Dabigatran noninferior to warfarin for preventing VTE recurrence

In patients who had a previous venous thromboembolism (VTE), dabigatran prevented recurrence about as well as warfarin and caused fewer bleeding events, according to two new manufacturer-sponsored trials of extended treatment.

The results of both trials were published together in the Feb. 21 New England Journal of Medicine.

In the first double-blind trial, almost 3,000 patients with VTE, who were thought to be at high risk of recurrence, completed three months of initial therapy and then were randomized to warfarin or twice-daily dabigatran at a dose of 150 mg. The length of study treatment ranged from six to 36 months.

Recurrent VTE occurred in 1.8% of dabigatran patients compared to 1.3% of warfarin patients, a finding that met the study's prespecified threshold for noninferiority. The dabigatran patients had fewer major bleeds and fewer major or clinically relevant bleeds, but only the latter combined outcome showed a statistically significant difference.

In the second double-blind trial, about 1,300 similar patients were randomized to the same dabigatran treatment or to placebo. The dabigatran group had many fewer VTE recurrences (0.4% vs. 5.6%; hazard ratio, 0.08; P<0.001) than the placebo group, but more major (0.3% vs. 0) and major or clinically relevant (5.3% vs. 1.8%) bleeds.

The study authors concluded that dabigatran was effective in extended treatment of VTE and carried a lower risk of major or clinically relevant bleeding than warfarin, but a higher one than placebo. They noted that the efficacy of dabigatran compared to placebo was similar to that shown by rivaroxaban and warfarin in other studies.

However, the study was not able to resolve concerns about an association between dabigatran and acute coronary syndromes (ACS). In the first trial, ACS occurred in 13 (0.9%) dabigatran patients and 3 (0.2%) warfarin patients, and it occurred in one patient in each of the groups in the placebo trial.

Based on results like these, targeted anticoagulants are an appealing alternative to warfarin, according to an accompanying editorial, which noted that dabigatran has not yet been FDA-approved for extended treatment of VTE. However, the editorialist cautioned, there are still questions and concerns about these new drugs, including the current lack of an antidote and the challenge of selecting appropriate patients for treatment.