Evidence map›Paper›PMID 42604885›Full record

ArticleJournal of neurology2026

Decoding the causes of ischemic stroke despite ongoing oral anticoagulation and their clinical impact: the ASPERA-R study.

Federico De Santis, Matteo Foschi, Francesca Gabriele, Lucio D'Anna, Andrea Zini, Matteo Paolucci, Stefano Forlivesi, Ludovica Migliaccio, Maria Maddalena Viola, Angelo Cascio Rizzo and 90 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

100 authors.

Federico De SantisDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio Snc, 67100, L'Aquila, Italy.
Matteo FoschiDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio Snc, 67100, L'Aquila, Italy.
Francesca GabrieleDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio Snc, 67100, L'Aquila, Italy.
Lucio D'AnnaDepartment of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS Healthcare Trust, London, UK.
Andrea ZiniDepartment of Neurology and Stroke Center, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Maggiore Hospital, Bologna, Italy.
Matteo PaolucciDepartment of Neurology and Stroke Center, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Maggiore Hospital, Bologna, Italy.
Stefano ForlivesiDepartment of Neurology and Stroke Center, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Maggiore Hospital, Bologna, Italy.
Ludovica MigliaccioDepartment of Neurology and Stroke Center, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Maggiore Hospital, Bologna, Italy.
Maria Maddalena ViolaDepartment of Neurology and Stroke Center, IRCCS Istituto Delle Scienze Neurologiche Di Bologna, Maggiore Hospital, Bologna, Italy.
Angelo Cascio RizzoDepartment of Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Maria SessaDepartment of Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Ghil SchwarzDepartment of Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Rachele TortorellaDepartment of Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
Soma BanerjeeDepartment of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS Healthcare Trust, London, UK.
Gaurav DesaiDepartment of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS Healthcare Trust, London, UK.
Kazi Farhad AhmedDepartment of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS Healthcare Trust, London, UK.
Gabriele PrandinClinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, ASUGI, University of Trieste, Trieste, Italy.
Leonardo PantoniNeuroscience Research Center, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Francesco MeleNeurology Unit, University Hospital Luigi Sacco, Milan, Italy.
Giuseppe ScopellitiNeurology Unit, University Hospital Luigi Sacco, Milan, Italy.
Ilaria CovaNeurology Unit, University Hospital Luigi Sacco, Milan, Italy.
Mariarosaria ValenteClinical Neurology, DMED, University of Udine, Udine, Italy.
Domenico MaisanoClinical Neurology, DMED, University of Udine, Udine, Italy.
Luca AntonelliClinical Neurology, DMED, University of Udine, Udine, Italy.
Maria Rosaria BagnatoUOC Stroke Unit E Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.
Giovanni Di MauroUOC Stroke Unit E Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.
Francesca BernocchiUOC Stroke Unit E Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.
Martina Gaia Di DonnaUOC Stroke Unit E Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.
Barbara CasollaStroke Unit, CHU Pasteur 2, Université Cote d'Azur, UMR2CA URRIS, Nice, France.
Souleymane-M-Bara DialloStroke Unit, CHU Pasteur 2, Université Cote d'Azur, UMR2CA URRIS, Nice, France.
Baptiste AlvarezStroke Unit, CHU Pasteur 2, Université Cote d'Azur, UMR2CA URRIS, Nice, France.
Julie ContentiEmergency Department, Pasteur 2 Hospital, University Hospital Center of Nice, Nice, France.
Laura González-MartìnStroke Center and Department of Neurology, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, Spain.
Ricardo RigualStroke Center and Department of Neurology, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, Spain.
Blanca FuentesStroke Center and Department of Neurology, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, Spain.
Carlos Hervás-TestalStroke Center and Department of Neurology, Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), Madrid, Spain.
Paolo CandelaresiUOC Neurologia E Stroke Unit, AORN Cardarelli, Naples, Italy.
Vincenzo AndreoneUOC Neurologia E Stroke Unit, AORN Cardarelli, Naples, Italy.
Antonio De MaseUOC Neurologia E Stroke Unit, AORN Cardarelli, Naples, Italy.
Emanuele SpinaUOC Neurologia E Stroke Unit, AORN Cardarelli, Naples, Italy.
Diana Aguiar de SousaStroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central - ULS São José, Lisbon, Portugal.
Mariana Almudi SouzaStroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central - ULS São José, Lisbon, Portugal.
Alberto FiorStroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central - ULS São José, Lisbon, Portugal.
Miguel SerôdioStroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central - ULS São José, Lisbon, Portugal.
Pietro CaliandroDepartment of Neuroscience, Catholic University of the Sacred Hearth, Rome, Italy.
Aurelia ZauliDepartment of Neuroscience, Catholic University of the Sacred Hearth, Rome, Italy.
