Add-on antiplatelet therapy in anticoagulated patients with atrial fibrillation.

Background: The impact of add-on antiplatelet therapy in patients with atrial fibrillation (AF) on oral anticoagulants (OAC) in real-world clinical practice remains to be investigated. Methods: We conducted DIRECT-Extend registry, a pooled analysis combining three large-scale real-world datasets of non-valvular AF patients treated with anticoagulation. We assessed clinical impacts of the add-on antiplatelet therapy using the inverse-probability-of-treatment weighting methods. Antiplatelet therapy included aspirin, P2Y12 inhibitors, and cilostazol (dual therapy included). The primary ischemic endpoint was a composite of all-cause death, ischemic stroke, systemic embolism, and myocardial infarction. The primary bleeding endpoint was any bleeding, defined as a composite of major bleeding and clinically relevant non-major bleeding according to the criteria of the International Society on Thrombosis and Hemostasis. Results: A total 7387 eligible patients (excluding those within 1 year after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)) were divided into two groups: the OAC alone group (N = 6096) and the OAC + APT group (treated with both OAC and antiplatelet therapy, N = 1291). The median follow-up period was 1012 [404, 1344] days. The risk for both the primary ischemic and bleeding endpoint was higher in patients in OAC + APT group than those in OAC alone group (ischemic endpoint, weighted hazard ratio (wHR): 1.28, 95%CI [1.17 - 1.40], p < 0.001; bleeding endpoint, wHR: 1.26 [1.19-1.33], p < 0.001). Conclusion: The large-scale real-world data demonstrated that, in AF patients treated with OAC, add-on antiplatelet therapy was associated with a higher risk for both ischemic and bleeding endpoints. These findings may not be generalizable to the early post-PCI/CABG period.