Eriksson B I, Borris L, Dahl O E, Haas S, Huisman M V, Kakkar A K, Misselwitz F, Kälebo P
Sahlgrenska University HospitalOstra, Gothenburg, Sweden.
J Thromb Haemost. 2006 Jan;4(1):121-8. doi: 10.1111/j.1538-7836.2005.01657.x.
Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants.
To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor--BAY 59-7939--relative to enoxaparin in patients undergoing elective total hip replacement.
In this double-blind, double-dummy, dose-ranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5-9 days after surgery.
Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all-cause mortality; rates were 15%, 14%, 12%, 18%, and 7% for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any significant trend in dose-response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no significant differences between individual BAY 59-7939 doses and enoxaparin.
When efficacy and safety were considered together, the oral, direct FXa inhibitor BAY 59-7939, at 2.5-10 mg b.i.d., compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement.
关节置换手术是研究新型抗凝剂剂量范围的合适模型。
评估一种新型口服直接Xa因子（FXa）抑制剂——BAY 59 - 7939——相对于依诺肝素在接受择期全髋关节置换术患者中的疗效和安全性。
在这项双盲、双模拟、剂量范围研究中，患者被随机分为口服BAY 59 - 7939（2.5、5、10、20或30毫克，每日两次），于术后6 - 8小时开始，或皮下注射依诺肝素40毫克，每日一次，于手术前一晚开始。治疗持续至术后5 - 9天进行强制性双侧静脉造影。
在706例接受治疗的患者中，548例符合主要疗效分析标准。主要疗效终点是任何深静脉血栓形成、非致命性肺栓塞和全因死亡率的发生率；BAY 59 - 7939 2.5、5、10、20和30毫克每日两次组的发生率分别为15%、14%、12%、18%和7%，而依诺肝素组为17%。主要疗效分析未显示BAY 59 - 7939剂量 - 反应关系有任何显著趋势。主要安全终点是术后大出血；随着BAY 59 - 7939剂量增加，事件发生率显著增加（P = 0.045），但BAY 59 - 7939各剂量组与依诺肝素之间无显著差异。
综合考虑疗效和安全性时，口服直接FXa抑制剂BAY 59 - 7939，2.5 - 10毫克每日两次，在预防择期全髋关节置换术患者静脉血栓栓塞方面优于依诺肝素。
