Continuation vs Switching Direct Oral Anticoagulant Therapy After Breakthrough Stroke.
| Title: | Continuation vs Switching Direct Oral Anticoagulant Therapy After Breakthrough Stroke. |
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| Authors: | D'Anna L; Department of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS (National Health Service) Healthcare Trust, London, United Kingdom.; Department of Brain Sciences, Imperial College London, London, United Kingdom.; Gabriele F; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.; Ornello R; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.; Zini A; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.; Paolucci M; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.; Forlivesi S; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.; Migliaccio L; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.; Viola MM; Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto delle Scienze Neurologiche di Bologna, Department of Neurology and Stroke Center, Maggiore Hospital, Bologna, Italy.; Rizzo AC; Department of Neurology and Stroke Unit, Azienda Socio Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda, Milan, Italy.; Sessa M; Department of Neurology and Stroke Unit, Azienda Socio Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda, Milan, Italy.; Schwarz G; Department of Neurology and Stroke Unit, Azienda Socio Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda, Milan, Italy.; Tortorella R; Department of Neurology and Stroke Unit, Azienda Socio Sanitaria Territoriale (ASST) Grande Ospedale Metropolitano Niguarda, Milan, Italy.; Prandin G; Clinical Unit of Neurology, Department of Medicine, Surgery and Health Sciences, University Hospital and Health Services of Trieste, Azienda Sanitaria Universitaria Giuliano Isontina, University of Trieste, Trieste, Italy.; Banerjee S; Department of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS (National Health Service) Healthcare Trust, London, United Kingdom.; Desai G; Department of Stroke and Neuroscience, Charing Cross Hospital, Imperial College London NHS (National Health Service) Healthcare Trust, London, United Kingdom.; Pantoni L; Neuroscience Research Center, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.; Department of Neurorehabilitation Sciences, Casa di Cura Igea, Milan, Italy.; Mele F; Neurology Unit, University Hospital Luigi Sacco, Milan, Italy.; Scopelliti G; Neurology Unit, University Hospital Luigi Sacco, Milan, Italy.; Cova I; Neurology Unit, University Hospital Luigi Sacco, Milan, Italy.; Valente M; Clinical Neurology, Department of Medicine, University of Udine, Italy.; Maisano D; Clinical Neurology, Department of Medicine, University of Udine, Italy.; Bagnato MR; L'Unità Operativa Complessa (UOC) Stroke Unit e Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.; Di Mauro G; L'Unità Operativa Complessa (UOC) Stroke Unit e Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.; Bernocchi F; L'Unità Operativa Complessa (UOC) Stroke Unit e Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.; Di Donna MG; L'Unità Operativa Complessa (UOC) Stroke Unit e Neurologia, Ospedale Fabrizio Spaziani, Frosinone, Italy.; Casolla B; Stroke Unit, Centre Hospitalier Universitaire Pasteur 2, Université Cote d'Azur, Unité Mixte de Recherche Clinique Côte d'Azur, Unité de Recherche sur le Syndrome Radiologique Isolé, Nice, France.; Mahagne MH; Stroke Unit, Centre Hospitalier Universitaire Pasteur 2, Université Cote d'Azur, Unité Mixte de Recherche Clinique Côte d'Azur, Unité de Recherche sur le Syndrome Radiologique Isolé, Nice, France.; Amoretti ME; Stroke Unit, Centre Hospitalier Universitaire Pasteur 2, Université Cote d'Azur, Unité Mixte de Recherche Clinique Côte d'Azur, Unité de Recherche sur le Syndrome Radiologique Isolé, Nice, France.; Morgan L; Stroke Unit, Centre Hospitalier Universitaire Pasteur 2, Université Cote d'Azur, Unité Mixte de Recherche Clinique Côte d'Azur, Unité de Recherche sur le Syndrome Radiologique Isolé, Nice, France.; González L; Stroke Center and Department of Neurology, Hospital La Paz Institute for Health Research, La Paz University Hospital-Universidad Autónoma de Madrid, Madrid, Spain.; Rigual R; Stroke Center and Department of Neurology, Hospital La Paz Institute for Health Research, La Paz University Hospital-Universidad Autónoma de Madrid, Madrid, Spain.; Fuentes B; Stroke Center and Department of Neurology, Hospital La Paz Institute for Health Research, La Paz University Hospital-Universidad Autónoma de Madrid, Madrid, Spain.; Hervás C; Stroke Center and Department of Neurology, Hospital La Paz Institute for Health Research, La Paz University Hospital-Universidad Autónoma de Madrid, Madrid, Spain.; Candelaresi P; UOC Neurologia e Stroke Unit, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Napoli, Italy.; Andreone V; UOC Neurologia e Stroke Unit, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Napoli, Italy.; De Mase A; UOC Neurologia e Stroke Unit, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Napoli, Italy.; Spina E; UOC Neurologia e Stroke Unit, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Napoli, Italy.; de Sousa DA; Stroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central-Unidade