title: Extended use of dabigatran, warfarin, or placebo in venous thromboembolism.
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.).
authors: Department of Medicine, McMaster University and Thrombosis and Atherosclerosis Research Institute, Hamilton, ON, Canada. schulms@mcmaster.ca
authors: Sam
authors: S
authors: Schulman
authors: Clive
authors: C
authors: Kearon
authors: Ajay K
authors: AK
authors: Kakkar
authors: Sebastian
authors: S
authors: Schellong
authors: Henry
authors: H
authors: Eriksson
authors: David
authors: D
authors: Baanstra
authors: Anne Mathilde
authors: AM
authors: Kvamme
authors: Jeffrey
authors: J
authors: Friedman
authors: Patrick
authors: P
authors: Mismetti
authors: Samuel Z
authors: SZ
authors: Goldhaber
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000069604:Dabigatran; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D057194:Intention to Treat Analysis; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012306:Risk; D054556:Venous Thromboembolism / Q000188:drug therapy* / Q000401:mortality; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D001562:Benzimidazoles; D015091:beta-Alanine; D014859:Warfarin; D000069604:Dabigatran