Switching from Vitamin K Antagonists to Direct Oral Anticoagulants in Frail Elderly Patients with Atrial Fibrillation: Systematic Review and Meta-Analysis

Abstract

Background: Frailty complicates anticoagulation management in older patients with atrial fibrillation (AF), particularly when long-term vitamin K antagonist (VKA) therapy is already established. Whether switching to a direct oral anticoagulant (DOAC) improves outcomes in this setting remains uncertain, and guideline recommendations are limited. We performed a systematic review and meta-analysis comparing outcomes of VKA-to-DOAC switching versus VKA continuation in frail elderly patients with AF. Methods: MEDLINE, Scopus, and the Cochrane Library were systematically searched from inception through 4 April 2026. Studies enrolling frail elderly patients with AF receiving VKA therapy and directly comparing switching to a DOAC versus continued VKA treatment were eligible. The primary outcome was a composite of stroke/systemic embolism, major bleeding, or all-cause mortality. Adjusted hazard ratios (HRs) were pooled using three-level random-effects models. Results: Four studies (five treatment comparisons) comprising 57,099 patients were included. Overall, switching from VKA to DOAC therapy was not associated with a significant difference in the composite outcome compared with continued VKA treatment (HR 1.18, 95% CI 0.84–1.67). No significant differences were observed for major bleeding (HR 1.13, 95% CI 0.80–1.60), thromboembolism (HR 1.03, 95% CI 0.63–1.68), or all-cause mortality (HR 0.95, 95% CI 0.77–1.16). In analyses restricted to randomized trials, results remained neutral across all outcomes. Conclusion: In frail elderly patients with AF receiving VKA therapy, switching to a DOAC was not associated with significant reductions in thromboembolism, major bleeding, mortality, or the composite outcome compared with continued VKA treatment.