Local de Saúde (ULS) São José, and Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.; Souza MA; Stroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central-ULS São José, Lisbon, Portugal.; Fior A; Stroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central-ULS São José, Lisbon, Portugal.; Serôdio M; Stroke Center, Department of Neurosciences, Centro Hospitalar Universitário Lisboa Central-ULS São José, Lisbon, Portugal.; Caliandro P; Department of Neuroscience, Catholic University of the Sacred Hearth, Rome, Italy.; UOC Neurology, Department of Neuroscience, Sensory Organs, and Thorax, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Zauli A; Department of Neuroscience, Catholic University of the Sacred Hearth, Rome, Italy.; Reale G; UOC Neuroriabilitazione ad Alta Intensità, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.; Abdelalim A; Cairo University Stroke Center, Department of Neurology, Faculty of Medicine, Cairo University, Cairo, Egypt.; Ahmed S; Cairo University Stroke Center, Department of Neurology, Faculty of Medicine, Cairo University, Cairo, Egypt.; Ismail SA; Cairo University Stroke Center, Department of Neurology, Faculty of Medicine, Cairo University, Cairo, Egypt.; Zhang L; Department of Neurology, St George's University Hospital, London, United Kingdom.; Latimer T; Department of Neurology, St George's University Hospital, London, United Kingdom.; Elboghday M; Department of Neurology, St George's University Hospital, London, United Kingdom.; El Bassiouny A; Neurology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.; Roushdy T; Neurology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.; Shokri H; Neurology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.; Ferrari F; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.; Department of Emergency Neurology and Stroke Unit, IRCCS Mondino Foundation, Pavia, Italy.; Loizzo ND; Department of Emergency Neurology and Stroke Unit, IRCCS Mondino Foundation, Pavia, Italy.; Mazzacane F; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.; Department of Emergency Neurology and Stroke Unit, IRCCS Mondino Foundation, Pavia, Italy.; Guarion M; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.; Barone V; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.; Forti P; Department of Medical and Surgical Sciences, University of Bologna, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.; Rinaldi G; S.C. Neurologia, Ospedale Di Venere, Bari, Italy.; Rossi M; S.C. Neurologia, Ospedale Di Venere, Bari, Italy.; Laterza V; S.C. Neurologia, Ospedale Di Venere, Bari, Italy.; Frisullo G; Emergency Neurology, Department of Neuroscience, Sensory Organs, and Thorax, Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy.; Rizzo PA; Catholic University of the Sacred Heart-Fondazione Policlinico Agostino Gemelli IRCCS, Rome, Italy.; Broccolini A; Stroke Unit, Department of Neuroscience, Sensory Organs, and Thorax, Policlinico Universitario Agostino Gemelli, IRCCS Rome, Rome, Italy.; Mannino M; UOC Neurologia e Stroke Unit, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.; Terruso V; UOC Neurologia e Stroke Unit, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.; Caggiula M; UOC Neurologia e Stroke Unit, Po Vito Fazzi, Lecce, Italy.; Scalise S; UOC Neurologia e Stroke Unit, Po Vito Fazzi, Lecce, Italy.; Fonseca AC; Neurology Department, Hospital de Santa Maria, Faculdade de Medicina, University of Lisbon, Portugal.; Antunes B; Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal.; Budincevic H; Department of Neurology, Sveti Duh University Hospital, Zagreb, Croatia.; Department of Neurology and Neurosurgery, Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.; Department of Psychiatry and Neurology, Faculty of Dental Medicine and Health, J.J. Strossmayer University of Osijek, Osijek, Croatia.; Crnac P; Department of Neurology, Sveti Duh University Hospital, Zagreb, Croatia.; Viticchi G; Neurological Clinic, Marche Polytechnic University, Ancona, Italy.; Silvestrini M; Neurological Clinic, Marche Polytechnic University, Ancona, Italy.; Barba L; Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.; Musienko V; Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle, Germany.; Lochner P; Department of Neurology, Saarland University Medical Center, Homburg, Germany.; Landau B; Department of Neurology, Saarland University Medical Center, Homburg, Germany.; Buddha S; Department of Stroke Medicine, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom.; Khalil R; Department of Stroke Medicine, Southmead Hospital, North Bristol NHS Trust, Bristol, United Kingdom.; Piscaglia MG; Department of Neurosciences, Stroke Unit-Neurology Unit, S. Maria delle Croci Hospital, Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy.; Minguzzi E; Department of Neurosciences, Stroke Unit-Neurology Unit, S. Maria delle Croci Hospital, Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy.; Zedde M; Neurology Unit, Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Italy.; Nasreldein A; Department of Neurology, Assiut University, Assiut, Egypt.; Vinciguerra L; Department of Neurology and Stroke Unit, ASST Crema Hospital, Crema, Italy.; Costa L; Department of Neurology, Local