Extended use of dabigatran, warfarin, or placebo in venous thromboembolism

N Engl J Med. 2013 Feb 21;368(8):709-18. doi: 10.1056/NEJMoa1113697.

Abstract

Background: Dabigatran, which is administered in a fixed dose and does not require laboratory monitoring, may be suitable for extended treatment of venous thromboembolism.

Methods: In two double-blind, randomized trials, we compared dabigatran at a dose of 150 mg twice daily with warfarin (active-control study) or with placebo (placebo-control study) in patients with venous thromboembolism who had completed at least 3 initial months of therapy.

Results: In the active-control study, recurrent venous thromboembolism occurred in 26 of 1430 patients in the dabigatran group (1.8%) and 18 of 1426 patients in the warfarin group (1.3%) (hazard ratio with dabigatran, 1.44; 95% confidence interval [CI], 0.78 to 2.64; P=0.01 for noninferiority). Major bleeding occurred in 13 patients in the dabigatran group (0.9%) and 25 patients in the warfarin group (1.8%) (hazard ratio, 0.52; 95% CI, 0.27 to 1.02). Major or clinically relevant bleeding was less frequent with dabigatran (hazard ratio, 0.54; 95% CI, 0.41 to 0.71). Acute coronary syndromes occurred in 13 patients in the dabigatran group (0.9%) and 3 patients in the warfarin group (0.2%) (P=0.02). In the placebo-control study, recurrent venous thromboembolism occurred in 3 of 681 patients in the dabigatran group (0.4%) and 37 of 662 patients in the placebo group (5.6%) (hazard ratio, 0.08; 95% CI, 0.02 to 0.25; P<0.001). Major bleeding occurred in 2 patients in the dabigatran group (0.3%) and 0 patients in the placebo group. Major or clinically relevant bleeding occurred in 36 patients in the dabigatran group (5.3%) and 12 patients in the placebo group (1.8%) (hazard ratio, 2.92; 95% CI, 1.52 to 5.60). Acute coronary syndromes occurred in 1 patient each in the dabigatran and placebo groups.

Conclusions: Dabigatran was effective in the extended treatment of venous thromboembolism and carried a lower risk of major or clinically relevant bleeding than warfarin but a higher risk than placebo. (Funded by Boehringer Ingelheim; RE-MEDY and RE-SONATE ClinicalTrials.gov numbers, NCT00329238 and NCT00558259, respectively.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Benzimidazoles / adverse effects
  • Benzimidazoles / therapeutic use*
  • Dabigatran
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Humans
  • Intention to Treat Analysis
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Recurrence
  • Risk
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / mortality
  • Warfarin / adverse effects
  • Warfarin / therapeutic use*
  • Young Adult
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*
  • beta-Alanine / therapeutic use

Substances

  • Benzimidazoles
  • beta-Alanine
  • Warfarin
  • Dabigatran

Associated data

  • ClinicalTrials.gov/NCT00329238
  • ClinicalTrials.gov/NCT00558259