Warfarin versus Alternate Direct Oral Anticoagulants: Fracture Risk in AF Patients

A new study evaluated the risk of fracture among nonvalvular atrial fibrillation (AF) patients taking warfarin versus alternate direct oral anticoagulants.

“Warfarin is prescribed to patients with atrial fibrillation (AF) for the prevention of cardioembolic complications. Whether warfarin adversely affects bone health is controversial. The availability of alternate direct oral anticoagulant (DOAC) options now make it possible to evaluate the comparative safety of warfarin in association with fracture risk,” established the researchers, whose study was published in JAMA Internal Medicine.

This was a comparative effectiveness cohort study in which researchers queried the MarketScan administrative claims databases for data on nonvalvular AF patients prescribed oral anticoagulants between Jan. 1, 2010, and Sept. 30, 2015. Patients were matched by age, sex, CHA₂DS₂-VASc (congestive heart failure, hypertension, age [>65 years = 1 point; >75 years = 2 points], diabetes, and previous stroke/transient ischemic attack [2 points], vascular disease) score, and high-dimensional propensity scores. The exposures were warfarin and direct oral anticoagulants including dabigatran etexilate, rivaroxaban, and apixaban. The primary outcome measures were incident hip fracture, fracture requiring hospitalization, and all clinical fractures per International Classification of Diseases, Ninth Revision, Clinical Modification codes.

Final analysis included 167,275 AF patients (mean [SD] age, 68.9 [12.5] years; 62% were male). Mean (SD) follow-up was 16.9 (13.7) months, during which time 817 hip fractures, 2,013 hospitalized fractures, and 7,294 total fractures were recorded. In multivariable-adjusted analyses, new direct oral anticoagulant users, compared to new warfarin users, had a lower risk of fractures requiring hospitalization (hazard ratio [HR], 0.87; 95% CI, 0.79 to 0.96) and all clinical fractures (HR, 0.93; 95% CI, 0.88 to 0.98); there was not a significant association regarding hip fractures (HR, 0.91; 95% CI, 0.78 to 1.07). Specifically, among the direct oral anticoagulants, the most significant correlations were observed in apixaban (HR for hip fracture, 0.67 [95% CI, 0.45 to 0.98]; HR for fractures requiring hospitalization, 0.60 [95% CI, 0.47 to 0.78]; and HR for all clinical fractures, 0.86 [95% CI, 0.75 to 0.98]). Subgroup analyses revealed a greater benefit among AF patients with a concurrent osteoporosis diagnosis compared to non-osteoporosis patients.

“In this real-world population of 167 275 patients with AF, use of [direct oral anticoagulants]—particularly apixaban—compared with warfarin use was associated with lower fracture risk. These associations were more pronounced among patients with a diagnosis of osteoporosis. Given the potential adverse effects of warfarin on bone health, these findings suggest that caution should be used when prescribing warfarin to patients with AF at high risk of fracture,” concluded the study authors.