Oral Anticoagulant Monotherapy Versus Combination Therapy in Patients With Chronic Coronary Syndrome: A Systematic Review and Meta-analysis of Randomized Trials

AIMS: In patients on long-term oral anticoagulation (OAC), the optimal antithrombotic strategy in the setting of concomitant chronic coronary syndrome (CCS) remains unclear. We therefore performed a systematic review and meta-analysis of randomized controlled trials comparing OAC monotherapy versus OAC plus single antiplatelet therapy (combination therapy) in patients with CCS and any indication for long-term OAC..

METHODS: We systematically searched PubMed/MEDLINE and Embase through February 2026 to identify trials randomizing CCS patients with an indication for long-term OAC to OAC monotherapy vs. combination therapy. Net adverse clinical events (NACE) were defined as primary composite endpoint. Key secondary outcomes included major adverse cardiovascular events (MACE), major bleeding, and major or clinically relevant non-major bleeding. Hazard ratios (HRs) were pooled using Bayesian random-effects models.

RESULTS: Six (6) randomized trials met the inclusion criteria. Five (5) contributed to quantitative synthesis of primary and main secondary outcome measures (5,777 participants). OAC monotherapy significantly reduced NACE (HR 0.61, 95% CrI 0.43-0.85), major bleeding (HR 0.47, 95% CrI 0.30-0.71) and major or clinically relevant non-major bleeding (HR 0.47, 95% CrI 0.31-0.66) compared to combination therapy. No significant differences were observed for MACE (HR 0.83, 95% CrI 0.60-1.18), cardiovascular death (HR 0.70, 95% CrI 0.44-1.13), all-cause death, unplanned revascularisation, myocardial infarction and ischemic stroke. Prespecified subgroup analyses for NACE and MACE outcomes detected a signal of lower risk of MACE with direct oral anticoagulant monotherapy compared to monotherapy with vitamin K antagonists (p=0.02).

CONCLUSIONS: In CCS patients on OAC, OAC monotherapy reduces bleeding events compared to combination therapy, without clear evidence of a concomitant increase in ischemic risk.