Dabigatran Etexilate Versus Warfarin in the Treatment of Venous Thromboembolism.

Abstract 1

Background. The direct oral thrombin inhibitor, dabigatran etexilate, has a predictable anticoagulant effect and may be an alternative to warfarin in patients with acute venous thromboembolism (VTE). Methods. In a randomized, double-blind, trial of 2539 patients with acute VTE, treated with low molecular weight or unfractionated heparin for 5 to 11 days, we compared oral dabigatran etexilate, 150 mg twice daily in a fixed-dose, with warfarin dose-adjusted to an International Normalized Ratio of 2.0 and 3.0, each given for 6 months. The primary outcome was symptomatic, objectively confirmed recurrent VTE or VTE-related death up to 6 months of treatment. Safety endpoints included bleeding events, acute coronary syndrome, liver function tests, vital signs and adverse events. Results. Of 1274 patients randomized to dabigatran etexilate, at 6 months 30 (2.4%) had recurrent VTE compared with 27 (2.2%) of 1265 patients randomized to warfarin; risk difference 0.4% [95 percent confidence interval, −0.8 to 1.5]; p<0.0001 for prespecified non-inferiority margin. During the planned study participation, through the end of the follow-up period, there were 34 vs. 32 patients who had recurrent VTE in the dabigatran etexilate vs. warfarin treated groups, respectively (hazard ratio 1.05 [95% confidence interval, 0.065 to 1.70]). Major bleeding occurred in 20 patients treated with dabigatran etexilate and 24 patients treated with warfarin (hazard ratio 0.82; 95 percent confidence interval, 0.45 to 1.48) and any bleeding occurred in 207 versus 280 patients, respectively (hazard ratio 0.71, 95 percent confidence interval, 0.59 to 0.85). Death, acute coronary syndromes, and liver function test abnormalities were infrequent and similar in the two groups. Conclusion: Fixed-dose dabigatran etexilate is as effective and safe as warfarin in the treatment of acute VTE.