title: Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis.
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.
  
  
  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).
  
  
  CONCLUSIONS
  Dabigatran has similar effects on VTE recurrence and a lower risk of bleeding compared with warfarin for the treatment of acute VTE.
  
  
  BACKGROUND
  www.clinicaltrials.gov. Unique identifiers: NCT00680186 and NCT00291330.
authors.affiliation: Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada (S. Schulman, C.K.); Department of Hematology, Karolinska University Hospital, Stockholm, Sweden (S.S.); Thrombosis Research Institute and University College London, London, UK (A.K.K.); Brigham and Women's Hospital, Harvard Medical School, Boston, MA (S.Z.G.); Medical Division 2, Municipal Hospital Friedrichstadt, Dresden, Germany (S. Schellong); Department of Medicine, Sahlgrenska University Hospital-Östra, Gothenburg, Sweden (H.E.); Department of Vascular Pathology, Bellevue Hospital, Saint Etienne, France (P.M.); Clinical Research, Boehringer Ingelheim, Copenhagen, Denmark (A.V.C.); Boehringer Ingelheim, Ridgefield, CT (J.F.); Boehringer Ingelheim, Reims, France (F.L.M.); and Boehringer Ingelheim, Biberach and der Riss, BDM, Germany (N.P.).
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Kakkar
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schellong
authors.forename: Henry
authors.initials: H
authors.lastname: Eriksson
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.forename: Anita Vedel
authors.initials: AV
authors.lastname: Christiansen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Friedman
authors.forename: Florence
authors.initials: F
authors.lastname: Le Maulf
authors.forename: Nuala
authors.initials: N
authors.lastname: Peter
authors.forename: Clive
authors.initials: C
authors.lastname: Kearon
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D000069604:Dabigatran; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006493:Heparin / Q000008:administration & dosage / Q000009:adverse effects; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000453:epidemiology; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult; D015091:beta-Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D001562:Benzimidazoles; D006495:Heparin, Low-Molecular-Weight; D015091:beta-Alanine; D014859:Warfarin; D006493:Heparin; D000069604:Dabigatran
keywords: antagonists & inhibitors; hemorrhage; recurrence; thrombin; venous thromboembolism; warfarin