A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement
A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement
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DOI：
10.1161/circulationaha.106.642074
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发表时间：
2006-11-28
期刊：
影响因子：
37.8
通讯作者：
Kalebo, Peter
中科院分区：
文献类型：
--
作者：
Eriksson, Bengt I.;Borris, Lars C.;Kalebo, Peter
利伐沙班（BAY 59-7939）是一种口服、直接的Xa因子抑制剂，可能是肝素和华法林的替代品，用于预防和治疗血栓栓塞性疾病。方法和结果：这项随机、双盲、双虚拟、主动对照、多国、剂量范围研究评估了每日一次的利伐沙班相对于依诺肝素预防选择性全髋关节置换术患者静脉血栓栓塞的有效性和安全性。患者（n = 873）被随机分为每日一次口服利伐沙班剂量5,10,20,30或40mg（手术后6至8小时开始）或每日一次皮下注射依诺肝素剂量40mg（手术前晚上和手术后6小时给予）。研究药物继续使用5 - 9天；第二天进行强制双侧静脉造影。分别在接受5、10、20、30和40mg利伐沙班和40mg依诺肝素治疗的患者中观察到14.9%、10.6%、8.5%、13.5%、6.4%和25.2%的主要终点（n = 618，每个方案人群）。两组疗效无显著剂量-反应关系（P = 0.0852）。接受5、10、20、30、40 mg利伐沙班和40 mg依诺肝素治疗的患者中，分别有2.3%、0.7%、4.3%、4.9%、5.1%和1.9% （n = 845，安全人群）出现术后大出血，呈显著的剂量-反应关系（P = 0.0391）。结论：利伐沙班在全髋关节置换术后预防血栓的疗效和安全性与依诺肝素相似，每日一次口服给药方便，无需凝血监测。当考虑到有效性和安全性时，这些结果表明，应该在III期研究中研究每日一次10mg利伐沙班。
Background - Rivaroxaban (BAY 59-7939) -an oral, direct Factor Xa inhibitor-could be an alternative to heparins and warfarin for the prevention and treatment of thromboembolic disorders.Methods and Results - This randomized, double-blind, double-dummy, active-comparator-controlled, multinational, dose-ranging study assessed the efficacy and safety of once-daily rivaroxaban relative to enoxaparin for prevention of venous thromboembolism in patients undergoing elective total hip replacement. Patients (n = 873) were randomized to once-daily oral rivaroxaban doses of 5, 10, 20, 30, or 40 mg (initiated 6 to 8 hours after surgery) or a once-daily subcutaneous enoxaparin dose of 40 mg (given the evening before and >= 6 hours after surgery). Study drugs were continued for an additional 5 to 9 days; mandatory bilateral venography was performed the following day. The primary end point (composite of any deep vein thrombosis, objectively confirmed pulmonary embolism, and all-cause mortality) was observed in 14.9%, 10.6%, 8.5%, 13.5%, 6.4%, and 25.2% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n = 618, per-protocol population). No significant dose-response relationship was found for efficacy (P = 0.0852). Major postoperative bleeding was observed in 2.3%, 0.7%, 4.3%, 4.9%, 5.1%, and 1.9% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n = 845, safety population), representing a significant dose-response relationship (P = 0.0391).Conclusions - Rivaroxaban showed efficacy and safety similar to enoxaparin for thromboprophylaxis after total hip replacement, with the convenience of once-daily oral dosing and without the need for coagulation monitoring. When both efficacy and safety are considered, these results suggest that 10 mg rivaroxaban once daily should be investigated in phase III studies.