Giuseppe RealeUOC Neuroriabilitazione Ad Alta Intensità, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Ahmed AbdelalimCairo University Stroke Center, Department of Neurology, Faculty of Medicine, Cairo University, Giza, Egypt.
Sandra AhmedCairo University Stroke Center, Department of Neurology, Faculty of Medicine, Cairo University, Giza, Egypt.
Samah Ali IsmailCairo University Stroke Center, Department of Neurology, Faculty of Medicine, Cairo University, Giza, Egypt.
Liqun ZhangDepartment of Neurology, St George's University Hospital, London, UK.
Tara LatimerDepartment of Neurology, St George's University Hospital, London, UK.
Muhammad ElboghdadyDepartment of Neurology, St George's University Hospital, London, UK.
Ahmed ElbassiounyNeurology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Tamer RoushdyNeurology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Hossam ShokriNeurology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Federica FerrariDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Nicola Davide LoizzoDepartment of Emergency Neurology and Stroke Unit, IRCCS Mondino Foundation, Pavia, Italy.
Federico MazzacaneDepartment of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Maria GuarinoIRCCS Istituto Delle Scienze Neurologiche Di Bologna, Bologna, Italy.
Valentina BaroneIRCCS Istituto Delle Scienze Neurologiche Di Bologna, Bologna, Italy.
Paola FortiDepartment of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Giuseppe RinaldiS.C. Neurologia, Ospedale "Di Venere", Bari, Italy.
Marco Vito RossiS.C. Neurologia, Ospedale "Di Venere", Bari, Italy.
Vincenzo LaterzaS.C. Neurologia, Ospedale "Di Venere", Bari, Italy.
Giovanni FrisulloEmergency Neurology - Department of Neuroscience, Sensory Organs, and Thorax - Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy.
Pier Andrea RizzoCatholic University of the Sacred Heart - Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy.
Aldobrando BroccoliniStroke Unit - Department of Neuroscience, Sensory Organs, and Thorax - Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy.
Marina ManninoUOC Neurologia E Stroke Unit, AOOR Villa Sofia-Cervello, Palermo, Italy.
Valeria TerrusoUOC Neurologia E Stroke Unit, AOOR Villa Sofia-Cervello, Palermo, Italy.
Marcella CaggiulaUOC Neurologia E Stroke Unit, PO Vito Fazzi, Lecce, Italy.
Annalisa RizzoUOC Neurologia E Stroke Unit, PO Vito Fazzi, Lecce, Italy.
Ana Catarina FonsecaNeurology Department, Hospital de Santa Maria, Faculdade de Medicina, University of Lisbon, Lisbon, Portugal.
Bernardo AntunesDepartment of Neurology, Hospital de Santa Maria, Lisbon, Portugal.
Ana M BarbosaDepartment of Neurology, Hospital de Santa Maria, Lisbon, Portugal.
Hrvoje BudincevicDepartment of Neurology, Sveti Duh University Hospital, Zagreb, Croatia.
Petra CrnacDepartment of Neurology, Sveti Duh University Hospital, Zagreb, Croatia.
Giovanna ViticchiNeurological Clinic, Marche Polytechnic University, Ancona, Italy.
Mauro SilvestriniNeurological Clinic, Marche Polytechnic University, Ancona, Italy.
Lorenzo BarbaDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Viktoria MusienkoDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Markus OttoDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Piergiorgio LochnerDepartment of Neurology, Saarland University Medical Center, 66421, Homburg, Germany.
Benjamin LandauDepartment of Neurology, Saarland University Medical Center, 66421, Homburg, Germany.
Sandeep BuddhaDepartment of Stroke Medicine, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.
Roumeisa KhalilDepartment of Stroke Medicine, Southmead Hospital, North Bristol NHS Trust, Bristol, UK.
Maria Grazia PiscagliaDepartment of Neurosciences, Stroke Unit - Neurology Unit, S.Maria Delle Croci Hospital, AUSL Romagna, Ravenna, Italy.
Elena MinguzziDepartment of Neurosciences, Stroke Unit - Neurology Unit, S.Maria Delle Croci Hospital, AUSL Romagna, Ravenna, Italy.
Marialuisa ZeddeNeurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS Di Reggio Emilia, Reggio Emilia, Italy.
Ahmed NasreldeinDepartment of Neurology, Assiut University, Assiut, Egypt.
Luisa VinciguerraDepartment of Neurology and Stroke Unit, ASST Crema Hospital, Crema, Italy.
Luis Rufo CostaDepartment of Neurology, Local Health Unit of Alto Minho, Viana Do Castelo, Portugal.
Ahmed Elsaid ElsayedNeurology and Neurointervention Department, Kobry Elkoba Medical Complex, Cairo, Egypt.
Mona AlBannaDepartment of Neurology, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia.
Laura TudiscoStroke Unit, Careggi University Hospital, Florence, Italy.
Maria Giulia MosconiDepartment of Internal and Cardiovascular Medicine, Santa Maria Della Misericordia Hospital, Perugia, Italy.
Alexandros A PolymerisStroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Giovanni MerlinoSOSD Stroke Unit, Udine University Hospital, Udine, Italy.
Simona SaccoDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio Snc, 67100, L'Aquila, Italy.
Raffaele OrnelloDepartment of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio Snc, 67100, L'Aquila, Italy. raffaele.ornello@univaq.it.ORCID http://orcid.org/0000-0001-9501-4031

