{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:43:36Z","timestamp":1789037016301,"version":"build-2803163510"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Intravenous thrombolysis (IVT) in patients with recent ingestion of direct oral anticoagulants (DOACs) is a frequent challenge and remains controversial. The benefit of DOAC reversal before IVT is uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Using target trial methodology, we analyzed data from 28 comprehensive stroke centers. Patients on DOACs were included if they met IVT criteria, had a National Institutes of Health Stroke Scale score of \u22652, and last DOAC intake within 48 hours or was undeterminable. Safety and efficacy outcomes (symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, major bleeding, 90-day mortality, and good functional outcome [modified Rankin Scale score of 0\u20132 or return to baseline]) were compared between those receiving IVT versus no IVT and IVT with versus without reversal. In addition, a comparison was made with patients from the New Zealand stroke registry, all of whom underwent reversal with idarucizumab. We adjusted for covariates known to be associated with safety and efficacy outcomes, including age, stroke severity, intended thrombectomy, blood glucose, blood pressure, DOAC reversal, and time from last intake.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Overall, 1342 patients fulfilled the target trial criteria. The median age was 80 (interquartile range, 73\u201386) years, median National Institutes of Health Stroke Scale score was 11, 50% were female, and 52% of patients received endovascular therapy. IVT was given in 342 of 1342 (25%) patients. Of these, 141 (41.2%) had verified DOAC intake &lt;12 hours before admission, and 92 (26.9%) within 12 to 24 hours. Symptomatic intracerebral hemorrhage occurred in 10 of 328 (3.0%) of patients receiving IVT and 54 of 921 (5.9%) patients not receiving IVT (adjusted difference, \u22122.1% [95% CI, \u22125.3% to +1.2]). Patients receiving IVT were more likely to have good functional outcomes (adjusted difference, +14.4% [95% CI, +7.1% to +21.8%]). Comparing 289 patients with reversal (from the additional New Zealand registry) and 283 patients without reversal before IVT (from the target trial population), there was no significant difference in symptomatic intracerebral hemorrhage, major bleeding, or efficacy outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This target trial confirms previous observational data regarding the safety of off-label IVT in patients with recent DOAC intake. More data and dedicated trials are needed for patients with confirmed high DOAC plasma levels and regarding the efficacy and safety of DOAC reversal before IVT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.051384","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T09:00:28Z","timestamp":1753174828000},"page":"2836-2845","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Intravenous Thrombolysis in Patients With Recent Intake of Direct Oral Anticoagulants: A Target Trial Analysis and Comparison With Reversal Agent Use"],"prefix":"10.1161","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0647-9273","authenticated-orcid":true,"given":"Thomas R.","family":"Meinel","sequence":"first","affiliation":[{"name":"Department of Neurology, Stroke Research Center Bern (T.R.M., P.B., F.Z.-M., U.F., D.J.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5204-2016","authenticated-orcid":true,"given":"Philipp","family":"B\u00fccke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Stroke Research Center Bern (T.R.M., P.B., F.Z.-M., U.F., D.J.S.), Inselspital, Bern University Hospital, University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4349-3322","authenticated-orcid":true,"given":"Lucio","family":"D\u2019Anna","sequence":"additional","affiliation":[{"name":"Division of Brain Sciences, Imperial College London, United Kingdom (L.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6525-9529","authenticated-orcid":true,"given":"Giovanni","family":"Merlino","sequence":"additional","affiliation":[{"name":"Clinical Neurology and Stroke Unit, Department of Head, Neck and Neurosciences, Udine University Hospital, Italy (G.M., A.B., L.C., M.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-7924","authenticated-orcid":true,"given":"Diana","family":"Aguiar de Sousa","sequence":"additional","affiliation":[{"name":"Stroke Centre, Lisbon Central University Hospital Center\u2013ULS S\u00e3o Jos\u00e9, Portugal (D.A.d.S., M.E.M., C.G.)."},{"name":"CEEM e Instituto de Anatomia, Faculdade de Medicina, Universidade de Lisboa, Portugal (D.A.d.S., M.E.M., C.G.)."},{"name":"Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal (D.A.d.S., M.E.M., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0286-8781","authenticated-orcid":true,"given":"Sven","family":"Poli","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke (S.P., A.G.-E.), University of T\u00fcbingen, Germany."},{"name":"Hertie Institute for Clinical Brain Research (S.P., A.G.-E.), University of T\u00fcbingen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-4972","authenticated-orcid":true,"given":"Jan C.","family":"Purrucker","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heidelberg University Hospital, Germany (J.C.P., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4429-2714","authenticated-orcid":true,"given":"Davide","family":"Strambo","sequence":"additional","affiliation":[{"name":"Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland (D.S., G.T., P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-8543","authenticated-orcid":true,"given":"Michele","family":"Romoli","sequence":"additional","affiliation":[{"name":"Neurology and Stroke Unit, Department of Neurosciences, Bufalini Hospital, AUSL Romagna, Cesena, Italy (M.R., G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-9780","authenticated-orcid":true,"given":"Gian Marco","family":"De Marchis","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, University Research and Teaching Hospital, Cantonal Hospital St. Gallen, Switzerland (G.M.D.M., D.V.)