Matteo Foschi, Lucio D’Anna, Francesca Gabriele, Raffaele Ornello, Andrea Zini, Matteo Paolucci, Stefano Forlivesi, Ludovica Migliaccio, Maria Maddalena Viola, Angelo Cascio Rizzo, Maria Sessa, Ghil Schwarz, Rachele Tortorella, SOMA BANERJEE, Gaurav S. Desai, Muhammad Jaffar, 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, Perla Mazloum, Chiara Bruno, Baptiste Alvarez, Laura Gonzalez‐Martin, Ricardo Rigual, Blanca Fuentes, Carlos Hervás, P Candelaresi, V. Andreone, Antonio De Mase, Emanuele Spina, Diana Aguiar de Sousa, Mariana A de Souza, Alberto Fior, Miguel Serôdio, P. Caliandro, Aurelia Zauli, Giuseppe Reale, Ahmed Abdelalim, Sandra Ahmed, Nourhan Mohamed Soliman, Liqun Zhang, Tara Latimer, Muhammad Elboghday, Ahmed Aly 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, Guglielmo Lucchese, Ana Catarina Fonseca, Bernardo Nascimento 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, L. C. Costa, Ahmed Elsayed, Mona AlBanna, Laura Tudisco, Maria Giulia Mosconi, Giovanni Merlino, Alexandros Polymeris, Federico De Santis, Simona Sacco
Background Sex‐specific outcomes after breakthrough ischemic stroke on oral anticoagulation (OAC) are unexplored. We compared 90‐day outcomes by sex and explored modifiers. Methods ASPERA‐R (Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants retrospective cohort; NCT06823466) was an international, multicenter, retrospective study enrolling adults (aged >18 years) with breakthrough ischemic stroke on OAC for atrial fibrillation. Primary outcome was 90‐day return to baseline neurologic function (modified Rankin Scale [mRS] score 0–1 maintained if prestroke 0–1; or same/lower mRS score if prestroke ≥2). Secondary outcomes were 90‐day mRS shift, recurrent ischemic stroke/transient ischemic attack, myocardial infarction, and all‐cause and vascular death. Safety outcomes included 90‐day moderate‐to‐severe bleeding, intracranial hemorrhage, 24‐hour hemorrhagic transformation, and 24‐hour symptomatic intracranial hemorrhage. We applied inverse probability weighting and regression models to compare outcomes. Prespecified subgroup analysis tested sex‐specific interactions. Results We included 1649 patients (women, 52.2%; mean±SD age, 78.0±10.7 years). Women were older (80.2±9.6 versus 76.3±10.8 years; unweighted standardized mean difference=0.376), had higher baseline National Institutes of Health Stroke Scale score (13 [interquartile range, 9–19] versus 9 [interquartile range, 4–17]; unweighted standardized mean difference=0.227), and worse prestroke mRS score (unweighted standardized mean difference=0.237). After weighting, women were less likely to return to baseline neurologic function (35.2% versus 42.7%; adjusted risk ratio, 0.82 [95% CI, 0.71–0.96]; P =0.015), had worse mRS distribution (adjusted odds ratio, 1.17 [95% CI, 1.01–1.37]; P =0.043), and had higher recurrent ischemic stroke/transient ischemic attack (4.8% versus 2.8%; adjusted hazard ratio [HR], 1.70 [95% CI, 1.01–2.86]; P =0.045). Women showed a trend toward more moderate‐to‐severe bleeding (4.6% versus 2.8%; adjusted HR, 1.63 [95% CI, 0.96–2.72]; P =0.070). Subgroup analyses revealed significant sex interactions for OAC type, competing cause, endovascular treatment, and OAC restart. Conclusions Women had worse 90‐day outcomes than men after breakthrough ischemic stroke on OAC for atrial fibrillation, highlighting the need for sex‐aware management.