Beyond anticoagulation: Statin therapy and 90-day mortality after breakthrough ischemic stroke in atrial fibrillation
Giovanni Merlino, Raffaele Ornello, Lucio D’Anna, Francesca Gabriele, Andrea Zini, Matteo Paolucci, Stefano Forlivesi, Ludovica Migliaccio, Maria Maddalena Viola, Angelo Cascio Rizzo, Maria Sessa, Ghil Schwarz, Rachele Tortorella, Gabriele Prandin, Soma Banerjee, Gurav Desai, Leonardo Pantoni, Francesco Mele, Giuseppe Scopelliti, Ilaria Cova, Mariarosaria Valente, Domenico Maisano, Luca Antonelli, Viviana Miele, Maria Rosaria Bagnato, Giovanni Di Mauro, Francesca Bernocchi, Martina Gaia Di Donna, Barbara Casolla, Chiara Bruno, Baptiste Alvarez, Diallo Souleymane-M-Bara, Laura González, Ricardo Rigual, Blanca Fuentes, Carlos Hervás, 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 Elboghday, Ahmed El Bassiouny, Tamer Roushdy, Hossam Shokri, Federica Ferrari, Nicola Davide Loizzo, Federico Mazzacane, Maria Guarino, Valentina Barone, Paola Forti, Giuseppe Rinaldi, Marco Rossi, Vincenzo Laterza, Giovanni Frisullo, Pier Andrea Rizzo, Aldobrando Broccolini, Marina Mannino, Valeria Terruso, Marcella Caggiula, Simona Scalise, Ana Catarina Fonseca, Bernardo Antunes, Hrvoje Budincevic, Petra Crnac, Giovanna Viticchi, Mauro Silvestrini, Markus Otto, Lorenzo Barba, Viktoria Musienko, Piergiorgio Lochner, Benjamin Landau, Sandeep Buddha, Roumeisa Khalil, Maria Grazia Piscaglia, Elena Minguzzi, Marialuisa Zedde, Ahmed Nasreldein, Luisa Vinciguerra, Luis Costa, Ahmed Elsayed, Mona Al Banna, Laura Tudisco, Maria Giulia Mosconi, Alexandros A. Polymeris, Federico De Santis, Simona Sacco, Matteo FoschiBackground
Secondary stroke prevention in patients with atrial fibrillation (AF) who experience an ischemic stroke (IS) despite oral anticoagulation remains challenging, and strategies have focused on antithrombotic optimization or left atrial appendage occlusion. Adjunctive statin therapy might reduce early vascular risk and mortality in this high-risk population.
Objectives
To evaluate the association between statin therapy at hospital discharge and 90-day all-cause death (primary outcome) in patients with AF experiencing IS despite oral anticoagulation.
Design
Multicenter, retrospective, observational cohort study within the ASPERA-R initiative.
Methods
Consecutive adults admitted between February 2020 and February 2025 with IS occurring during continuous oral anticoagulation for AF were included. Time-to-event analyses were landmarked at discharge to minimize immortal-time bias. Secondary outcomes were a composite vascular outcome (recurrent IS, transient ischemic attack (TIA), or vascular death) and recurrent IS/TIA; moderate-to-severe bleeding and intracranial hemorrhage (ICH) were assessed for safety. Inverse probability weighting (IPW) on a prespecified propensity score addressed confounding by indication, and weighted Cox models were fitted, with sensitivity analyses for the primary outcome.
Results
Among 1,442 patients discharged alive, 1,016 (70.5%) received statins at discharge. After weighting, propensity-score covariates were balanced. Over 90 days, statin therapy was associated with lower all-cause mortality (9.6% vs. 19.2%; HR 0.55, 95% CI 0.39-0.79). The composite vascular outcome showed a directionally similar but borderline association (HR 0.63, 95% CI 0.40-1.00); recurrent IS/TIA was not associated. Moderate-to-severe bleeding and ICH were rare and did not differ between groups. The mortality association was consistent across sensitivity analyses.
Conclusion
In AF patients with IS despite oral anticoagulation, statin therapy at discharge was associated with lower 90-day all-cause mortality, without increased short-term bleeding. Given the observational design, these hypothesis-generating findings support prospective evaluation of statins in this population.