Association of Anticoagulant Therapy With Risk of Fracture Among Patients With Atrial Fibrillation

1. Direct oral anticoagulants, specifically apixaban, were associated with lower risk of fracture in patients with atrial fibrillation compared to warfarin.

Evidence Rating Level: 2 (Good)

Warfarin is commonly used to prevent cardioembolic events in individuals with atrial fibrillation (AF). The impact of warfarin treatment on bone health is clinically important, particularly in those susceptible to bone fractures due to falls and other events. With the advent and approval of direct oral anticoagulants (DOACs), the safety and efficacy of these medications can be investigated to clarify this controversy in individuals with nonvalvular AF, specifically in terms of future fractures and fracture-related hospitalizations. The objective of this prospective cohort study was to examine the effect of DOACs versus warfarin in terms of risk of incident fractures in individuals with non-valvular AF. Using MarketScan administrative claims data from 167,275 individuals with AF between January 2010 and September 30, 2015, new DOAC users were matched to up to three warfarin-only new users. Participants were matched by propensity score using Cox proportional hazards regression models to compare warfarin and DOAC groups. Outcomes of interest were hip fractures, fractures requiring hospitalization and all clinical fractures. Overall, new users of DOACs were found to be at decreased risk of fracture-related hospitalizations (HR 0.87, 95% CI 0.79 to 0.96) and overall fractures (HR 0.93, 95% CI 0.88 to 0.98) compared to new users of warfarin. The difference in incidences of hip fractures across groups was not significant. Of all DOACs, apixaban resulted in the most significant differences compared to warfarin, with reduced hip fractures (HR 0.67, 95% CI 0.45 to 0.98), fracture-related hospitalizations (HR 0.60, 95% CI 0.47 to 0.78), and overall fractures (HR 0.86, 95% CI 0.75 to 0.98). Subgroup analyses found that DOAC-related hip fractures in individuals with AF were lower in those with suspected osteoporosis (HR 0.74, 95% CI 0.58 to 0.96) compared to those without (HR 1.06, 95% CI 1.06, 0.86 to 1.30), with similar findings when analyzing fracture-related hospitalizations. Therefore, DOAC use, particularly apixaban, was found to be associated with reduced incidences of fractures and fracture-related hospitalizations compared to warfarin, with potential additive benefits for those with comorbid osteoporosis.

Click to read the study in JAMA Internal Medicine

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