Lassen M R, Davidson B L, Gallus A, Pineo G, Ansell J, Deitchman D
Department of Orthopaedics and Clinical Trial Unit, Nordsjaellands Hospital Hoersholm, University of Copenhagen, Usseroed Kongevej 102, Hoersholm, Denmark.
J Thromb Haemost. 2007 Dec;5(12):2368-75. doi: 10.1111/j.1538-7836.2007.02764.x. Epub 2007 Sep 15.
Heparins and warfarin are currently used as venous thromboembolism (VTE) prophylaxis in surgery. Inhibition of factor (F) Xa provides a specific mechanism of anticoagulation and the potential for an improved benefit-risk profile.
To evaluate the safety and efficacy of apixaban, a potent, direct, oral inhibitor of FXa, in patients following total knee replacement (TKR), and to investigate dose-response relationships.
PATIENTS/METHODS: A total of 1238 patients were randomized to one of six double-blind apixaban doses [5, 10 or 20 mg day(-1) administered as a single (q.d.) or a twice-daily divided dose (b.i.d.)], enoxaparin (30 mg b.i.d.) or open-label warfarin (titrated to an International Normalized Ratio of 1.8-3.0). Treatment lasted 10-14 days, commencing 12-24 h after surgery with apixaban or enoxaparin, and on the evening of surgery with warfarin. The primary efficacy outcome was a composite of VTE (mandatory venography) and all-cause mortality during treatment. The primary safety outcome was major bleeding.
A total of 1217 patients were eligible for safety and 856 patients for efficacy analysis. All apixaban groups had lower primary efficacy event rates than either comparator. The primary outcome rate decreased with increasing apixaban dose (P = 0.09 with q.d./b.i.d. regimens combined, P = 0.19 for q.d. and P = 0.13 for b.i.d. dosing).A significant dose-related increase in the incidence of total adjudicated bleeding events was noted in the q.d. (P = 0.01) and b.i.d. (P = 0.02) apixaban groups; there was no difference between q.d. and b.i.d. regimens.
Apixaban in doses of 2.5 mg b.i.d. or 5 mg q.d. has a promising benefit-risk profile compared with the current standards of care following TKR.
肝素和华法林目前用于外科手术中静脉血栓栓塞症（VTE）的预防。抑制因子（F）Xa提供了一种特定的抗凝机制，并且有可能改善效益风险比。
评估阿哌沙班（一种强效、直接的口服FXa抑制剂）在全膝关节置换术（TKR）患者中的安全性和有效性，并研究剂量反应关系。
患者/方法：总共1238例患者被随机分配至六种双盲阿哌沙班剂量之一[5、10或20mg每日一次（q.d.）或每日两次分剂量（b.i.d.）给药]、依诺肝素（30mg b.i.d.）或开放标签的华法林（滴定至国际标准化比值为1.8 - 3.0）。治疗持续10 - 14天，阿哌沙班或依诺肝素在术后12 - 24小时开始使用，华法林在手术当晚开始使用。主要疗效结局是治疗期间VTE（强制性静脉造影）和全因死亡率的复合指标。主要安全性结局是大出血。
总共1217例患者符合安全性分析标准，856例患者符合有效性分析标准。所有阿哌沙班组的主要疗效事件发生率均低于任一对照。主要结局发生率随阿哌沙班剂量增加而降低（q.d./b.i.d.方案合并时P = 0.09，q.d.时P = 0.19，b.i.d.给药时P = 0.13）。在阿哌沙班q.d.（P = 0.01）和b.i.d.（P = 0.02）组中，判定的总出血事件发生率有显著的剂量相关增加；q.d.和b.i.d.方案之间无差异。
与TKR术后当前的护理标准相比，每日两次2.5mg或每日一次5mg剂量的阿哌沙班具有良好的效益风险比。
