Dabigatran has been compared with warfarin for treatment of acute venous thromboembolism in one previous trial (RE-COVER). Based on the low rate of the primary outcome as the RE-COVER study was running, we undertook this replica study to confirm the results of RE-COVER, and to allow for more rigorous sub-group analyses.
In a randomized, double-blind, double-dummy trial of 2568 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, dose-adjusted to an International Normalized Ratio of 2.0 and 3.0, each given for 6 months. Primary outcome was recurrent symptomatic, objectively confirmed venous thromboembolism and deaths related to venous thromboembolism during 6 months. Safety endpoints included bleeding events, acute coronary syndrome, elevated liver function tests, and adverse events.
Of 1279 patients randomized to dabigatran, 30 (2.4%) had recurrent VTE compared with 28 (2.2%) of 1289 patients randomized to warfarin; risk difference 0.2% (95% confidence interval [CI], −1.0 to 1.5); p<0.0001 for the pre-specified non-inferiority margin. The hazard ratio for dabigatran was 1.08 (95% CI, 0.64 to 1.80). Major bleeding occurred in 15 patients treated with dabigatran and 22 patients treated with warfarin (hazard ratio 0.69; 95% CI, 0.36 to 1.32) and any bleeding occurred in 200 versus 285 patients, respectively (hazard ratio 0.67, 95% CI, 0.56 to 0.81). The frequency of reported ACS events was less than 1% in the trial, with more cases in the dabigatran treatment group than those treated with warfarin. There were 25 deaths during each treatment, and serious adverse events were similar in the two groups. Analysis of outcomes based on demographic characteristics showed consistency of effects for both safety and efficacy. This included the analysis based on Asian race, which had been limited in RE-COVER. There were 537 Asian patients in RE-COVER II compared to only 65 in RE-COVER. The event rates of recurrent VTE and of any bleeding were similar in Asians and non-Asians.
The study confirms that the efficacy of dabigatran is non-inferior to warfarin in the treatment of acute VTE and with a lower risk for bleeding. The safety of dabigatran is similar in the Asian population compared with non-Asians.
Off Label Use: dabigatran for treatment of venous thromboembolism. Christiansen:Boehringer Ingelheim: Employment. Schnee:Boehringer Ingelheim: Employment.