Eriksson B I, Dahl O E, Büller H R, Hettiarachchi R, Rosencher N, Bravo M-L, Ahnfelt L, Piovella F, Stangier J, Kälebo P, Reilly P
Sahlgrenska University Hospital/Ostra, Göteborg, Sweden.
J Thromb Haemost. 2005 Jan;3(1):103-11. doi: 10.1111/j.1538-7836.2004.01100.x.
Dabigatran etexilate is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolism (VTE) following orthopedic surgery.
In a multicenter, parallel-group, double-blind study, 1973 patients undergoing total hip or knee replacement were randomized to 6-10 days of oral dabigatran etexilate (50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily), starting 1-4 h after surgery, or subcutaneous enoxaparin (40 mg once daily) starting 12 h prior to surgery. The primary efficacy outcome was the incidence of VTE (detected by bilateral venography or symptomatic events) during treatment.
Of the 1949 treated patients, 1464 (75%) patients were evaluable for the efficacy analysis. VTE occurred in 28.5%, 17.4%, 16.6%, 13.1% and 24% of patients assigned to dabigatran etexilate 50, 150 mg twice daily, 300 mg once daily, 225 mg twice daily and enoxaparin, respectively. A significant dose-dependent decrease in VTE occurred with increasing doses of dabigatran etexilate (P < 0.0001). Compared with enoxaparin, VTE was significantly lower in patients receiving 150 mg twice daily [odds ratio (OR) 0.65, P = 0.04], 300 mg once daily (OR 0.61, P = 0.02) and 225 mg twice daily (OR 0.47, P = 0.0007). Compared with enoxaparin, major bleeding was significantly lower with 50 mg twice daily (0.3% vs. 2.0%, P = 0.047) but elevated with higher doses, nearly reaching statistical significance with the 300 mg once-daily dose (4.7%, P = 0.051).
Oral administration of dabigatran etexilate, commenced early in the postoperative period, was effective and safe across a range of doses. Further optimization of the efficacy/safety balance will be addressed in future studies.
达比加群酯是一种口服直接凝血酶抑制剂，正在接受评估用于预防骨科手术后的静脉血栓栓塞（VTE）。
在一项多中心、平行组、双盲研究中，1973例接受全髋关节或膝关节置换术的患者被随机分配，术后1 - 4小时开始口服达比加群酯6 - 10天（50mg、150mg每日两次、300mg每日一次、225mg每日两次），或术前12小时开始皮下注射依诺肝素（40mg每日一次）。主要疗效指标是治疗期间VTE的发生率（通过双侧静脉造影或有症状事件检测）。
在1949例接受治疗的患者中，1464例（75%）患者可进行疗效分析。分配到达比加群酯50mg、150mg每日两次、300mg每日一次、225mg每日两次和依诺肝素组的患者中，VTE发生率分别为28.5%、17.4%、16.6%、13.1%和24%。随着达比加群酯剂量增加，VTE发生率呈显著剂量依赖性下降（P < 0.0001）。与依诺肝素相比，接受150mg每日两次（比值比[OR] 0.65，P = 0.04）、300mg每日一次（OR 0.61，P = 0.02）和225mg每日两次（OR 0.47，P = 0.0007）的患者VTE发生率显著更低。与依诺肝素相比，50mg每日两次时严重出血显著更低（0.3%对2.0%，P = 0.047），但高剂量时升高，300mg每日一次剂量时几乎达到统计学显著性（4.7%，P = 0.051）。
术后早期开始口服达比加群酯在一系列剂量范围内有效且安全。疗效/安全性平衡的进一步优化将在未来研究中探讨。
