Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation.
The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown.



To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF.



Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016.



Dabigatran or warfarin use during the study period.



Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated.



Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 [95% CI, -0.38 to -0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 [95% CI, -2.40 to -3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 [95% CI, 0.67 to -0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, <.001).



Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Wallis C Y
WC
Lau
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Esther W
EW
Chan
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China2Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Ching-Lung
CL
Cheung
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Chor Wing
CW
Sing
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China3Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Kenneth K C
KK
Man
University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom5Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Gregory Y H
GY
Lip
Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
Chung-Wah
CW
Siu
Osteoporosis Centre, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
Joanne K Y
JK
Lam
Osteoporosis Centre, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
Alan C H
AC
Lee
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China8Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom.
Ian C K
IC
Wong
D000058:Accidental Falls / Q000706:statistics & numerical data; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D000991:Antithrombins / Q000009:adverse effects; D001281:Atrial Fibrillation; D000069604:Dabigatran / Q000009:adverse effects*; D016208:Databases, Factual; D005260:Female; D006620:Hip Fractures / Q000139:chemically induced / Q000453:epidemiology; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D008297:Male; D058866:Osteoporotic Fractures / Q000139:chemically induced* / Q000453:epidemiology; D016012:Poisson Distribution; D057216:Propensity Score; D012189:Retrospective Studies; D012306:Risk; D016103:Spinal Fractures / Q000139:chemically induced / Q000453:epidemiology; D020521:Stroke / Q000517:prevention & control; D014859:Warfarin / Q000009:adverse effects*
D000925:Anticoagulants; D000991:Antithrombins; D014859:Warfarin; D000069604:Dabigatran