Abstract TP116: Comparative Effectiveness of Direct Oral Anticoagulants Among Patients with Clinical Versus Subclinical Atrial Fibrillation: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Atrial fibrillation (AF) increases the risk of ischemic stroke. While direct oral anticoagulants (DOACs) reduce stroke risk in clinical AF, the benefit-risk profile in subclinical AF, detected by implantable cardiac devices, remains uncertain. We performed a systematic review and meta-analysis of randomized trials to compare the effectiveness of DOACs versus no oral anticoagulants (OACs) in clinical and subclinical AF. Methods: We searched PubMed, EMBASE, and CENTRAL from January 1, 2000, to June 9, 2025 for randomized controlled trials comparing DOACs with placebo or antiplatelet therapy in patients with clinical or subclinical AF. The primary outcome was ischemic stroke. Secondary outcomes included stroke, systemic embolism, death, and bleeding. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using fixed-effects models. Results: Four trials (n=13,131) were included. DOACs reduced ischemic stroke in clinical AF (RR 0.35, 95% CI 0.26–0.49; number needed to treat in 1.2 years, 38) and subclinical AF (RR 0.68, 95% CI 0.50–0.92; number needed to treat in 1.6 years, 104), with a greater benefit in clinical AF (p=0.004 for interaction). Similar patterns were seen for other thromboembolic outcomes. Major bleeding was increased in subclinical AF (RR 1.53, 95% CI 1.20–1.95; number needed to harm in 1.6 years, 60) but not in clinical AF (p=0.41 for interaction). No significant differences were observed in intracranial or fatal bleeding. Conclusions: DOACs provide a greater net clinical benefit in patients with clinical AF compared to subclinical AF. In subclinical AF, modest stroke risk reduction must be weighed against increased bleeding risk.