Na He1,2,3, Sophie Dell'Aniello2, Suodi Zhai1, Samy Suissa2,3, Christel Renoux2,3,4. 1. Department of Pharmacy, Peking University Third Hospital, 49 Huayuan North Road, Beijing 100191, China. 2. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine Road, Montreal, Québec H3T 1E2, Canada. 3. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Québec H3A 1A2, Canada. 4. Department of Neurology and Neurosurgery, McGill University, 853 Sherbrooke Street West, Montreal, Québec H3A 0G5, Canada.
Abstract
AIMS: To determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF), accounting for cumulative duration of use. METHODS AND RESULTS: Using Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10 306 new users of DOACs and 15 357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture [crude incidence rates 7.5 vs. 15.3 per 1000 person-years; adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.46-0.91] compared to VKA duration ≥180 days. Direct oral anticoagulants use was also associated with a lower risk of hip fracture (HR 0.51, 95% CI 0.31-0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95% CI 0.79-1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls. CONCLUSION: Prolonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF. Published on behalf of the European Society of Cardiology.
AIMS: To determine the risk of fracture associated with direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF), accounting for cumulative duration of use. METHODS AND RESULTS: Using Quebec administrative healthcare databases, we formed a cohort of all patients aged 40 years or older newly diagnosed with NVAF, who filled a first prescription for DOACs or VKAs between 2011 and 2014. Exposure was modelled as a time-varying variable whereby patients were considered unexposed up to 180 days of cumulative duration of use (to account for a biologically meaningful exposure) and exposed thereafter. The final cohort included 10 306 new users of DOACs and 15 357 new users of VKAs. After propensity score-based fine stratification and weighting, use of DOACs for 180 days or greater was associated with a 35% decreased risk of fracture [crude incidence rates 7.5 vs. 15.3 per 1000 person-years; adjusted hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.46-0.91] compared to VKA duration ≥180 days. Direct oral anticoagulants use was also associated with a lower risk of hip fracture (HR 0.51, 95% CI 0.31-0.86) compared with VKAs. There was no difference in the rate of fracture for shorter duration of use (HR 1.10; 95% CI 0.79-1.53). The risk was not modified by age, sex, chronic kidney disease, osteoporosis, history of fracture or falls. CONCLUSION: Prolonged use of DOACs is associated with a lower risk of fracture compared with VKAs. These findings support the first-line recommendation for DOACs in patients with NVAF. Published on behalf of the European Society of Cardiology.
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