Oral Anticoagulant Monotherapy vs. Combination Therapy in Chronic Coronary Syndrome Requiring Long-Term Anticoagulation: An Updated Meta-Analysis of Randomized Controlled Trials

Introduction Evidence surrounding the optimal antithrombotic regimen for patients with chronic coronary syndrome (CCS) requiring oral anticoagulation remains scarce. This meta-analysis evaluates the efficacy and safety of oral anticoagulant (OAC) monotherapy compared to OAC plus single antiplatelet therapy (SAPT) in this population. Methods We systematically searched for randomized controlled trials (RCTs) till February 2026 comparing OAC monotherapy versus OAC plus SAPT in patients with CCS. Primary outcomes included major or clinically relevant non-major bleeding, net adverse clinical events (NACE), all-cause mortality, and cardiovascular (CV) deaths. Pooled risk ratios (RR) with 95% confidence intervals (CIs) were calculated. Results OAC monotherapy was associated with a significantly lower risk of major or clinically relevant non-major bleeding compared with dual antithrombotic therapy (DAT) (RR: 0.50; 95% CI: 0.38–0.65; p < 0.001; I 2 = 42%). Similarly, OAC monotherapy significantly reduced the incidence of NACE (RR: 0.64; 95% CI: 0.50–0.81; p < 0.001; I 2 = 64%). There was no significant difference between the two strategies in all-cause mortality (RR: 0.79; 95% CI: 0.55–1.13; p = 0.20; I 2 = 52%). However, OAC monotherapy was associated with a significantly lower risk of CV mortality (RR: 0.71; 95% CI: 0.53–0.97; p = 0.03; I 2 = 3%). Conclusion In patients with CCS requiring long-term oral anticoagulation, OAC monotherapy significantly reduced major or clinically relevant non-major bleeding, CV mortality, and NACE compared with dual antithrombotic therapy (DAT). Rates of major ischemic events, Myocardial Infarction, stroke, and all-cause mortality were comparable between the two strategies.