{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:28:46Z","timestamp":1793647726723,"version":"4.5.1"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"42","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Acute ischemic stroke (AIS) can occur in patients with non-valvular atrial fibrillation (AF) despite treatment with non-vitamin K antagonist oral anticoagulants (NOACs). This study evaluated clinical, treatment-related, inflammatory, and echocardiographic factors associated with AIS in NOAC-treated patients with AF. This retrospective, 2-center case-control study included 322 patients with non-valvular AF who had received NOAC therapy for at least 3 months. Of these, 112 were hospitalized with AIS and 210 were outpatient controls without AIS at the study assessment. Group differences and factors associated with AIS were evaluated using multivariable logistic regression. ROC analyses were exploratory. Patients with AIS were older than controls and more often had hypertension, diabetes mellitus, coronary artery disease, chronic kidney disease, prior stroke, and prescribed reduced-dose NOAC use. In the adjusted analysis, prior stroke (OR\u2005=\u200532.79), coronary artery disease (OR\u2005=\u20053.47), prescribed reduced-dose NOAC use (OR\u2005=\u20052.55), female sex (OR\u2005=\u20052.26), diabetes mellitus (OR\u2005=\u20051.99), and C-reactive protein (OR per mg\/L\u2005=\u20051.10) were associated with AIS. HAS-BLED (area under the curve\u2005=\u20050.881, 95% CI\u2005=\u20050.844\u20130.918) and CHA\n                      <jats:sub>2<\/jats:sub>\n                      DS\n                      <jats:sub>2<\/jats:sub>\n                      -VASc (area under the curve\u2005=\u20050.840, 95% CI\u2005=\u20050.795\u20130.885) distinguished AIS cases from controls in exploratory ROC analyses. Among NOAC-treated patients with AF, prior stroke and cardiovascular comorbidities were strongly associated with AIS. Prescribed reduced-dose NOAC use was also associated with AIS. Inflammatory markers measured during acute stroke had limited additional value. Because this was a case-control study, the findings do not estimate stroke incidence or future stroke risk and require prospective validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/md.0000000000051189","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:00:47Z","timestamp":1792173647000},"page":"e51189","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Acute ischemic stroke despite NOAC therapy in atrial fibrillation"],"prefix":"10.1097","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-5394","authenticated-orcid":false,"given":"Zeynep","family":"Bastug Gul","sequence":"first","affiliation":[{"name":"Department of Neurology, Health Sciences University, Bakirkoy Prof. Dr. Mazhar Osman Mental Health and Neurological Diseases Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7129-2171","authenticated-orcid":false,"given":"Nasrullah","family":"Danisman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Health Sciences University, Bakirkoy Prof. Dr. Mazhar Osman Mental Health and Neurological Diseases Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1671-8602","authenticated-orcid":false,"given":"Ebru","family":"Ozbezen Kiziltan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Health Sciences University, Bakirkoy Prof. Dr. Mazhar Osman Mental Health and Neurological Diseases Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3539-7090","authenticated-orcid":false,"given":"Gulhan","family":"Yildirim Ozdemir","sequence":"additional","affiliation":[{"name":"Department of Neurology, Health Sciences University, Bakirkoy Prof. Dr. Mazhar Osman Mental Health and Neurological Diseases Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1686-6437","authenticated-orcid":false,"given":"Vasfiye","family":"Kabeloglu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Health Sciences University, Bakirkoy Prof. Dr. Mazhar Osman Mental Health and Neurological Diseases Training and Research Hospital, Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4456-6818","authenticated-orcid":false,"given":"Serkan","family":"Yazan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Health Sciences University, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-1427","authenticated-orcid":false,"given":"Mehmet","family":"Gul","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Health Sciences University, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20261102","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1161\/01.STR.22.8.983","article-title":"Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.","volume":"22","author":"Wolf","year":"1991","journal-title":"Stroke"},{"key":"R2-20261102","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1161\/01.STR.0000166053.83476.4a","article-title":"Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study.","volume":"36","author":"Marini","year":"2005","journal-title":"Stroke"},{"key":"R3-20261102","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/S0140-6736(13)62343-0","article-title":"Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.","volume":"383","author":"Ruff","year":"2014","journal-title":"Lancet"},{"key":"R4-20261102","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1093\/eurheartj\/ehae176","article-title":"2024 ESC guidelines for the management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).","volume":"45","author":"Van Gelder","year":"2024","journal-title":"Eur Heart J"},{"key":"R5-20261102","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1378\/chest.09-1584","article-title":"Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on