Authors
Federico De Santis, Matteo Foschi, Francesca Gabriele, Lucio D'Anna, Andrea Zini, Matteo Paolucci, Stefano Forlivesi, Ludovica Migliaccio, Maria Maddalena Viola, Angelo Cascio Rizzo, Maria Sessa, Ghil Schwarz, Rachele Tortorella, Soma Banerjee, Gaurav Desai, Kazi Farhad Ahmed, Gabriele Prandin, Leonardo Pantoni, Francesco Mele, Giuseppe Scopelliti, Ilaria Cova, Mariarosaria Valente, Domenico Maisano, Luca Antonelli, Maria Rosaria Bagnato, Giovanni Di Mauro, Francesca Bernocchi, Martina Gaia Di Donna, Barbara Casolla, Souleymane-M-Bara Diallo, Baptiste Alvarez, Julie Contenti, Laura González-Martìn, Ricardo Rigual, Blanca Fuentes, Carlos Hervás-Testal, Paolo Candelaresi, Vincenzo Andreone, Antonio De Mase, Emanuele Spina, Diana Aguiar de Sousa, Mariana Almudi Souza, Alberto Fior, Miguel Serôdio, Pietro Caliandro, Aurelia Zauli, Giuseppe Reale, Ahmed Abdelalim, Sandra Ahmed, Samah Ali Ismail, Liqun Zhang, Tara Latimer, Muhammad Elboghdady, Ahmed Elbassiouny, Tamer Roushdy, Hossam Shokri, Federica Ferrari, Nicola Davide Loizzo, Federico Mazzacane, Maria Guarino, Valentina Barone, Paola Forti, Giuseppe Rinaldi, Marco Vito Rossi, Vincenzo Laterza, Giovanni Frisullo, Pier Andrea Rizzo, Aldobrando Broccolini, Marina Mannino, Valeria Terruso, Marcella Caggiula, Annalisa Rizzo, Ana Catarina Fonseca, Bernardo Antunes, Ana M Barbosa, Hrvoje Budincevic, Petra Crnac, Giovanna Viticchi, Mauro Silvestrini, Lorenzo Barba, Viktoria Musienko, Markus Otto, Piergiorgio Lochner, Benjamin Landau, Sandeep Buddha, Roumeisa Khalil, Maria Grazia Piscaglia, Elena Minguzzi, Marialuisa Zedde, Ahmed Nasreldein, Luisa Vinciguerra, Luis Rufo Costa, Ahmed Elsaid Elsayed, Mona AlBanna, Laura Tudisco, Maria Giulia Mosconi, Alexandros A Polymeris, Giovanni Merlino, Simona Sacco, Raffaele Ornello
Published in
Journal of neurology. Volume 273. Issue 9. Aug 17, 2026. Epub Aug 17, 2026.
Abstract
Oral anticoagulants (OACs), including vitamin K antagonists and direct OACs, reduce stroke risk in atrial fibrillation (AF), yet breakthrough ischemic stroke still occurs in 1-2% of patients annually despite adequate therapy. The mechanisms underlying these events remain unclear. We aimed to identify potential causes of breakthrough ischemic stroke and assess their impact on outcomes, with a focus on drug interactions.
ASPERA-R is a multicenter retrospective study including patients with ischemic stroke despite ongoing OAC therapy for AF (February 2020-February 2025). Ongoing treatment was defined by DOAC last intake within 48 h or therapeutic INR levels for VKAs. Potential causes included interacting drugs, active cancer, and competing etiologies. Ninety-day outcomes were compared between patients with and without ≥ 1 potential cause using adjusted Cox regression. Inverse probability-weighted analyses (IPW) evaluated the impact of interacting drugs.
Among 1649 patients (median age 80.4 years [IQR 73.2-85.6]; 860 [52.2%] female), most were on DOACs (1275; 77.3%), and 724 (43.9%) had ≥ 1 potential cause. Interacting drugs were identified in 28.4%, competing etiologies in 24.3%, and cancer in 4.4% cases. Patients with one or more potential cause had a higher risk of recurrent ischemic stroke at 90 days (HR 2.04, 95% CI 1.18-3.53) compared with those without, with no differences in other outcomes. In the IPW analyses, interacting drugs were associated with increased myocardial infarction risk (HR 3.26, 95% CI 1.30-8.17).
Potential causes are identifiable in about half of breakthrough strokes and are associated with higher risk of recurrence compared with those without. Improved detection and management of these factors may reduce recurrence risk, warranting individualized approaches.
PMID:
42604885
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.
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