Warfarin Use Associated with Increased Risk of Fractures Compared to DOACs


A new study from the University of Minnesota is shedding light on the potentially adverse impact warfarin use can have on bone health compared to DOAC therapies in patients with atrial fibrillation.

doctor examining leg

While previous research has indicated its association with adverse events, new data is suggesting use of warfarin in patients with atrial fibrillation (AF) could negatively impact a patient’s bone health.

An analysis from the University of Minnesota that examined more than 150,000 patients found use of warfarin was associated with increased risk of clinical fractures and fractures requiring hospitalizations when compared to newer direct oral anticoagulant (DOAC) therapies.

In order to determine whether warfarin use adversely impacts bone health, investigators 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. In total, 167, 275 patients were included in the study—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 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.

Cox proportional hazards regression models revealed new users of DOACs tended to be at lower risk of fractures requiring hospitalization (HR, 0.87; 95% CI, 0.79-0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88-0.98). Investigators noted an association was present, but not statistically significant when examining hip fractures (HR, 0.91; 95% CI, 0.78-1.07).

In analyses comparing individual DOACs to warfarin, investigators observed the strongest associations for apixaban across all outcomes examined (Hip fracture HR, 0.67 95% CI, 0.45-0.98; Fractures requiring hospitalization, HR, 0.60 95% CI, 0.47-0.78; All clinical fractures HR, 0.86 95% CI, 0.75-0.98). Additionally, subgroup analyses indicated greater benefit among patients with AF with osteoporosis than among those without osteoporosis.

Investigators argue the results of the current analysis—combined with data from previous research—highlight the need for clinicians to exercise caution when prescribing warfarin over newer DOACs for anticoagulation.

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

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

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