atrial fibrillation.","volume":"137","author":"Lip","year":"2010","journal-title":"Chest"},{"key":"R6-20261102","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1378\/chest.10-0134","article-title":"A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.","volume":"138","author":"Pisters","year":"2010","journal-title":"Chest"},{"key":"R7-20261102","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/CIR.0000000000001193","article-title":"2023 ACC\/AHA\/ACCP\/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology\/American Heart Association Joint Committee on clinical practice guidelines.","volume":"149","author":"Joglar","year":"2024","journal-title":"Circulation"},{"key":"R8-20261102","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1016\/j.jacc.2017.03.600","article-title":"Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction.","volume":"69","author":"Yao","year":"2017","journal-title":"J Am Coll Cardiol"},{"key":"R9-20261102","doi-asserted-by":"crossref","first-page":"2597","DOI":"10.1016\/j.jacc.2016.09.966","article-title":"Off-label dosing of non-vitamin K antagonist oral anticoagulants and adverse outcomes: the ORBIT-AF II registry.","volume":"68","author":"Steinberg","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"R10-20261102","doi-asserted-by":"crossref","first-page":"j510","DOI":"10.1136\/bmj.j510","article-title":"Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.","volume":"356","author":"Nielsen","year":"2017","journal-title":"BMJ"},{"key":"R11-20261102","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1161\/STROKEAHA.119.025350","article-title":"Causes and risk factors of cerebral ischemic events in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants for stroke prevention.","volume":"50","author":"Paciaroni","year":"2019","journal-title":"Stroke"},{"key":"R12-20261102","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/ana.25700","article-title":"Ischemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation.","volume":"87","author":"Seiffge","year":"2020","journal-title":"Ann Neurol"},{"key":"R13-20261102","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1136\/jnnp-2021-328391","article-title":"Aetiology, secondary prevention strategies and outcomes of ischaemic stroke despite oral anticoagulant therapy in patients with atrial fibrillation.","volume":"93","author":"Polymeris","year":"2022","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"R14-20261102","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/ana.25917","article-title":"Prior anticoagulation in patients with ischemic stroke and atrial fibrillation.","volume":"89","author":"Meinel","year":"2021","journal-title":"Ann Neurol"},{"key":"R15-20261102","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1161\/STROKEAHA.121.038239","article-title":"Recurrent ischemic stroke and bleeding in patients with atrial fibrillation who suffered an acute stroke while on treatment with nonvitamin K antagonist oral anticoagulants: the RENO-EXTEND study.","volume":"53","author":"Paciaroni","year":"2022","journal-title":"Stroke"},{"key":"R16-20261102","doi-asserted-by":"crossref","first-page":"e034758","DOI":"10.1161\/JAHA.123.034758","article-title":"Residual stroke risk among patients with atrial fibrillation prescribed oral anticoagulants: a patient-level meta-analysis from COMBINE AF.","volume":"13","author":"Johnson","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"R17-20261102","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1093\/europace\/euab065","article-title":"2021 European Heart Rhythm Association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.","volume":"23","author":"Steffel","year":"2021","journal-title":"Europace"},{"key":"R18-20261102","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1161\/01.STR.32.4.917","article-title":"C-reactive protein in ischemic stroke: an independent prognostic factor.","volume":"32","author":"Di Napoli","year":"2001","journal-title":"Stroke"},{"key":"R19-20261102","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1161\/STROKEAHA.110.594945","article-title":"Inflammatory mechanisms of 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tips.","volume":"32","author":"Anwar","year":"2024","journal-title":"J Cardiovasc Imaging"},{"key":"R23-20261102","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.echo.2025.07.009","article-title":"Multimodality imaging in evaluating and guiding percutaneous left atrial appendage occlusion.","volume":"38","author":"Jain","year":"2025","journal-title":"J Am Soc Echocardiogr"},{"key":"R24-20261102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.echo.2014.10.003","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.","volume":"28","author":"Lang","year":"2015","journal-title":"J Am Soc Echocardiogr"}],"container-title":["Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1097\/MD.0000000000051189","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:00:53Z","timestamp":1793646053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1097\/MD.0000000000051189"}},"subtitle":["Clinical factors associated with AIS in a 2-center observational case-control study"],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":24,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/md.0000000000051189","relation":{},"ISSN":["0025-7974","1536-5964"],"issn-type":[{"value":"0025-7974","type":"print"},{"value":"1536-5964","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"2026-06-10","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-02","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}