October 30, 2019
3 min read

Direct oral anticoagulants confer fewer osteoporotic fractures in elderly vs. warfarin

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Elderly patients with atrial fibrillation who were prescribed direct oral anticoagulants had significantly lower risk for osteoporotic fractures than patients who were prescribed vitamin K antagonists such as warfarin, researchers reported.

Both therapies achieved a low absolute incidence for osteoporotic fractures, according to findings published in the Journal of the American College of Cardiology.

Researchers observed that the use of direct oral anticoagulants for the treatment of AF in elderly patients was associated with significantly lower risk for any fracture (HR = 0.85; 95% CI, 0.74-0.97), major osteoporotic fractures (HR = 0.85; 95% CI, 0.72-0.99) and initiating osteoporotic medication (HR = 0.82; 95% CI, 0.71-0.95).

Moreover, researchers found that elderly patients treated with direct oral anticoagulants had a significantly lower risk for the combined endpoint of any fracture or initiation of osteoporosis medication (HR = 0.84; 95% CI, 0.76-0.93).

“This study shows that skeletal health profile should be taken into account when assessing direct oral anticoagulant treatment among patients with atrial fibrillation. Direct oral anticoagulant treatment should not categorically be the choice of drug in all cases, but clinicians need to assess every patient according to comorbidities when choosing oral anticoagulant treatment, and in doing so our findings should be taken into account,” Casper Binding, BMedSc, research fellow in the department of cardiology at Copenhagen University Hospital Herlev and Gentofte in Hellerup, Denmark, told Healio. “It’s obvious that effectiveness and safety should guide the choice of anticoagulation, and oral anticoagulant treatment should be based on the risk of stroke and the risk of major bleeding, but there’s no doubt that patients would benefit greatly from a lower risk of fractures, which is why our findings might be beneficial to take into account.”

In other findings, the standardized absolute 2-year risk for any fracture was low among patients treated with direct oral anticoagulants (absolute risk = 3.1%; 95% CI, 2.9-3.3) and those treated with vitamin K antagonists (absolute risk = 3.8%; 95% CI, 3.4-4.2).

Skeletal health profile

“The take-home message from the study is to take skeletal health profile into account when assessing oral anticoagulant treatment for AF patients,” Binding told Healio. “This study is not setting new guidelines in terms of oral anticoagulant treatment, but it creates awareness of the subject, and since fractures among elderly patients are associated with increased mortality and reduced life quality, it’s important to highlight these findings and to make clinicians aware of the potential connection.”


Using the Danish national registries, researchers analyzed 37,350 elderly patients with AF who were receiving vitamin K antagonists (mean age, 73 years; 56% men; 43% on statins; 75% on beta-blockers) or direct oral anticoagulants (mean age, 72 years; 62% men; 74% on statins; 75% on beta-blockers) for at least 180 days, with the aim of determining the risk for osteoporotic fractures by anticoagulation type.

“Our study did not evaluate risk difference among the different direct oral anticoagulants. Examination of the direct oral anticoagulants separately would be enlightening, as it is unknown if some direct oral anticoagulants contributed more to the results than others,” Binding told Healio. “However, I don’t think that you would see any risk difference among the different direct oral anticoagulants. The hypothesis of the study and the reason why vitamin K antagonists are associated with a higher risk of osteoporotic fractures is based on the biochemical function of vitamin K antagonists and the dietary restrictions accompanying the treatment. On this basis, the different direct oral anticoagulants should all be associated with a lower risk of osteoporotic fractures compared to vitamin K antagonists, but it would be interesting to evaluate the direct oral anticoagulants separately to test the hypothesis.”

Additional evidence

“Binding et al had a strong biochemical basis to search for a link between vitamin K antagonists and osteoporotic fracture,” Brian F. Gage, MD, MSc, professor of medicine at Washington University in St. Louis, wrote in a related editorial. “Their well-done observational study provides additional evidence of this link, but residual confounding may have exaggerated the association. Thus, at least for patients who have AF and no prior osteoporotic fracture (the population studied), the decision to prescribe a vitamin K antagonist or a direct oral anticoagulant should depend on the risks of ischemic stroke, hemorrhage, need for monitoring and affordability rather than on the risk of osteoporotic fracture.” – by Scott Buzby

For more information:

Casper Binding, BMedSc, can be reached at casper@binding.dk.

Disclosures: Binding and Gage report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.