Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation | Atrial Fibrillation | JAMA | JAMA Network
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Original Investigation
March 21, 2017

Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation

Wallis C. Y. Lau, BSc1; Esther W. Chan, PhD1; Ching-Lung Cheung, PhD1,2; et al Chor Wing Sing, BSc1; Kenneth K. C. Man, MPH1,3; Gregory Y. H. Lip, MD4,5; Chung-Wah Siu, MD6; Joanne K. Y. Lam, FHKAM7; Alan C. H. Lee, FHKAM7; Ian C. K. Wong, PhD1,8
Author Affiliations Article Information
  • 1Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • 2Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • 3Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
  • 4University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom
  • 5Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  • 6Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
  • 7Osteoporosis Centre, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China
  • 8Research Department of Practice and Policy, UCL School of Pharmacy, London, United Kingdom
JAMA. 2017;317(11):1151-1158. doi:10.1001/jama.2017.1363
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Key Points

Question  What is the risk of osteoporotic fracture associated with the use of dabigatran compared with warfarin among patients with nonvalvular atrial fibrillation (NVAF)?

Findings  In this population-based cohort study of 8152 patients, use of dabigatran was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (incidence, 0.7 vs 1.1 per 100 person-years) during a mean follow-up of approximately 500 days.

Meaning  Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture; further studies may be warranted to assess this further.

Abstract

Importance  The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown.

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

Design, Setting, and Participants  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.

Exposures  Dabigatran or warfarin use during the study period.

Main Outcomes and Measures  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.

Results  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).

Conclusions and Relevance  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.

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