December 18th, 2013

New Trial Confirms Role for Dabigatran in Venous Thromboembolism

A new study helps support a role for  the new oral anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim) in patients with venous thrombosis (VTE).  The RE-COVER II trial, published online in Circulation, confirms the finding of the earlier and highly similar RE-COVER trial, published in the New England Journal of Medicine in 2009, that dabigatran is as safe and effective as warfarin for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Dabigatran is currently approved only for stroke prevention in patients with non-valvular atrial fibrillation.

In RE-COVER II, 2589 patients with acute VTE were  randomized to dabigatran or warfarin following standard heparin treatment for 5 to 11 days. At 6 months, the rate of recurrent VTE and related deaths was 2.3% in the dabigatran group versus 2.2% in the warfarin group (HR 1.08, CI 0.64 – 1.80; p<0.001 for noninferiority). There were no significant differences in the incidence of deaths, adverse events, and acute coronary syndromes.

Major bleeding, the primary safety endpoint, occurred in 1.2% of the dabigatran group and 1.7% of the warfarin group (HR 0.69. CI 0.36 – 1.32). There was a significant reduction in total bleeds: 15.6% versus 22.1% (HR 0.67, CI 0.56 – 0.81).

A pooled analysis of both RE-COVER trials turned up similar hazard ratios: recurrent VTE: 1.09 (CI 0.76 – 1.57), major bleeding: 0.73 (CI 0.48 – 1.11), and total bleeds: 0.70 (CI 0.61 – 0.79).

The findings are broadly consistent with the VTE trials for the other new oral anticoagulants — apixaban, rivaroxaban, and edoxaban — according to the authors. In all the trials, the newer agents were noninferior to warfarin in efficacy and had lower bleeding rates.

In an accompanying editorial, Peter Verhamme and Henri Bounameaux write that RE-COVER II is the last of the phase III trials studying the newer anticoagulants in the acute treatment of VTE. They agree with the study authors that all the drugs have now shown noninferiority to warfarin along with less bleeding.

One clinically important issue is that apixaban and rivaroxaban were studied using a single-drug approach, making these drugs preferable in patients for whom outpatient treatment is possible. The new agents, they write, “offer patients, physicians and healthcare systems an effective, safer, and more convenient treatment for acute VTE.”


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