Oral Anticoagulation With or Without Antiplatelet Therapy in Chronic Coronary Syndrome A Meta-Analysis of Randomized Trials

Background The optimal antithrombotic therapy for patients with chronic coronary syndrome (CCS) who also require long-term oral anticoagulation (OAC) remains uncertain. Objectives The aim of this study was to evaluate the safety and efficacy of OAC monotherapy compared with OAC plus single antiplatelet therapy (SAPT) in CCS patients with an indication for long-term anticoagulation. Methods Randomized trials comparing OAC monotherapy with OAC plus SAPT in patients with CCS and indication for long-term OAC from the PubMed, Cochrane Central, Web of Science, and Scopus databases up to November 10, 2025 were included in this systematic review and meta-analysis. HRs and 95% CIs were estimated through a random-effects meta-analytical framework. The primary efficacy endpoint was trial-defined major adverse cardiovascular events, and the primary safety endpoint was any bleeding. Results Six trials comprising 5,924 patients were included. The median follow-up duration was 2.3 years (Q1-Q3: 1.3-2.9 years), the median CHA2DS2-VASc score was 4.2 (Q1-Q3: 4.0-4.6), and the median time from revascularization to randomization 3.8 years (Q1-Q3: 3.2-4.4 years). Compared with OAC plus SAPT, OAC monotherapy showed similar rates of major adverse cardiovascular events (6.8% vs 8.2%; HR: 0.85; 95% CI: 0.64-1.09; I 2 =23%) and reduced risk of bleeding (8.9% vs 16.1%; HR: 0.49; 95% CI: 0.44-0.55; I 2 =8%). OAC monotherapy also reduced cardiovascular death (HR: 0.69; 95% CI: 0.48-0.97; I 2 =0%), net adverse clinical events (HR: 0.60; 95% CI: 0.47-0.78; I 2 =66%), and major bleeding (HR: 0.46; 95% CI: 0.32-0.66; I 2 =47%) compared with OAC plus SAPT. There were no significant differences in myocardial infarction, stroke, or all-cause mortality. Conclusions In patients with CCS requiring long-term OAC, OAC monotherapy was associated with reduced bleeding, cardiovascular death, and net adverse clinical events compared with OAC plus SAPT. (Anticoagulation Alone vs Anticoagulation Plus Antiplatelet Therapy in Atrial Fibrillation With Stable Coronary Disease: A Meta-Analysis of Randomized Trials; CRD420251174643).