Comparative Effectiveness and Safety of Non–Vitamin K Antagonist Oral Anticoagulant-based Triple Therapy versus Dual Antiplatelet Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Background: Atrial fibrillation (AF) increases thromboembolic and cardiovascular risks. In patients with AF undergoing percutaneous coronary intervention (PCI), the optimal antithrombotic strategy remains controversial owing to the competing risks of ischemia and bleeding. This study compared the effectiveness and safety of non–vitamin K antagonist oral anticoagulant (NOAC)-based triple antithrombotic therapy (TAT) with those of dual antiplatelet therapy (DAPT) in this population. Methods: Using the Health Insurance Review and Assessment database, we conducted a retrospective cohort study on patients with AF who underwent PCI between 2016 and 2021. Patients receiving NOAC-based TAT or DAPT and were matched 1:1 using propensity scores. The primary endpoint was a composite of ischemic stroke, myocardial infarction, revascularization, and in-hospital death. Secondary outcomes included individual components of the primary endpoint and major bleeding events. Results: After matching, 3,346 patients were included in each group. During a 6-month follow-up, TAT was associated with a significantly lower risk of the composite outcome compared to DAPT (hazard ratio (HR) 0.79, 95% confidence interval (CI) 0.68–0.92; p < 0.01). TAT also reduced the risk of myocardial infarction (HR 0.79, 95% CI 0.62–1.00; p = 0.05), ischemic stroke (HR 0.69, 95% CI 0.48–0.99; p = 0.04), and in-hospital mortality (HR 0.64, 95% CI 0.48–0.87; p < 0.01), with no significant increase in major bleeding (HR 0.91, 95% CI 0.65–1.27; p = 0.59). Conclusion: NOAC-based TAT significantly reduced the risk of composite cardiovascular events without increasing the bleeding risk, supporting its clinical utility in patients with AF undergoing PCI.