Fracture risks in patients with atrial fibrillation treated with different oral anticoagulants: a meta-analysis and systematic review

AIMS: evidence on the difference in fracture risks for patients with atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs) versus warfarin remains controversial. We aim to compare the fracture risks between the DOAC and warfarin prescriptions among the AF patients. METHODS AND RESULTS: we systematically searched PubMed, EMBASE, the Cochrane Library and Web of Science up to 19 April 2021 for relevant studies. And the observational studies regarding the relationship between the DAOC versus warfarin prescriptions and fracture risks among the patients with AF were included in this meta-analysis. Two investigators independently screened the articles and extracted the relevant data. A random- or fixed-effect model was applied to calculate the pooled hazard ratio/relative ratios with 95% confidence intervals of fracture risks associated with the DOAC and warfarin prescriptions. Six studies comprising 351,208 patients and 9,424 fractures were included in this meta-analysis. Overall, the AF patients treated with DOACs tend to present a lower risk of any fracture compared with those treated with warfarin (relative ratio: 0.82, 95% confidence interval (CI): 0.74–0.91). Sub-analyses for each individual DOAC indicate that apixaban and rivaroxan are associated with lower risk of any fracture compared with warfarin (HR: 0.75, 95% CI: 0.60–0.92, and HR: 0.79, 95% CI: 0.71–0.88, respectively). CONCLUSION: this meta-analysis suggests that DOAC users have a lower risk of fractures than the warfarin users. The results of this study may provide optimal anticoagulation opportunities for AF patients with high fracture risk factors.