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Purpose:  There is uncertainty as to which anticoagulant should be used in non-valvular atrial fibrillation (AF) with valvular heart disease. This systematic review and meta-analysis aimed to assess the efficacy and safety of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular AF with valvular heart disease.   Methods:  We performed a comprehensive literature search using PubMed, Scopus, Embase, and Clinicaltrials.gov from the inception of databases up until August 2, 2021, and the search was updated and finalized on October 17, 2021. The intervention group was DOACs and the control group was warfarin. The primary outcome was systemic embolism and stroke (SSE), and the secondary outcome was major bleeding and intracranial hemorrhage. The pooled effect estimate was reported as the hazard ratio (HR) and odds ratio (OR).   Results:  There were 21,185 patients from seven studies included in this systematic review and meta-analysis. Stroke and systemic embolism were lower in patients receiving DOACs [HR 0.76 (95% CI 0.67, 0.87),  p  &amp;lt; 0.001; I 2 : 5%] compared with warfarin. The subgroup analysis on RCTs showed the significant reduction of SSE in the DOACs group [HR 0.73 (95% CI 0.60, 0.89),  p  = 0.002; I 2 : 16%]. There was no significant difference in terms of major bleeding [HR 0.89 (95% CI 0.75, 1.05),  p  = 0.18; I 2 : 69%]. Intracranial hemorrhage [HR 0.42 (95% CI 0.22, 0.80),  p  = 0.008; I 2 : 73%] were lower in the DOAC group.   Conclusion:  This meta-analysis indicates that DOACs were associated with a lower risk of SSE and intracranial hemorrhage compared with patients receiving warfarin. There was no significant difference between the two groups in terms of major bleeding.

frontiers in cardiovascular medicine

Direct Acting Oral Anticoagulant vs. Warfarin in the Prevention of Thromboembolism in Patients With Non-valvular Atrial Fibrillation With Valvular Heart Disease—A Systematic Review and Meta-Analysis