Competing Stroke Etiologies and Outcomes After Breakthrough Ischemic Stroke on Oral Anticoagulants in Patients With Atrial Fibrillation

BACKGROUND AND OBJECTIVES: Patients with atrial fibrillation (AF) who experience an ischemic stroke despite oral anticoagulation (OAC) face a high risk of recurrence and bleeding. We aimed to compare 90-day outcomes between patients with and without competing stroke etiologies after a breakthrough ischemic stroke while on OAC for AF. METHODS: ASPERA-R retrospectively enrolled adults (>18 years) with AF who experienced a breakthrough ischemic stroke, defined as either first or recurrent event, occurring on continuous OAC (last intake ≤48 hours), across 35 centers from February 2020 to February 2025. Patients' eligibility required imaging-confirmed ischemic stroke, baseline vessel imaging, and a standardized 90-day follow-up. Patients with inadequate anticoagulant dosing or poor adherence were excluded. Competing etiologies were defined as any additional mechanism coexisting with cardioembolism and plausibly contributing to the index stroke. The primary outcome was 90-day recurrent ischemic stroke; secondary outcomes included modified Rankin Scale shift, myocardial infarction, and vascular and all-cause death. Bleedings were also evaluated. We performed inverse probability weighting to balance baseline covariates and applied Cox or regression models to compare outcomes. RESULTS: = 0.020). Other outcomes did not differ. DISCUSSION: One in 4 patients with AF and breakthrough ischemic stroke on OAC had competing etiologies, most often large artery atherosclerosis. These patients showed higher risk of recurrent stroke, functional dependence, mortality, and bleeding, highlighting the need for development of individualized secondary prevention. Main study limitations include observational retrospective design and incomplete data on on-treatment anticoagulation quality. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT06823466.

Authors

Institutions

Publication Details

Journal
Neurology
Published
2026-04-13
DOI
https://doi.org/10.1212/wnl.0000000000214758
Primary Topic
Atrial Fibrillation Management and Outcomes
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Competing Stroke Etiologies and Outcomes After Breakthrough Ischemic Stroke on Oral Anticoagulants in Patients With Atrial Fibrillation

Valeria Terruso, Leonardo Pantoni, Mauro Silvestrini, Piergiorgio Lochner et al.
Neurology
Atrial Fibrillation Management and Outcomes
article

Competing Stroke Etiologies and Outcomes After Breakthrough Ischemic Stroke on Oral Anticoagulants in Patients With Atrial Fibrillation

Valeria Terruso, Leonardo Pantoni, Mauro Silvestrini, Piergiorgio Lochner, Giuseppe Scopelliti, Ahmed Abdelalim, Maria Rosaria Bagnato, Lucio D’Anna, Francesca Gabriele, Rachele Tortorella, Francesca Bernocchi, Alexandros A. Polymeris, Alberto Fior, L. Zhang, Giovanni Frisullo, P. Candelaresi, Antonio De Mase, Miguel Serôdio, Luisa Vinciguerra, Paola Forti, Andrea Zini, Tamer Roushdy, Maria Guarino, Tara Latimer, Maria Sessa, Petra Črnac Žuna, Marialuisa Zedde, Maria Maddalena Viola, Bernardo Nascimento Antunes, Giovanna Viticchi, Mariarosaria Valente, Pier Andrea Rizzo, Ilaria Cova, Martina Gaia Di Donna, Maria Giulia Mosconi, Mariana A de Souza, Giovanni Merlino, Marina Mannino, Simona Sacco, Hossam Shokri, Lorenzo Barba, Maria Grazia Piscaglia, Angelo Cascio Rizzo, Annalisa Rizzo, Ludovica Migliaccio, Matteo Paolucci, Stefano Forlivesi, Gaurav S. Desai, Matteo Foschi, Ahmed Elbassiouny, Diana Aguiar de Sousa, Raffaele Ornello, Barbara Casolla, Markus Otto, Hrvoje Budinčević, Vincenzo Andreone, Aldobrando Broccolini, Federico De Santis, Nicola Davide Loizzo, Giovanni Di Mauro, Luís Rufo Costa, Marcella Caggiula, Ahmed Nasreldein, Pietro Caliandro, Federico Mazzacane, Vincenzo Laterza, Gabriele Prandin, SOMA BANERJEE, Giuseppe Rinaldi, Ana Catarina Fonseca, Blanca Fuentes, Ahmed Elsayed, Sandeep Buddha, Viktoria Musienko, Carlos Hervás-Testal, Muhammad Elboghdady, Francesco Mele, Ghil Schwarz, Ricardo Rigual, Benjamin Landau, Federica Ferrari, Elena Minguzzi, Roumeisa Khalil, Ana M Barbosa, Marco Vito Rossi, Luca Antonelli, Mona AlBanna, Perla Mazloum, Laura Tudisco, Samah Ali Ismail, Kazi Farhad Ahmed, Sandra Ahmed, Valentina Barone, Giuseppe Reale, Domenico Maisano, Corrado Campisi, Agathe Caraux, Aurelia Zauli, Emanuele Spina, Laura González-Martín
article en

