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Beyond anticoagulation: Statin therapy and 90-day mortality after breakthrough ischemic stroke in atrial fibrillation

G. Merlino R. Ornello L. D'Anna Francesca Gabriele A. Zini M. Paolucci S. Forlivesi L. Migliaccio Maria Maddalena Viola Angelo Cascio Rizzo M. Sessa Ghil Schwarz Rachele Tortorella G. Prandin Soma Banerjee Gurav Desai L. Pantoni F. Mele Giuseppe Scopelliti I. Cova M. Valente Domenico Maisano L. Antonelli Viviana Miele M. R. Bagnato G. Di Mauro Francesca Bernocchi M. D. Di Donna B. Casolla Chiara Bruno Baptiste Alvarez Diallo Souleymane Mbara L. González R. Rigual B. Fuentes C. Hervás P. Candelaresi V. Andreone A. De Mase Emanuele Spina Diana Aguiar de Sousa Mariana Almudi Souza A. Fior Miguel Serôdio P. Caliandro A. Zauli G. Reale A. Abdelalim Sandra M. Ahmed Samah Ali Ismail Li-Qun Zhang Tara Latimer Muhammad Elboghday Ahmed Elbassiouny Tamer M. Roushdy H. Shokri Federica Ferrari N. Loizzo F. Mazzacane M. Guarino Valentina Barone P. Forti G. Rinaldi M. Rossi Vincenzo Laterza G. Frisullo P. Rizzo A. Broccolini M. Mannino V. Terruso M. Caggiula Simona Scalise A. C. Fonseca Bernardo Antunes Hrvoje Budinčević P. Črnac G. Viticchi Mauro Silvestrini M. Otto L. Barba V. Musienko Piergiorgio Lochner Benjamin Landau S. Buddha Roumeisa Khalil M. Piscaglia Elena Minguzzi M. Zedde A. Nasreldein Luisa Vinciguerra L. Costa A. Elsayed Mona AlBanna L. Tudisco M. Mosconi A. Polymeris Federico De Santis S. Sacco Matteo Foschi

Nov 2026 · Therapeutic Advances in Neurological Disorders · 0 citations · 18 references

Abstract

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. 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. Multicenter, retrospective, observational cohort study within the ASPERA-R initiative. 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. 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. 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.

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