Health Unit of Alto Minho, Viana do Castelo, Portugal.; ElsaidElsayed A; Neurology and Neurointervention Department, Kobry El Koba Medical Complex, Cairo, Egypt.; Al Banna M; Department of Neurology, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia.; Tudisco L; Stroke Unit, Careggi University Hospital, Florence, Italy.; Mosconi MG; Department of Internal and Cardiovascular Medicine, Santa Maria della Misericordia Hospital, Perugia, Italy.; Merlino G; Struttura Operativa Semplice Dipartimentale Stroke Unit, Udine University Hospital, Udine, Italy.; De Santis F; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.; Sacco S; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.; Foschi M; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.; Department of Neurosciences, Stroke Unit-Neurology Unit, S. Maria delle Croci Hospital, Azienda Unità Sanitaria Locale della Romagna, Ravenna, Italy. |
| Source: | JAMA network open [JAMA Netw Open] 2026 Apr 01; Vol. 9 (4), pp. e269584. Date of Electronic Publication: 2026 Apr 01. |
| Publication Type: | Journal Article; Multicenter Study |
| Language: | English |
| Journal Info: | Publisher: American Medical Association Country of Publication: United States NLM ID: 101729235 Publication Model: Electronic Cited Medium: Internet ISSN: 2574-3805 (Electronic) Linking ISSN: 25743805 NLM ISO Abbreviation: JAMA Netw Open Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chicago, IL : American Medical Association, [2018]- |
| MeSH Terms: | Atrial Fibrillation*/drug therapy ; Atrial Fibrillation*/complications ; Anticoagulants*/therapeutic use ; Anticoagulants*/administration & dosage ; Ischemic Stroke*/prevention & control ; Ischemic Stroke*/drug therapy ; Ischemic Stroke*/etiology ; Stroke*/prevention & control ; Stroke*/etiology ; Drug Substitution*/statistics & numerical data; Humans ; Male ; Female ; Aged ; Administration, Oral ; Registries ; Aged, 80 and over ; Middle Aged ; Cohort Studies ; Treatment Outcome |
| Abstract: | Importance: Management after an ischemic stroke occurring despite direct oral anticoagulant (DOAC) therapy for atrial fibrillation (AF) varies widely. Switching anticoagulation is common in clinical practice, although evidence supporting this strategy is limited.; Objective: To evaluate whether continuation of treatment with the same DOAC was noninferior to switching oral anticoagulant therapy with respect to 90-day clinical outcomes.; Design, Setting, and Participants: This multicenter registry-based cohort study with an emulated target trial design included consecutive adult patients with AF who experienced a breakthrough ischemic stroke while receiving uninterrupted DOAC therapy and resumed anticoagulation therapy thereafter. Patients were enrolled between February 2020 and February 2025, across 35 stroke centers in 9 countries in Europe and North Africa, with a standardized 90-day follow-up. The dataset was locked on September 1, 2025. A noninferiority comparison of switching vs continuation strategies was performed. Baseline confounding was addressed using inverse probability of treatment weighting (IPTW). The primary noninferiority margin was an absolute risk difference of 3.0 percentage points in 90-day net clinical benefit.; Exposure: The intervention group switched to treatment with a different DOAC or vitamin K antagonist; the comparator group continued therapy with the prestroke DOAC.; Main Outcomes and Measures: The primary outcome was 90-day net clinical benefit, defined as recurrent ischemic stroke and moderate to severe bleeding. Secondary outcomes included recurrent ischemic events, symptomatic intracerebral hemorrhage, moderate to severe extracranial bleeding, all-cause mortality, and vascular death.; Results: Among 1006 patients included in the analysis (median age, 80.4 [IQR, 73.4-85.4] years; 503 female [50.0%] and 503 [50.0%] male), 463 (46.0%) continued the same DOAC therapy and 543 (54.0%) switched therapy. After IPTW adjustment, the 90-day net clinical benefit was 4.9% with switching and 5.1% with continuation, corresponding to a risk difference of -0.3 percentage points (90% CI, -2.7 to 2.1 percentage points), meeting the prespecified noninferiority criterion. For recurrent ischemic events and bleeding outcomes, the absolute differences were within the predefined noninferiority margins. Noninferiority was not demonstrated for all-cause or vascular mortality.; Conclusions and Relevance: In patients with breakthrough ischemic stroke during DOAC therapy, switching anticoagulation treatment was not associated with clinically meaningful short-term benefit compared with continuation. These findings suggest that switching does not provide additional benefit compared with continuing treatment with the same DOAC. Randomized clinical trials are needed to identify strategies to improve secondary prevention after a breakthrough ischemic stroke. |
| Substance Nomenclature: | 0 (Anticoagulants) |
| Entry Date(s): | Date Created: 20260428 Date Completed: 20260428 Latest Revision: 20260501 |
| Update Code: | 20260501 |
| PubMed Central ID: | PMC13126222 |
| DOI: | 10.1001/jamanetworkopen.2026.9584 |
| PMID: | 42048077 |
| Database: | MEDLINE |
Journal Article; Multicenter Study