• Lau Wallis C Y WCY UCL School of Pharmacy, London, United Kingdom, and Centre for Safe Medication and Practice Research, The University of Hong Kong, Hong Kong, China (W., Ching-Lung Cheung, Man Kenneth K C KKC UCL School of Pharmacy, London, United Kingdom, and Centre for Safe Medication and Practice Research, The University of Hong Kong, Hong Kong, China (W, Esther W Chan, Chor Wing Sing, Lip Gregory Y H GYH Liverpool Centre for Cardiovascular Science, University of Liverpool, and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom, and Aalborg T, Chung-Wah Siu, Lam Joanne K Y JKY Osteoporosis Centre, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China (J.K.L., A.C.L.)., Lee Alan C H ACH Osteoporosis Centre, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China (J.K.L., A.C.L.)., and Wong Ian C K ICK UCL School of Pharmacy, London, United Kingdom, Centre for Safe Medication and Practice Research, The University of Hong Kong, Hong Kong, and The Univers.
• UCL School of Pharmacy, London, United Kingdom, and Centre for Safe Medication and Practice Research, The University of Hong Kong, Hong Kong, China (W.C.L., K.K.M.).
• Ann. Intern. Med. 2020 Jul 7; 173 (1): 1-9.

BackgroundIt is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF).ObjectiveTo compare the risk for osteoporotic fracture between anticoagulants.DesignPopulation-based cohort study.SettingTerritory-wide electronic health record database of the Hong Kong Hospital Authority.ParticipantsPatients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018.MeasurementsOsteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score-weighted cumulative incidence differences (CIDs).ResultsThere were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, -0.88% [95% CI, -1.66% to -0.21%]; dabigatran CID, -0.81% [CI, -1.34% to -0.23%]; and rivaroxaban CID, -1.13% [CI, -1.67% to -0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, -0.06% [CI, -0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, -0.32% [CI, -0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, -0.25% [CI, -0.86% to 0.40%]).LimitationResidual confounding is possible.ConclusionAmong patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit-risk assessment when choosing between anticoagulants.Primary Funding SourceThe University of Hong Kong and University College London Strategic Partnership Fund.

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