The RE-COVER trial: Dabigatran non-inferior to warfarin in treating acute venous thromboembolism [Classics Series]

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1. The RE-COVER trial demonstrates that treating acute venous thromboembolism with 6 months of dabigatran 150 mg twice daily is non-inferior to dose-adjusted warfarin to an INR of 2-3.

2. Though dabigatran therapy does not require INR monitoring, it is considerably more expensive than warfarin.

Study Rundown: The RE-COVER trial demonstrated that in patients with acute venous thromboembolism, dabigatran is non-inferior to warfarin in preventing symptomatic venous thromboembolism or death associated with venous thromboembolism. One common criticism of the study is that Boehringer Ingelheim played a large part in designing and conducting the trial. It is also important to note that treatment with dabigatran is considerably more expensive than warfarin, and that dabigatran should only be considered in patients with sufficient renal function.

In sum, dabigatran is non-inferior to warfarin in treating acute venous thromboembolism. Although dabigatran treatment does not require regular INR checks, it is much more costly than warfarin.

Please click to read study in NEJM

In Depth [randomized, controlled study]: The RE-COVER trial, published in NEJM in 2009, was a randomized, double-blind, non-inferiority trial comparing dabigatran with warfarin in the treatment of acute venous thromboembolism. A total of 2,564 patients were randomized to receive either 6 months of dabigatran 150 mg twice daily or dose-adjusted warfarin with a target INR of 2-3. Patients in both groups were initially treated with at least 5 days of parenteral anticoagulation prior to starting on their oral anticoagulants. Notably, the study was funded, designed, and conducted by Boehringer Ingelheim (the manufacturer of dabigatran) in conjunction with the study steering committee. The primary efficacy endpoint was a composite of symptomatic venous thromboembolism or death associated with venous thromboembolism in the 6 month period after randomization. Patients were assessed at 7 days after randomization, and then monthly for 6 months.

Patients were recruited from 228 different centres in 29 countries. Parenteral anticoagulation was given for a mean of 10 days in both groups. With regards to the primary efficacy outcome, dabigatran was found to be non-inferior to warfarin. There were no significant differences between the two groups in terms of the incidence of major bleeding, though patients in the warfarin group experienced a significantly higher rate of any bleeding event. There were significantly more patients in the dabigatran group who experienced an adverse event that led to discontinuation of the study drug (HR 1.33; 95% CI 1.01-1.76), and patients in the dabigatran group also experienced significantly higher incidence of dyspepsia compared to the warfarin group (2.9% in dabigatran group, 0.6% in warfarin group).

By Adrienne Cheung, Andrew Cheung, M.D.

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