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

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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

Yang et al., 2023 | Acta Cardiol | Meta Analysis

Citation

Yang Nana, Zhao Ying, ... Cheng Gang. 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. Acta Cardiol. 2023-May;78(3):298-310. doi:10.1080/00015385.2022.2030555

Abstract

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.

Key Findings

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

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population atrial fibrillation
Sample Size 477821
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Aged
  • Warfarin
  • Anticoagulants
  • Atrial Fibrillation
  • Rivaroxaban
  • Dabigatran
  • Osteoporotic Fractures
  • Administration, Oral
  • Stroke

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Meta-Analysis, Systematic Review, Journal Article
  • Vertical: vitamin-k

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09