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Fracture Risk Higher With Warfarin vs DOACs

November 26, 2019

By Megan Brooks

NEW YORK (Reuters Health) - Warfarin is associated with an increased risk of fractures compared with a direct oral anticoagulant (DOAC), a large real-world analysis has found.

"This study adds to the growing body of evidence suggesting that warfarin has an adverse effect on bone health. Caution should be used when prescribing warfarin to atrial fibrillation (AF) patients at elevated fracture risk," first author Dr. Pamela Lutsey of the University of Minnesota School of Public Health in Minneapolis told Reuters Health by email.

The study was published online November 25 in JAMA Internal Medicine.

Using the MarketScan claims database, the research team evaluated the comparative safety of warfarin versus DOACs in association with fracture risk in more than 167,000 patients (mean age, 69; 62% men) with nonvalvular AF prescribed oral anticoagulants over nearly six years.

Forty-nine percent of patients were treated with warfarin and the remainder with a DOAC (11% received apixaban, 19% dabigatran and 21% rivaroxaban).

During an average follow up of 16.9 months, there were 817 hip fractures, 2,013 fractures requiring hospitalization and 7,294 clinical fractures (identified using inpatient and outpatient claims).

In multivariable-adjusted, propensity-score-matched Cox proportional hazards regression models, new users of a DOAC were at lower risk of fractures requiring hospitalization (hazard ratio, 0.87; 95% confidence interval, 0.79 to 0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88 to 0.98), compared with new users of warfarin.

There was also a lower risk in DOAC users versus warfarin users for hip fracture that did not reach statistical significance (HR, 0.91; CI 0.78 to 1.07), but the precision was poorer for this outcome, the authors note.

"In general," they add, "associations were more pronounced among patients with AF with a diagnosis of osteoporosis relative to those without. The strongest effect estimates were observed when comparing apixaban and warfarin; this finding was not hypothesized and, as such, warrants further scrutiny. We found no apparent differences in fracture risk in head-to-head DOAC comparisons. Collectively, our findings support the notion that warfarin may be harmful to bone health."

Dr. Lutsey and colleagues say their findings are consistent with a recent study from Hong Kong that found greater fracture risk with use of warfarin than dabigatran in patients with AF (

"It is imperative to treat the whole patient. As such, it is important to optimize AF management therapies to avoid unintended adverse consequences, such as fracture," Dr. Lutsey told Reuters Health by email.

The study had no commercial funding and the authors have no relevant disclosures.


JAMA Intern Med 2019.

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