DOD study: Dabigatran favorable to warfarin for stroke, major bleeding

CHICAGO — In a retrospective analysis conducted by the US Department of Defense, dabigatran was favorable to warfarin for stroke and major bleeding outcomes, according to findings presented at the American Heart Association Scientific Sessions.

Lt. Col. Todd C. Villines, MD, and colleagues conducted a retrospective cohort analysis using the DOD Military Health System database. They evaluated the safety and effectiveness of dabigatran (Pradaxa, Boehringer Ingelheim) compared with warfarin in patients with nonvalvular atrial fibrillation who had a first prescription claim for dabigatran or warfarin from October 2010 to July 2012.

They conducted a propensity-matched analysis of 12,793 participants in each group. The primary outcomes were stroke and major bleeding.

Fewer events in dabigatran group

Compared with warfarin, dabigatran was associated with a 27% reduced risk for stroke (dabigatran group, 0.92 event rate per 100 patient-years; warfarin group, 1.32 event rate per 100 patient-years; HR=0.73; 95% CI, 0.55-0.97) and a trend toward a 13% reduced risk for major bleeding (dabigatran group, 3.08 event rate per 100 patient-years; warfarin group, 3.7 event rate per 100 patient-years; HR=0.87; 95% CI, 0.74-1.02).

“Data like these are important because they demonstrate the favorable risk–benefit profile of Pradaxa in real-world settings,” Villines, from the Walter Reed National Military Medical Center, Bethesda, Md., said in a press release. “These efficacy and safety results are consistent with what we’ve seen in the pivotal RE-LY study, and support its findings in a very large, diverse and older patient population that is typical of the [nonvalvular] AF patients clinicians see every day.”

Among secondary outcomes, dabigatran was associated with lower rates of hemorrhagic stroke (HR=0.32; 95% CI, 0.14-0.73), major intracranial bleeding (HR=0.49; 95% CI, 0.3-0.79), major urogenital bleeding (HR=0.36; 95% CI, 0.18-0.74), major other bleeding (HR=0.38; 95% CI, 0.22-0.66), MI (HR=0.65; 95% CI, 0.45-0.95) and death (HR=0.64; 95% CI, 0.55-0.74) compared with warfarin. However, dabigatran was associated with higher rates of major lower gastrointestinal bleeding compared with warfarin (HR=1.3; 95% CI, 1.04-1.62), the researchers found.

New data for antidote

In another presentation at AHA 2014, researchers reported that idarucizumab, an investigational antidote for dabigatran, restored wound-site formation of fibrin, a key component of blood clotting, in healthy volunteers given dabigatran.

Joanne van Ryn, PhD, from the department of cardiometabolic disease research at Boehringer Ingelheim, and colleagues measured levels of fibrinopeptide A, a marker of fibrin formation at a wound site, in 35 healthy volunteers at baseline, after administration of dabigatran and after administration of idarucizumab.

At baseline, the mean level of fibrinopeptide A was 3,981 ng/mL; 2.5 hours after administration of dabigatran, it was 208 ng/mL, an approximately 95% decrease; and 30 minutes after administration of idarucizumab, fibrinopeptide A levels were restored to 24% of baseline levels for patients given 1 g, 45% of baseline levels for those given 2 g, and 95% of baseline levels for those given 4 g (P<.05).

In patients given 2 g or 4 g of idarucizumab, anticoagulation levels were reversed in circulating blood.

“These data are the first to show idarucizumab restores dabigatran-induced inhibition of wound-site fibrin formation,” van Ryn said in a press release. “The findings from this subanalysis complement earlier findings which showed that idarucizumab provides immediate, complete and sustained reversal of the anticoagulation effects of dabigatran.” – by Erik Swain

For more information:

Van Ryn J. Abstract #18403.

Villines TC. Abstract #18353. Both presented at: American Heart Association Scientific Sessions; Nov. 15-19, 2014; Chicago.

Disclosure: Van Ryn is an employee of Boehringer Ingelheim. Villines reports speaking for Boehringer Ingelheim.