Oral anticoagulation with versus without antiplatelet therapy in patients with stable chronic coronary disease: 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. The incidence of major adverse cardiovascular events (MACE) was comparable between groups overall (RR 0.83, 95% CI 0.69-1.01). However, 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. Conclusion: In patients with stable CAD, OAC monotherapy significantly reduces bleeding and improves net clinical benefit without increasing ischemic risk. These findings support OAC monotherapy, particularly with a DOAC, as the preferred long-term strategy, especially in East Asian populations.