Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis

Circulation. 2014 Feb 18;129(7):764-72. doi: 10.1161/CIRCULATIONAHA.113.004450. Epub 2013 Dec 16.

Abstract

Background: Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings.

Methods and results: In a randomized, double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or unfractionated heparin for 5 to 11 days, we compared dabigatran 150 mg twice daily with warfarin. The primary outcome, recurrent symptomatic, objectively confirmed VTE and related deaths during 6 months of treatment occurred in 30 of the 1279 dabigatran patients (2.3%) compared with 28 of the 1289 warfarin patients (2.2%; hazard ratio, 1.08; 95% confidence interval [CI], 0.64-1.80; absolute risk difference, 0.2%; 95% CI, -1.0 to 1.3; P<0.001 for the prespecified noninferiority margin for both criteria). The safety end point, major bleeding, occurred in 15 patients receiving dabigatran (1.2%) and in 22 receiving warfarin (1.7%; hazard ratio, 0.69; 95% CI, 0.36-1.32). Any bleeding occurred in 200 dabigatran (15.6%) and 285 warfarin (22.1%; hazard ratio, 0.67; 95% CI, 0.56-0.81) patients. Deaths, adverse events, and acute coronary syndromes were similar in both groups. Pooled analysis of this study RE-COVER II and the RE-COVER trial gave hazard ratios for recurrent VTE of 1.09 (95% CI, 0.76-1.57), for major bleeding of 0.73 (95% CI, 0.48-1.11), and for any bleeding of 0.70 (95% CI, 0.61-0.79).

Conclusion: Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE.

Clinical trial registration url: www.clinicaltrials.gov. Unique identifiers: NCT00680186 and NCT00291330.

Keywords: antagonists & inhibitors; hemorrhage; recurrence; thrombin; venous thromboembolism; warfarin.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Antithrombins / administration & dosage*
  • Antithrombins / adverse effects
  • Benzimidazoles / administration & dosage*
  • Benzimidazoles / adverse effects
  • Dabigatran
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Heparin / administration & dosage
  • Heparin / adverse effects
  • Heparin, Low-Molecular-Weight / administration & dosage
  • Heparin, Low-Molecular-Weight / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Recurrence
  • Risk Factors
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / epidemiology
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects
  • Young Adult
  • beta-Alanine / administration & dosage
  • beta-Alanine / adverse effects
  • beta-Alanine / analogs & derivatives*

Substances

  • Anticoagulants
  • Antithrombins
  • Benzimidazoles
  • Heparin, Low-Molecular-Weight
  • beta-Alanine
  • Warfarin
  • Heparin
  • Dabigatran

Associated data

  • ClinicalTrials.gov/NCT00291330
  • ClinicalTrials.gov/NCT00680186