Impact of Inflammatory Burden on Outcomes After Breakthrough Ischemic Stroke: Insights From the ASPERA-R Study

BACKGROUND: Patients with atrial fibrillation who experience ischemic stroke despite oral anticoagulation (breakthrough stroke) remain at high risk of recurrent vascular events and death. Although inflammation has been associated with thromboembolic risk, its prognostic role in breakthrough stroke remains unclear. We investigated whether a composite inflammatory burden index was associated with adverse outcomes after breakthrough ischemic stroke. METHODS: scores, and combined into a composite inflammatory burden index. Patients were classified as having high (upper tertile) or lower inflammatory burden (lower 2 tertiles). Outcomes included new 90-day ischemic events (recurrent ischemic stroke, transient ischemic attack, or systemic embolism), 24-hour hemorrhagic transformation, and 90-day moderate-to-severe bleeding, intracranial hemorrhage, and mortality. Inverse probability of treatment weighting accounted for center, demographics, vascular risk factors and comorbidities, anticoagulation, competing stroke causes, baseline National Institutes of Health Stroke Scale, prestroke modified Rankin Scale, and time to blood collection. RESULTS: Among 1649 patients enrolled in ASPERA-R, 671 patients from 14 centers had complete biomarker data (median age, 80.1 years [interquartile range, 73.5-85.5]; 52.3% female). Of these, 223 (33.2%) had high inflammatory burden, and 448 (66.8%) had lower inflammatory burden. After weighting, high inflammatory burden was associated with increased risks of ischemic events at 90 days (hazard ratio, 1.53 [95% CI, 1.02-2.30]), all-cause mortality (hazard ratio, 1.70 [95% CI, 1.17-2.47]), moderate-to-severe bleeding (hazard ratio, 2.92 [95% CI, 1.04-8.17]), and hemorrhagic transformation at 24 hours (odds ratio, 2.18 [95% CI, 1.43-3.33]). CONCLUSIONS: In breakthrough ischemic stroke, high inflammatory burden was associated with increased risks of recurrent ischemic events, mortality, hemorrhagic transformation, and major bleeding. A composite of routinely available inflammatory biomarkers may help identify patients with higher residual vascular risk.

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Journal
Stroke
Published
2026-10-29
DOI
https://doi.org/10.1161/strokeaha.126.057542
Primary Topic
Acute Ischemic Stroke Management
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article
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article

Impact of Inflammatory Burden on Outcomes After Breakthrough Ischemic Stroke: Insights From the ASPERA-R Study

Leonardo Pantoni, Giuseppe Scopelliti, Ahmed Abdelalim, Lucio D’Anna et al.
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Stroke
Acute Ischemic Stroke Management
article

Impact of Inflammatory Burden on Outcomes After Breakthrough Ischemic Stroke: Insights From the ASPERA-R Study

Leonardo Pantoni, Giuseppe Scopelliti, Ahmed Abdelalim, Lucio D’Anna, Francesca Gabriele, Rachele Tortorella, Alexandros A. Polymeris, Liqun Zhang, Ghil Schwarz, Sandra Mohamed Ahmed, Tara Latimer, Maria Sessa, Blanca Fuentes, Marialuisa Zedde, Francesco Mele, Aurelia Zauli, Marjolaine Baude, Ilaria Cova, Soma Banerjee, Federica Ferrari, Simona Sacco, Maria Grazia Piscaglia, Angelo Cascio Rizzo, Giuseppe Reale, Ana Catarina Fonseca, Matteo Foschi, Raffaele Ornello, Barbara Casolla, Federico De Santis, Bernardo Antunes, Ricardo Rigual, Pietro Caliandro, Federico Mazzacane, Gabriele Prandin, Ahmed Elsaid Elsayed, Laura Gonzalez, Muhammad Jaffar, Muhammad Elboghday, Samah Ali Ismail, Gurav Desai, Ludovica Maria Miserocchi, Giorgia Balducci, Souleymane-M.-Bara Diallo, Monica Gulla
article en

Abstract

BACKGROUND: Patients with atrial fibrillation who experience ischemic stroke despite oral anticoagulation (breakthrough stroke) remain at high risk of recurrent vascular events and death. Although inflammation has been associated with thromboembolic risk, its prognostic role in breakthrough stroke remains unclear. We investigated whether a composite inflammatory burden index was associated with adverse outcomes after breakthrough ischemic stroke. METHODS: scores, and combined into a composite inflammatory burden index. Patients were classified as having high (upper tertile) or lower inflammatory burden (lower 2 tertiles). Outcomes included new 90-day ischemic events (recurrent ischemic stroke, transient ischemic attack, or systemic embolism), 24-hour hemorrhagic transformation, and 90-day moderate-to-severe bleeding, intracranial hemorrhage, and mortality. Inverse probability of treatment weighting accounted for center, demographics, vascular risk factors and comorbidities, anticoagulation, competing stroke causes, baseline National Institutes of Health Stroke Scale, prestroke modified Rankin Scale, and time to blood collection. RESULTS: Among 1649 patients enrolled in ASPERA-R, 671 patients from 14 centers had complete biomarker data (median age, 80.1 years [interquartile range, 73.5-85.5]; 52.3% female). Of these, 223 (33.2%) had high inflammatory burden, and 448 (66.8%) had lower inflammatory burden. After weighting, high inflammatory burden was associated with increased risks of ischemic events at 90 days (hazard ratio, 1.53 [95% CI, 1.02-2.30]), all-cause mortality (hazard ratio, 1.70 [95% CI, 1.17-2.47]), moderate-to-severe bleeding (hazard ratio, 2.92 [95% CI, 1.04-8.17]), and hemorrhagic transformation at 24 hours (odds ratio, 2.18 [95% CI, 1.43-3.33]). CONCLUSIONS: In breakthrough ischemic stroke, high inflammatory burden was associated with increased risks of recurrent ischemic events, mortality, hemorrhagic transformation, and major bleeding. A composite of routinely available inflammatory biomarkers may help identify patients with higher residual vascular risk.

Stroke
Università Cattolica del Sacro Cuore (IT), Centre National de la Recherche Scientifique (FR), St George's Hospital (GB), University of Lisbon (PT), University of Trieste (IT), Cairo University (EG), Imperial College Healthcare NHS Trust (GB), St George's, University of London (GB), University of Basel (CH), University of Milan (IT), Université Paris-Est Créteil (FR), Université Côte d'Azur (FR), University of Pavia (IT), University of L'Aquila (IT), Paris-Est Sup (FR), Hospital Universitario La Paz (ES), Charing Cross Hospital (GB), University Hospital of Basel (CH), Agostino Gemelli University Polyclinic (IT), Luigi Sacco Hospital (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Laboratoire de PhysioMédecine Moléculaire (FR), Ospedale "Santa Maria delle Croci" di Ravenna (IT), Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT), Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IT), Hôpital l'Archet (FR), Hôpital Pasteur (FR), Hospital de Santa Maria (PT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Imperial College London (GB), Universidad Autónoma de Madrid (ES)
Good health and well-being
Openalex Percentile: Top 12%
Acute Ischemic Stroke Management
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