Oral anticoagulant therapy and outcomes in new-onset atrial fibrillation during acute myocardial infarction: A systematic review and meta-analysis

BACKGROUND New-onset atrial fibrillation (NOAF) is observed in 2%-21% of patients with acute myocardial infarction (AMI) and is associated with adverse outcomes, including increased mortality, heart failure, and stroke. Despite guideline recommendations the long-term role of oral anticoagulant (OAC) therapy in this population remains unclear. Most randomized clinical trials evaluating anticoagulation excluded patients with NOAF following AMI, creating a gap in high-quality evidence. Whether long-term OAC therapy improves prognosis without excess bleeding risk in this setting remains uncertain. We hypothesized that OAC use reduces mortality in patients with NOAF complicating AMI. AIM To determine the efficacy and safety of long-term OAC therapy in patients with NOAF during AMI. METHODS We conducted a systematic review of the PubMed and eLIBRARY databases through March 2025 following predefined patient, intervention, comparison, outcome criteria. Eligible observational studies included patients with AMI and newly detected atrial fibrillation during the index event who were prescribed OAC therapy with available outcome data. Methodological quality was evaluated using the Quality in Prognosis Studies tool. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Primary outcomes were all-cause mortality, ischemic stroke, and major bleeding. RESULTS Four studies including 7158 patients with a follow-up range of 1.0-8.6 years were analyzed. Long-term OAC therapy significantly reduced all-cause mortality (25.3% vs 33.6%; HR = 0.75; 95%CI: 0.64-0.90; P = 0.001) with no heterogeneity (I 2 = 0%). There was no significant reduction in ischemic stroke (3.5% vs 4.2%; HR = 0.82; 95%CI: 0.57-1.17; P = 0.26). Major or hospitalization-requiring bleeding was not increased (4.8% vs 4.1%; HR = 1.15; 95%CI: 0.89-1.47; P = 0.28). The cohorts largely reflected vitamin K antagonist-based therapy with clopidogrel. Stroke prevention benefit was not statistically significant, and data specific to direct OACs remain sparse. CONCLUSION Long-term OAC therapy after AMI with NOAF reduced mortality without consistent bleeding increase though findings mainly reflect warfarin-era practice and not direct OACs.