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; I2 = 42%). Similarly, OAC monotherapy significantly reduced the incidence of NACE (RR: 0.64; 95% CI: 0.50–0.81; p < 0.001; I2 = 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; I2 = 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; I2 = 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.