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOral anticoagulants (OACs), including vitamin K antagonists and direct OACs, reduce stroke risk in atrial fibrillation (AF), yet breakthrough ischemic stroke still occurs in 1-2% of patients annually despite adequate therapy. The mechanisms underlying these events remain unclear. We aimed to identify potential causes of breakthrough ischemic stroke and assess their impact on outcomes, with a focus on drug interactions.

methodsASPERA-R is a multicenter retrospective study including patients with ischemic stroke despite ongoing OAC therapy for AF (February 2020-February 2025). Ongoing treatment was defined by DOAC last intake within 48 h or therapeutic INR levels for VKAs. Potential causes included interacting drugs, active cancer, and competing etiologies. Ninety-day outcomes were compared between patients with and without ≥ 1 potential cause using adjusted Cox regression. Inverse probability-weighted analyses (IPW) evaluated the impact of interacting drugs.

resultsAmong 1649 patients (median age 80.4 years [IQR 73.2-85.6]; 860 [52.2%] female), most were on DOACs (1275; 77.3%), and 724 (43.9%) had ≥ 1 potential cause. Interacting drugs were identified in 28.4%, competing etiologies in 24.3%, and cancer in 4.4% cases. Patients with one or more potential cause had a higher risk of recurrent ischemic stroke at 90 days (HR 2.04, 95% CI 1.18-3.53) compared with those without, with no differences in other outcomes. In the IPW analyses, interacting drugs were associated with increased myocardial infarction risk (HR 3.26, 95% CI 1.30-8.17).

conclusionsPotential causes are identifiable in about half of breakthrough strokes and are associated with higher risk of recurrence compared with those without. Improved detection and management of these factors may reduce recurrence risk, warranting individualized approaches.

Indexed as

AnticoagulantsAtrial FibrillationIschemic StrokeAdministration, OralAgedAged, 80 and overBrain IschemiaDrug InteractionsFemaleHumansMaleNeoplasmsRetrospective StudiesAnticoagulantsAtrial fibrillationBreakthrough ischemic strokeCancerOral anticoagulantsPolypharmacy

Identifiers

PMID42604885
PMCPMC13478031

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.