Fracture risk higher with warfarin compared to DOACs: JAMA

USA: In patients with atrial fibrillation (AF), the use of warfarin compared with newer direct oral anticoagulants (DOACs) increases the risk of fractures, finds a recent study published in the journal JAMA Internal Medicine. These findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture and DOACs -- particularly apixaban -- should be preferred for AF patients at increased risk of fractures.

Warfarin, an anticoagulant, is used for the prevention of cardioembolic complications in patients with atrial fibrillation. Whether warfarin use is associated with adverse effects on bone health is controversial. The availability of alternate DOAC options now makes it possible to evaluate the comparative safety of warfarin in association with fracture risk.

Pamela L. Lutsey, University of Minnesota School of Public Health, Minneapolis, and colleagues determined whether the use of DOACs (dabigatran etexilate, rivaroxaban, and apixaban) versus warfarin is associated with a lower risk of incident fracture in patients with nonvalvular AF.

For the purpose, the researchers conducted a comparative effectiveness cohort study of patients with nonvalvular AF prescribed oral anticoagulants from January 1, 2010, through September 30, 2015, using the MarketSan claims database. A total, 167, 275 patients were included in the study—the mean age of the cohort was 68.9 (12.5) years and 62% were men.

DOACs included in the study were dabigatran etexilate, rivaroxaban, and apixaban. Of the treatments compared in the study, 10.6% received apixaban, 18.9% received dabigatran etexilate, 21.% received rivaroxaban, and 49.4% received warfarin.

The main outcome measures of the study were an incident hip fracture, fractures requiring hospitalizations, and all clinical fractures, which investigators identified through the use of inpatient and outpatient claims. In an effort to reduce confounding, investigators matched patients based on sex, age, CHA2DS2-VASc score, and high-dimensional propensity scores.

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Key findings of the study include:

• A total of 817 hip fractures, 2013 hospitalized fractures, and 7294 total fractures occurred during a mean (SD) follow-up of 16.9 (13.7) months.


• In multivariable-adjusted, propensity score-matched Cox proportional hazards regression models, relative to new users of warfarin, new users of DOACs tended to be at lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87) and all clinical fractures (HR, 0.93), whereas the association with hip fractures (HR, 0.91) was not statistically significant.


• When comparing individual DOACs with warfarin, the strongest findings were for apixaban (HR for hip fracture, 0.67; HR for fractures requiring hospitalization, 0.60; and HR for all clinical fractures, 0.86).


• In subgroup analyses, DOACs appeared more beneficial among patients with AF who also had a diagnosis of osteoporosis than among those without a diagnosis of osteoporosis.

"In 167 275 AF patients, the use of DOACs -- particularly apixaban -- versus warfarin was associated with a lower risk of fractures. These associations are more pronounced in patients with a diagnosis of osteoporosis," wrote the authors.

This study, titled “Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation,” is published in the journal JAMA Internal Medicine.

DOI: https://doi.org/10.1001/jamainternmed.2019.5679