A Network Meta-Analysis Comparing Osteoporotic Fracture among Different Direct Oral Anticoagulants and Vitamin K Antagonists in Patients with Atrial Fibrillation

BACKGROUND: There are limited studies comparing the risk of osteoporosis and fractures between different direct oral anticoagulants (DOACs) and vitamin K antagonists (VKA) in non-valvular atrial fibrillation (AF). Using a network meta-analysis (NMA), we compared osteoporotic fractures among 5 different treatment arms, viz. dabigatran, rivaroxaban, apixaban, edoxaban, and VKA. METHODS: Ten studies, including 5 randomized control trials and 5 population-based studies, with a total of 321,844 patients (148,751 and 173,093 in the VKA and DOAC group, respectively) with a median follow-up of 2 years, were included. A Bayesian random-effects NMA model comparing fractures among the treatment arms was performed using MetInsight V3. Sensitivity analysis excluded studies with the highest residual deviances from the NMA model. RESULTS: The mean age of the patients was 70 years. The meta-analysis favored DOACs over VKA with significantly lower osteoporotic fracture (odds ratio [OR], 0.77; 95% credible interval [CrI], 0.70–0.86). The NMA demonstrated that fractures were significantly lower with apixaban compared with dabigatran (OR, 0.64; 95% CrI, 0.44–0.95); however, fractures were statistically similar between apixaban and rivaroxaban (OR, 0.84; 95% CrI, 0.58–1.24) and dabigatran and rivaroxaban (OR, 1.32; 95% CrI, 0.90–1.87). Based on the Bayesian model of NMA, the probability of osteoporotic fracture was highest with VKA and lowest with apixaban, followed by rivaroxaban, edoxaban, and dabigatran. CONCLUSIONS: The decision to prescribe anticoagulants in elderly patients with AF should be made not only based on thrombotic and bleeding risks but also on the risk of osteoporotic fracture; these factors should be considered and incorporated in contemporary cardiology practice.