Abstract

BACKGROUND AND OBJECTIVES: Patients with atrial fibrillation (AF) who experience an ischemic stroke despite oral anticoagulation (OAC) face a high risk of recurrence and bleeding. We aimed to compare 90-day outcomes between patients with and without competing stroke etiologies after a breakthrough ischemic stroke while on OAC for AF. METHODS: ASPERA-R retrospectively enrolled adults (>18 years) with AF who experienced a breakthrough ischemic stroke, defined as either first or recurrent event, occurring on continuous OAC (last intake ≤48 hours), across 35 centers from February 2020 to February 2025. Patients' eligibility required imaging-confirmed ischemic stroke, baseline vessel imaging, and a standardized 90-day follow-up. Patients with inadequate anticoagulant dosing or poor adherence were excluded. Competing etiologies were defined as any additional mechanism coexisting with cardioembolism and plausibly contributing to the index stroke. The primary outcome was 90-day recurrent ischemic stroke; secondary outcomes included modified Rankin Scale shift, myocardial infarction, and vascular and all-cause death. Bleedings were also evaluated. We performed inverse probability weighting to balance baseline covariates and applied Cox or regression models to compare outcomes. RESULTS: = 0.020). Other outcomes did not differ. DISCUSSION: One in 4 patients with AF and breakthrough ischemic stroke on OAC had competing etiologies, most often large artery atherosclerosis. These patients showed higher risk of recurrent stroke, functional dependence, mortality, and bleeding, highlighting the need for development of individualized secondary prevention. Main study limitations include observational retrospective design and incomplete data on on-treatment anticoagulation quality. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT06823466.

NeurologyVol. 106(9)
Ain Shams University (EG), Marche Polytechnic University (IT), University of Udine (IT), North Bristol NHS Trust (GB), Beth Israel Deaconess Medical Center (US), University Hospital Centre Zagreb (HR), University of Lisbon (PT), University of Trieste (IT), Cairo University (EG), Imperial College Healthcare NHS Trust (GB), University of Milan (IT), Universidade Politécnica de Viana do Castelo (PT), University of Pavia (IT), University of L'Aquila (IT), King Fahd Medical City (SA), Charing Cross Hospital (GB), University Hospital of Basel (CH), Agostino Gemelli University Polyclinic (IT), Foundation Center (US), Klinička bolnica "Sveti Duh" (HR), Ospedale Antonio Cardarelli (IT), Luigi Sacco Hospital (IT), Psychiatric Hospital Sveti Ivan (HR), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Ospedale degli Infermi (IT), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Unidade Local de Saúde de São José (PT), Hospital de São José (PT), Ospedale Vincenzo Cervello (IT), Military Technical College (EG), Hospital La Paz Institute for Health Research (ES), Urology Foundation (GB), Neuroscience Institute (IT), St George's Hospital (GB), Azienda Ospedaliero-Universitaria Careggi (IT), Ospedale Santa Maria (IT), Casa di Cura Columbus (IT), Azienda USL di Bologna (IT), Istituto delle Scienze Neurologiche di Bologna (IT), Hôpital Pasteur (FR), Azienda Ospedaliera Ospedale Maggiore (IT), Hospital de Santa Maria (PT), University of the Sacred Heart (JP), Ospedale Vito Fazzi (IT), Ospedale Civile di Venezia (IT), Imperial College London (GB), University of Osijek (HR), Universidad Autónoma de Madrid (ES), Misericordia University (US), Martin Luther University Halle-Wittenberg (DE), Assiut University (EG), Saarland University (DE), University of Bologna (IT)
Good health and well-being
Openalex Percentile: Top 25%
Atrial Fibrillation Management and Outcomes
DOISourceOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.