Dabigatran to Treat Patients with Acute Venous Thromboembolism

New Orleans—A prespecified subgroup analysis of 2 randomized, phase 3 trials that included patients with acute venous thromboembolism (VTE) found that there was no difference in recurrent VTE or VTE-related mortality if they received dabigatran with or without concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicyclic acid (ASA). In addition, there was no increase in bleeding risks when patients took an NSAID or low-dose ASA in addition to dabigatran.

The results were presented during a poster presentation at the ASH meeting. The poster was titled Influence of Concomitant NSAID or ASA on the Efficacy and Safety of Dabigatran Versus Warfarin for the Treatment of Acute Venous Thromboembolism: A Pooled Analysis from RE-COVER^™ and RE-COVER^™ II.

In the United States, the incidence of VTE is expected to increase from 950,000 people in 2006 to 1.82 million in 2050, according to the study authors. They mentioned the standard treatment is rapidly-acting parenteral anticoagulation for 5 to 7 days and then at least 3 months of treatment with a vitamin K antagonist.

The FDA approved dabigatran in October 2010 to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. The drug, a direct thrombin inhibitor, is administered orally in 75 mg and 150 mg capsules. Boehringer Ingelheim, the drug’s manufacturer, submitted a supplemental approval to the FDA in August 2013 for the use of dabigatran in patients with VTE. Outside of the United States, dabigatran is approved to prevent VTE in patients undergoing total hip or knee replacement surgery.

Two randomized, double-blind trials of patients who were at least 18 years of age and had acute symptomatic VTE found dabigatran was as effective as warfarin and was associated with a lower risk of bleeding. Patients were allowed to receive ≤100 mg of ASA per day or an NSAID with a half-life of ≤12 hours.

This pooled analysis included 2553 patients who received dabigatran and 2554 patients who took warfarin. The mean age was 54.8 years, 59.5% of patients were male, and 86.1% were white.

There was no difference in the groups in the incidence of VTE or VTE-related deaths, which was the study’s primary end point. For instance, of the patients in the dabigatran group, the primary end point occurred in 2.6% of patients not taking an NSAID, 2.8% of patients taking an NSAID, 2.6% of patients not taking ASA, and 3.1% of patients taking ASA. Of the patients in the warfarin group, the primary end point occurred in 2.5% of patients not receiving an NSAID, 2% of patients receiving an NSAID, 2.4% of patients not receiving ASA, and 2.3% of patients receiving ASA.

Major bleeding events, the primary safety end point, were also similar in the groups or less frequent in patients receiving dabigatran. Of the patients in the dabigatran group, major bleeding events occurred in 0.9% of patients not taking an NSAID, 1.1% of patients taking an NSAID, 1% of patients not taking ASA, and 1% of patients taking ASA. Of the patients in the warfarin group, the primary safety end point occurred in 1.8% of patients not receiving an NSAID, 1% of patients receiving an NSAID, 1.5% of patients not receiving ASA, and 3% of patients receiving ASA.

This study was funded by Boehringer Ingelheim.