Extended Use of Dabigatran, Warfarin, or Placebo in Venous Thromboembolism

作者：Schulman, Sam^*; Kearon, Clive; Kakkar, Ajay K.; Schellong, Sebastian; Eriksson, Henry; Baanstra, David; Kvamme, Anne Mathilde; Friedman, Jeffrey; Mismetti, Patrick; Goldhaber, Samuel Z.

来源：New England Journal of Medicine, 2013, 368(8): 709-718.

DOI：10.1056/NEJMoa1113697

• ORAL ANTICOAGULANT-THERAPY
• MOLECULAR-WEIGHT HEPARIN
• LONG-TERM
• UNFRACTIONATED HEPARIN
• ATRIAL-FIBRILLATION
• PULMONARY-EMBOLISM
• INITIAL TREATMENT
• RANDOMIZED-TRIAL
• 1ST EPISODE
• PREVENTION

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.)

• 出版日期2013-2-21