Abstract
Background: Current evidence regarding the application of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) on the fracture risk is inconsistent. Therefore, we conducted a meta-analysis to evaluate the fracture risk of DOACs vs. VKAs in patients with atrial fibrillation (AF).Methods: The PubMed and Embase databases were systematically searched until June 2021 for all the studies that reported oral anticoagulants in AF patients. The random-effect model with an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs).Results: A total of 10 studies were included in this meta-analysis. Among AF patients receiving anticoagulants, DOAC users showed a reduced risk of any fracture compared to those with VKAs (RR = 0.80; 95% CI: 0.70–0.91) regardless of gender [males (RR = 0.79; 95% CI: 0.67–0.92) and females (RR = 0.71; 95% CI: 0.57–0.89)]. Apixaban (RR = 0.75; 95% CI: 0.60–0.92) and rivaroxaban (RR = 0.73; 95% CI: 0.61–0.88), but not dabigatran and edoxaban, were associated with a decreased risk of any fracture compared with VKAs. DOAC users had decreased risks of osteoporotic fractures (RR = 0.63; 95% CI: 0.47–0.84) and hip/pelvic fractures (RR = 0.88; 95% CI: 0.79–0.97) compared to those treated with VKAs.Conclusions: Our meta-analysis suggested that the use of DOACs was associated with a reduced risk of any fracture compared with VKAs. Further studies should confirm our findings.
Highlights
Atrial fibrillation (AF) is becoming an aging-related disease, and osteoporotic fractures are major health threats in the elderly
Among AF patients receiving anticoagulants, direct oral anticoagulants (DOACs) users showed a reduced risk of any fracture compared to those with Vitamin K antagonists (VKAs) (RR = 0.80; 95% confidence intervals (CIs): 0.70–0.91) regardless of gender [males (RR = 0.79; 95% CI: 0.67–0.92) and females (RR = 0.71; 95% CI: 0.57–0.89)]
Apixaban (RR = 0.75; 95% CI: 0.60–0.92) and rivaroxaban (RR = 0.73; 95% CI: 0.61–0.88), but not dabigatran and edoxaban, were associated with a decreased risk of any fracture compared with VKAs
Summary
Atrial fibrillation (AF) is becoming an aging-related disease, and osteoporotic fractures are major health threats in the elderly. Vitamin K antagonists (VKAs) such as warfarin has been speculated to increase the risk of osteoporotic fracture. Warfarin inhibits the γ-carboxylation of several osteoblastspecific proteins [1, 2], leading to low bone density and increased fracture risk [3]. These observations propose a link between warfarin use and the risk of osteoporotic fractures [4, 5]. Current evidence regarding the application of direct oral anticoagulants (DOACs) vs vitamin K antagonists (VKAs) on the fracture risk is inconsistent. We conducted a meta-analysis to evaluate the fracture risk of DOACs vs VKAs in patients with atrial fibrillation (AF)
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