Department of Medicine, McMaster University and Henderson Research Centre, Hamilton, ON, Canada.
N Engl J Med. 2009 Dec 10;361(24):2342-52. doi: 10.1056/NEJMoa0906598.
The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism.
In a randomized, double-blind, noninferiority trial involving patients with acute venous thromboembolism who were initially given parenteral anticoagulation therapy for a median of 9 days (interquartile range, 8 to 11), we compared oral dabigatran, administered at a dose of 150 mg twice daily, with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0. The primary outcome was the 6-month incidence of recurrent symptomatic, objectively confirmed venous thromboembolism and related deaths. Safety end points included bleeding events, acute coronary syndromes, other adverse events, and results of liver-function tests.
A total of 30 of the 1274 patients randomly assigned to receive dabigatran (2.4%), as compared with 27 of the 1265 patients randomly assigned to warfarin (2.1%), had recurrent venous thromboembolism; the difference in risk was 0.4 percentage points (95% confidence interval [CI], -0.8 to 1.5; P<0.001 for the prespecified noninferiority margin). The hazard ratio with dabigatran was 1.10 (95% CI, 0.65 to 1.84). Major bleeding episodes occurred in 20 patients assigned to dabigatran (1.6%) and in 24 patients assigned to warfarin (1.9%) (hazard ratio with dabigatran, 0.82; 95% CI, 0.45 to 1.48), and episodes of any bleeding were observed in 205 patients assigned to dabigatran (16.1%) and 277 patients assigned to warfarin (21.9%; hazard ratio with dabigatran, 0.71; 95% CI, 0.59 to 0.85). The numbers of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in the two groups. Adverse events leading to discontinuation of the study drug occurred in 9.0% of patients assigned to dabigatran and in 6.8% of patients assigned to warfarin (P=0.05).
For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring. (ClinicalTrials.gov number, NCT00291330.)
直接口服凝血酶抑制剂达比加群酯具有可预测的抗凝作用，对于初始接受静脉给予抗凝治疗中位数为 9 天（四分位间距，8 至 11）的急性静脉血栓栓塞症患者，它可能是华法林的替代疗法。
在一项纳入了初始接受静脉给予抗凝治疗中位数为 9 天（四分位间距，8 至 11）的急性静脉血栓栓塞症患者的随机、双盲、非劣效性试验中，我们比较了口服达比加群酯，每日 2 次、每次 150mg 与华法林（调整剂量使国际标准化比值达到 2.0 至 3.0）。主要终点为 6 个月时复发的有症状的、经客观证实的静脉血栓栓塞症和相关死亡。安全性终点包括出血事件、急性冠状动脉综合征、其他不良事件和肝功能检查结果。
在随机分配至接受达比加群酯的 1274 例患者中，有 30 例（2.4%）发生了复发的静脉血栓栓塞症，而随机分配至华法林的 1265 例患者中有 27 例（2.1%）发生了这种情况；风险差异为 0.4 个百分点（95%置信区间[CI]，-0.8 至 1.5；达比加群酯的非劣效性边界预设值为<0.001）。达比加群酯的风险比为 1.10（95%CI，0.65 至 1.84）。接受达比加群酯治疗的 20 例患者（1.6%）和接受华法林治疗的 24 例患者（1.9%）发生了主要出血事件（达比加群酯的风险比，0.82；95%CI，0.45 至 1.48），接受达比加群酯治疗的 205 例患者（16.1%）和接受华法林治疗的 277 例患者（21.9%）发生了任何出血事件（达比加群酯的风险比，0.71；95%CI，0.59 至 0.85）。两组的死亡、急性冠状动脉综合征和肝功能检查异常的例数相似。接受达比加群酯治疗的 9.0%的患者和接受华法林治疗的 6.8%的患者发生了导致停止研究药物治疗的不良事件（P=0.05）。
对于急性静脉血栓栓塞症的治疗，固定剂量的达比加群酯与华法林同样有效，安全性与华法林相似，且不需要实验室监测。（临床试验注册编号，NCT00291330。）
