Dabigatran versus warfarin in the treatment of acute venous thromboembolism.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.)

• Authors: Sam Schulman, Clive Kearon, Ajay K Kakkar, Patrick Mismetti, Sebastian Schellong, Henry Eriksson, David Baanstra, Janet Schnee, Samuel Z Goldhaber, RE-COVER Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 361 Issue 24 Pg. 2342-52 (Dec 10 2009) ISSN: 1533-4406 [Electronic] United States
• PMID: 19966341 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Massachusetts Medical Society.

Chemical References

• Anticoagulants
• Benzimidazoles
• Pyridines
• Warfarin
• Dabigatran

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anticoagulants (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Dabigatran
• Double-Blind Method
• Female
• Humans
• International Normalized Ratio
• Male
• Middle Aged
• Pyridines (adverse effects, therapeutic use)
• Recurrence
• Risk
• Venous Thromboembolism (drug therapy)
• Warfarin (adverse effects, therapeutic use)
• Young Adult