Fisher William D, Eriksson Bengt I, Bauer Kenneth A, Borris Lars, Dahl Ola E, Gent Michael, Haas Sylvia, Homering Martin, Huisman Menno V, Kakkar Ajay K, Kälebo Peter, Kwong Louis M, Misselwitz Frank, Turpie Alexander G G
McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada.
Thromb Haemost. 2007 Jun;97(6):931-7.
Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N = 722), and one in patients undergoing total knee replacement (TKR; N = 621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5-9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1-24.4% of per-protocol patients receiving rivaroxaban 5-60 mg, and 27.8% receiving enoxaparin (n = 914). There was a flat dose response relationship between rivaroxaban and total VTE (p = 0.39). Major bleeding (safety population, n = 1,317) increased dose-dependently with rivaroxaban (p < 0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5-20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery.
利伐沙班（BAY 59 - 7939）是一种口服的直接Xa因子抑制剂，正处于临床开发阶段，用于预防和治疗静脉血栓栓塞症（VTE）。这项对利伐沙班用于大型骨科手术后VTE预防的两项II期研究汇总结果的分析，旨在强化各单项研究的结论。一项研究在接受全髋关节置换术（THR；N = 722）的患者中进行，另一项在接受全膝关节置换术（TKR；N = 621）的患者中进行。在两项研究中，患者均被随机、双盲分配，术后开始口服利伐沙班，每日两次（bid），或皮下注射依诺肝素（THR术前开始每日一次40 mg，TKR术后开始每日两次30 mg）。治疗持续至术后5 - 9天进行强制性双侧静脉造影。在接受5 - 60 mg利伐沙班的符合方案患者中，16.1% - 24.4%发生了总VTE（深静脉血栓形成、肺栓塞和全因死亡率），而接受依诺肝素的患者中这一比例为27.8%（n = 914）。利伐沙班与总VTE之间存在平坦的剂量反应关系（p = 0.39）。大出血（安全人群，n = 1317）随利伐沙班剂量增加而呈剂量依赖性增加（p < 0.001），接受利伐沙班每日总剂量5、10、20、40和60 mg的患者中，大出血发生率分别为0.9%、1.3%、2.1%、3.9%和7.0%，而接受依诺肝素的患者中这一比例为1.7%。未进行常规凝血监测，THR和TKR后利伐沙班的剂量反应关系之间无显著差异。总体而言，相对于依诺肝素，利伐沙班每日总剂量5 - 20 mg在预防大型骨科手术后VTE方面具有最有利的疗效和安全性平衡。
