Does add-on antiplatelet therapy reduce ischemic events or increase bleeding in anticoagulated patients with non-valvular atrial fibrillation?
Non-valvular atrial fibrillation (AF) patients treated with anticoagulation, excluding those within 1 year after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)
Add-on antiplatelet therapy (aspirin, P2Y12 inhibitors, and/or cilostazol) plus oral anticoagulants (OAC + APT)
Oral anticoagulants alone (OAC alone)
Primary ischemic endpoint (composite of all-cause death, ischemic stroke, systemic embolism, and myocardial infarction) and primary bleeding endpoint (any bleeding, composite of major bleeding and clinically relevant non-major bleeding)composite
Adding antiplatelet therapy to oral anticoagulation in patients with atrial fibrillation (without recent PCI/CABG) is associated with increased risks of both ischemic and bleeding events.
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. 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. 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). 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.
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Yuki Matsuoka
Hitoshi Minamiguchi
Daisuke Sakamoto
IJC Heart & Vasculature
The University of Osaka
Nihon University
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Matsuoka et al. (Fri,) studied this question.
www.synapsesocial.com/papers/69c0df0bfddb9876e79c159e — DOI: https://doi.org/10.1016/j.ijcha.2026.101907
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