatinine clearance) in the total treatment period. Compared with enoxaparin regimens, rivaroxaban reduces the composite of symptomatic VTE and all-cause mortality after elective THA or TKA, with a small increase in bleeding, no signs of compromised liver safety and fewer serious adverse events.
四项三期研究比较了口服利伐沙班与皮下依诺肝素预防全髋关节或全膝关节置换术后静脉血栓栓塞症（VTE）。对这些研究的汇总分析比较了利伐沙班与依诺肝素对症状性 VTE 加全因死亡率和出血事件的影响，并确定这些影响在患者亚组中是否一致。年龄≥18 岁且计划择期接受全髋关节或全膝关节置换术的患者接受利伐沙班 10 mg 每日一次或依诺肝素 40 mg 每日一次或 30 mg 每 12 小时一次。症状性 VTE 加全因死亡率的复合终点，即主要疗效终点和经裁决的出血事件在第 12 天±2 天的活性治疗池内进行分析。对这些结果进行了整个治疗期间的亚组分析。在第 12 天±2 天的活性治疗池内，利伐沙班组有 29/6183 例（0.5%）患者发生主要疗效终点事件，依诺肝素组有 60/6200 例（1.0%）患者（p=0.001）。大出血事件分别发生在 21 例（0.3%）和 13 例（0.2%）患者中（p=0.23）；主要和非主要临床相关出血事件分别发生在 176 例（2.8%）和 152 例（2.5%）患者中（p=0.19）；任何出血事件分别发生在 409 例（6.6%）和 384 例（6.2%）患者中（p=0.38）。在整个治疗期间，全髋关节或全膝关节置换术后症状性 VTE 加全因死亡率的降低在所有预设亚组（年龄、性别、体重、肌酐清除率）中均一致。与依诺肝素方案相比，利伐沙班可降低择期全髋关节或全膝关节置换术后症状性 VTE 加全因死亡率，出血略有增加，但无肝脏安全性受损迹象，且严重不良事件更少。
