Warfarin use and risk of osteoporotic fractures
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OBJECTIVE: Prior studies examining the association of warfarin use and osteoporotic fractures have found conflicting results and have had methodological problems, such as confounding by indication and confounding by duration of warfarin use. Thus, we studied the association of warfarin use with fractures at the hip, spine and wrist, among older men and women with atrial fibrillation recruited from the general population, using rigorous statistical tools to overcome challenges faced by prior studies. METHODS: We included men and women ≥65 years with incident atrial fibrillation, without history of fracture, followed between 2000-2010 from The Health Improvement Network (THIN). Long-term warfarin use was defined in two ways: 1) warfarin use ≥ 1year; 2) warfarin use ≥3 years. Non-use was defined as no use of warfarin over the follow-up period. Propensity scores (PS) for warfarin use were calculated using logistic regression with long-term use of warfarin as the dependent variable and age, sex, body mass index (BMI), history of multiple falls, deep venous thrombosis, pulmonary embolism, heart failure, neuropsychiatric impairment, hyperthyroidism, estrogen use, beta blockers, corticosteroids, bisphosphonates, smoking and alcoholism as independent variables. Each warfarin user was then matched by PS to a non-user by the “greedy matching” method. Incidence rates were calculated for warfarin users and non-users. The association between long-term warfarin use and risk of hip, spine and wrist fractures was evaluated using Cox-proportional hazards models. RESULTS: Incidence rates of hip fracture were 5.21 and 6.20 per 1000 person-years among subjects with warfarin use >1 (n=20,346) and >3 (n=11,238) years, respectively. The hazard ratios of hip fracture for warfarin use >1 and >3 years were 1.08 (95% CI 0.87, 1.35) and 1.13 (95% CI: 0.84, 1.5), respectively. Similar findings were observed between warfarin use and risk of spine or wrist fracture. CONCLUSIONS: Long-term use of warfarin among older adults with atrial fibrillation is not associated with increased risk of osteoporotic fractures and thus, does not necessitate additional surveillance or prophylaxis.
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