Antiplatelet therapy in patients with chronic coronary syndrome requiring oral anticoagulation: An updated meta-analysis of randomized trials.

BACKGROUND

Patients with chronic coronary syndrome (CCS) often require long-term oral anticoagulation (OAC), most commonly for atrial fibrillation (AF). Evidence on the optimal antithrombotic strategy in this setting remains inconclusive, prompting this updated meta-analysis of randomized trials comparing OAC plus a single antiplatelet therapy (SAPT) with OAC monotherapy.

METHODS

We systematically searched PubMed/MEDLINE, SciELO, Latindex, LILACS, the Cochrane Library, and ClinicalTrials.gov up to November 12, 2025. The primary efficacy endpoint was all-cause death, while secondary efficacy endpoints included cardiovascular death, acute myocardial infarction, ischemic stroke, and systemic embolism, each analyzed individually. Safety endpoints comprised major and clinically relevant non-major bleeding (International Society on Thrombosis and Hemostasis [ISTH] definition).

RESULTS

Six randomized trials including 5,924 participants were analyzed. All-cause death did not differ significantly between OAC plus SAPT and OAC monotherapy (OR 1.31; 95 % CI 0.89-1.92). Dual therapy was associated with an increased risk of cardiovascular death (OR 1.42; 95 % CI 1.05-1.92), whereas rates of myocardial infarction (OR 0.98; 95 % CI 0.60-1.57), ischemic stroke (OR 0.95; 95 % CI 0.64-1.39), and systemic embolism (OR 1.00; 95 % CI 0.20-4.95) were similar between groups. Safety outcomes were markedly worse with dual therapy, which significantly increased the risk of major bleeding (OR 2.20; 95 % CI 1.51-3.22) and major or clinically relevant non-major bleeding (OR 2.30; 95 % CI 1.72-3.06).

CONCLUSIONS

In patients with CCS requiring long-term OAC, dual therapy (OAC plus SAPT) did not reduce all-cause death nor ischemic events compared with OAC alone but significantly increased major bleeding and cardiovascular death. PROSPERO Registration No.: CRD420251239917.