Oral anticoagulation with versus without antiplatelet therapy in patients with stable coronary artery disease and an indication for anticoagulation: a meta-analysis with trial sequential analysis

BACKGROUND: The optimal long-term antithrombotic strategy for patients with stable coronary artery disease (CAD) requiring oral anticoagulation (OAC) remains debated. Therefore, we conducted this meta-analysis to compare OAC monotherapy versus combination therapy (OAC plus a single antiplatelet agent) in this population. METHODS: A comprehensive literature search was conducted across major electronic databases for randomized controlled trials (RCTs) through December 2025. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Six RCTs (N = 5,924 patients) were included. OAC monotherapy significantly reduced the risk of major bleeding (RR, 0.49; 95% CI, 0.36-0.67), net adverse clinical events (RR, 0.63; 95% CI, 0.50-0.79), and cardiovascular death (RR, 0.72; 95% CI, 0.54-0.96) compared to combination therapy. While the overall incidence of major adverse cardiovascular events (MACE) was comparable (RR 0.83; 95% CI, 0.69-1.01), a pre-specified subgroup analysis by OAC type revealed a significant interaction (p-interaction = 0.01), showing MACE was significantly reduced with direct OAC (DOAC)-based monotherapy (RR 0.74; 95% CI, 0.61-0.89). CONCLUSION: In patients with stable CAD requiring OAC, OAC monotherapy significantly reduces bleeding and improves net clinical benefit without increasing ischemic risk. These findings support OAC monotherapy, particularly with DOACs, as the preferred long-term strategy, especially in East Asian populations.