Are the Dangers of Giving Dabigatran to AF Patients Overblown?

Administering anticoagulation therapy to patients with atrial fibrillation (AF) should be based on clinical facts and not unfounded fears of intracranial bleeding (ICB), suggested new research.

The study assessed the in-hospital mortality rates of AF patients with ICB who received dabigatran or warfarin. Of the 2,391 patients hospitalized with ICB, 531 died. According to the study’s findings, mortality rates were similar among the 2,290 patients on warfarin and the 101 patients on dabigatran at the time of hospitalization. Mortality rates were similar across all ICB subtypes, including the 25 and 723 intracerebral hemorrhages diagnosed in patients on dabigatran and warfarin, respectively.

The researchers said the similar mortality rates could be explained by possible delays in administering warfarin’s reversal agents, dabigatran’s short half-life reducing its impact on bleeding risk, and previous research that has shown lower intracerebral hemorrhage rates and cessation of active bleeding in mice treated with dabigatran.

Dabigatran, one of the new oral anticoagulants (NOACs), effectively reduces risk of ischemic stroke and cardiovascular disease complications in AF patients, but its widespread use is limited by the lack of a reversal agent that can be used if severe bleeding occurs — a major drawback that jeopardizes outcomes and puts patients’ lives at risk, said the researchers.

Idarucizumab, a reversal agent, is currently under development. In late June the U.S. Food and Drug Administration granted it Breakthrough Therapy designation. Its manufacturer is currently conducting phase III trials.

Notably, mortality rates were similar among older and younger patients, those with or without kidney disease, and those at high or low risk of bleeding, regardless of which drug they were on. However, only 11% of 54 men on dabigatran died while hospitalized compared with nearly 30% of 47 women. The opposite trend was true among the 1,272 men and 1,018 women on warfarin: 24% and 20% died, respectively. The researchers had no definite explanation for the difference in mortality between the sexes, but said varying rates of dabigatran metabolism in men and women could have played a role and called for further research to explore that possibility.

The study’s findings contradicted the common belief that patients on dabigatran who experience severe bleeding will suffer worse outcomes than patients on warfarin, and provided additional information for weighing the risks and benefits when deciding which drug to administer to AF patients.

“Reluctance to use dabigatran because of a lack of approved reversal agents is not supported by our results,” said study lead author Dr. Alvaro Alonso, an associate professor in the School of Public Health at the University of Minnesota in Minneapolis. “Whether a patient is prescribed dabigatran or warfarin should be based on other criteria such as patient preference and cost.”

The study was published online inthejournal Stroke.

—Dan Cook

Reference:

1. Alonso A, Bengtson LG, MacLehose RF, Lutsey PL, Chen LY, Lakshminarayan K. Intracranial hemorrhage mortality in atrial fibrillation patients treated with dabigatran or warfarin. Stroke. 2014;45(8):2286-2291.