Warfarin more harmful to bone health than DOACs

A study published in JAMA Internal Medicine last month found that direct oral anticoagulants (DOACs) were more effective in minimizing AFib patients’ risk of experiencing fracture than warfarin, supporting the theory that the blood thinner might be harmful to bone health.

Warfarin’s effect on bone health has been questioned for more than a decade now, first author Pamela L. Lutsey, PhD, of the University of Minnesota School of Public Health, and colleagues wrote in JAMA, and a handful of studies have linked the drug to impaired bone quality and increased fracture risk. Warfarin also carries an inherent risk for potentially major bleeds, but the drug continues to circulate among AFib patients as a means to prevent cardioembolic complications. 

When DOACs such as dabigatran, rivaroxaban, apixaban and edoxaban hit the market several years ago, they presented an alternative to warfarin for patients with atrial fibrillation. Studies found DOACs were as effective as warfarin for preventing stroke and CV events while reducing patients’ risk of bleeding, but, Lutsey et al. said, “the existing evidence is inconsistent.”

“Given present uncertainty regarding whether fracture risk differs according to type of OAC therapy and the need to optimize AFib management to avoid unintended consequences and maximize quality of life, we used data from the MarketScan administrative claims databases to test the hypothesis that, among patients with nonvalvular atrial fibrillation, use of DOACs vs. warfarin is associated with lower risk of incident clinical fracture,” the authors wrote.

The team’s comparative effectiveness cohort study included 167,275 patients with nonvalvular AFib who were prescribed OACs between January 2010 and September 2015. Patients were matched for age, sex, CHA2DS2VASc score and high-dimensional propensity scores.

Lutsey and colleagues noted 817 hip fractures, 2,013 hospitalized fractures and 7,294 total fractures in the study population over a mean 17 months of follow-up. Relative to new users of warfarin, new users of DOACs saw a 13% reduced risk of suffering fractures requiring hospitalization and a 7% lower risk of suffering any clinical fracture. The drugs’ association with hip fractures was statistically insignificant.

The study’s strongest DOAC seemed to be apixaban—the drug was linked to a 33% reduced risk of hip fracture, a 40% reduced risk of fracture requiring hospitalization and a 14% reduced risk of any clinical fracture. The authors reported that in subgroup analyses, DOACs seemed most beneficial among AFib patients who had concomitant osteoporosis.

“The strongest effect estimates were observed when comparing apixaban and warfarin; this finding was not hypothesized and, as such, warrants further scrutiny,” Lutsey and co-authors wrote. “Collectively, our findings support the notion that warfarin may be harmful to bone health.”

The researchers said their findings could be particularly relevant in an older population.

“Optimizing care of patients with AFib is paramount,” they wrote. “Given the detrimental effects of fracture in the elderly, caution should be used when prescribing warfarin to patients with AFib at elevated fracture risk.”