Dabigatran was noninferior to warfarin for preventing recurrent venous thromboembolism (HR 1.44; 95% CI 0.78-2.64; P=0.01 for noninferiority) and superior to placebo (HR 0.08; P<0.001).
RCT (n=4,199)
Double-blind
randomized
Does dabigatran 150 mg twice daily prevent recurrent venous thromboembolism in patients with VTE who have completed at least 3 initial months of therapy compared to warfarin or placebo?
Dabigatran is an effective alternative to warfarin for extended VTE treatment, offering a lower risk of major bleeding but a slightly higher risk of acute coronary syndromes.
Effect estimate: HR 1.44 (95% CI 0.78 to 2.64)
Absolute Event Rate: 1.8% vs 1.3%
p-value: p=0.01 for noninferiority
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.).
Schulman et al. (2013) conducted an RCT in Venous thromboembolism (n=4,199). Dabigatran vs. Warfarin or placebo was evaluated on Recurrent venous thromboembolism (active-control study) (HR 1.44, 95% CI 0.78 to 2.64, p=0.01 for noninferiority). Dabigatran was noninferior to warfarin for preventing recurrent venous thromboembolism (HR 1.44; 95% CI 0.78-2.64; P=0.01 for noninferiority) and superior to placebo (HR 0.08; P<0.001).