The association of non-vitamin K antagonist oral anticoagulants vs. warfarin and the risk of fractures for patients with atrial fibrillation: a systematic review and meta-analysis

Background The fracture risks of non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin in patients with atrial fibrillation (AF) remain controversial. Methods PubMed, Cochrane Library, EMBASE, Clinical Trials.gov databases for RCTs, and cohort studies were systematically searched from inception to 10 June 2021. Results Twelve-two studies met the inclusion criteria and 477,821 patients were included. Warfarin increased the risk of fracture in AF patients compared with NOACs in overall any fracture (RR = 0.79; 95% CI = 0.70-10.88; p = 0.00), osteoporotic fracture (RR = 0.746; 95% CI = 0.630-0.883; p = 0.001). No significant difference was observed in the hip or pelvic fracture, vertebral fracture, extremity fracture, wrist fracture, femoral neck fracture, and ankle fracture. In subgroup analyses based on several aspects, NOACs were associated with a significant reduction in any fracture (standard dosage NOACs, cohort studies, elderly patients, rivaroxaban in RCTs, dabigatran, rivaroxaban, and apixaban in cohort studies), in the hip/pelvic fracture (follow-up time <= 1 year, cohort studies), and osteoporotic fracture (cohort studies). Conclusion NOACs were associated with a significantly lower risk of any fracture and osteoporotic fracture compared to warfarin. This benefit was also observed in specific NOACs types of dabigatran, rivaroxaban, and apixaban. However, whether NOACs had a less fracture risk than warfarin on the other risk of fractures was still uncertain.