."},{"name":"Medical Faculty, University of Basel, Switzerland (G.M.D.M., D.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6935-8842","authenticated-orcid":true,"given":"Waltraud","family":"Pfeilschifter","sequence":"additional","affiliation":[{"name":"Department of Neurology and Clinical Neurophysiology, Klinikum Lueneburg, Germany (W.P., M. Herrmann)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7530-818X","authenticated-orcid":true,"given":"Marialuisa","family":"Zedde","sequence":"additional","affiliation":[{"name":"Neurology Unit, Stroke Unit, Azienda Unit\u00e0 Sanitaria Locale-IRCCS di Reggio Emilia, Italy (M.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-5950","authenticated-orcid":true,"given":"Jo\u00e3o Pedro","family":"Marto","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centro Hospitalar Lisboa Ocidental, Hospital de Egas Moniz, Lisbon, Portugal (J.P.M., B.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2477-840X","authenticated-orcid":true,"given":"Paolo","family":"Candelaresi","sequence":"additional","affiliation":[{"name":"Neurology and Stroke Unit, A.O.R.N. Antonio Cardarelli, Napoli, Italy (P.C., E.S., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4948-5956","authenticated-orcid":true,"given":"Robin","family":"Lemmens","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Experimental Neurology, KU Leuven, Belgium (R.L., L.M.)."},{"name":"Department of Neurology, University Hospitals Leuven, Belgium (R.L., L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9419-4197","authenticated-orcid":true,"given":"Pasquale","family":"Scoppettuolo","sequence":"additional","affiliation":[{"name":"Neurology Department, Cliniques Universitaires Saint Luc-UCL, Bruxelles, Belgique (P.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Woock","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sahlgrenska University Hospital, G\u00f6teborg, Sweden (M.W., A.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5933-0985","authenticated-orcid":true,"given":"Pawel","family":"Kermer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nordwest-Krankenhaus Sanderbusch, Friesland Kliniken GmbH, Sande and University Medicine G\u00f6ttingen, Germany (P.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-5424","authenticated-orcid":true,"given":"Espen Saxhaug","family":"Kristoffersen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Akershus University Hospital, L\u00f8renskog, Norway (E.S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2350-284X","authenticated-orcid":true,"given":"Malik","family":"Ghannam","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Iowa Hospitals and Clinics (M.G., Q.N.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9494-160X","authenticated-orcid":true,"given":"Senta","family":"Frol","sequence":"additional","affiliation":[{"name":"Department of Vascular Neurology, University Medical Center Ljubljana, Faculty of Medicine, University of Ljubljana, Slovenia (S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5577-1775","authenticated-orcid":true,"given":"Christian H.","family":"Nolte","sequence":"additional","affiliation":[{"name":"Department of Neurology with Experimental Neurology and Center for Stroke Research, Charit\u00e9\u2013Universit\u00e4tsmedizin Berlin, Germany (C.H.N., C.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yakushiji","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kansai Medical University, Osaka, Japan (Y.Y., T.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-2162","authenticated-orcid":true,"given":"Emmanuel","family":"Touz\u00e9","sequence":"additional","affiliation":[{"name":"Department of Neurology, CHU de Caen Normandie, France (E.T., M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-0510","authenticated-orcid":true,"given":"Timo","family":"Uphaus","sequence":"additional","affiliation":[{"name":"Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany (T.U., M. Hahn)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-7235","authenticated-orcid":true,"given":"Marina","family":"Mannino","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Unit, AOOR Villa Sofia-V. 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C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-4283","authenticated-orcid":true,"given":"Carolina","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"Stroke Centre, Lisbon Central University Hospital Center\u2013ULS S\u00e3o Jos\u00e9, Portugal (D.A.d.S., M.E.M., C.G.)."},{"name":"CEEM e Instituto de Anatomia, Faculdade de Medicina, Universidade de Lisboa, Portugal (D.A.d.S., M.E.M., C.G.)."},{"name":"Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal (D.A.d.S., M.E.M., C.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Burini","sequence":"additional","affiliation":[{"name":"Clinical Neurology and Stroke Unit, Department of Head, Neck and Neurosciences, Udine University Hospital, Italy (G.M., A.B., L.C., 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Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3009-3765","authenticated-orcid":true,"given":"Antonia","family":"Kleeberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Heidelberg University Hospital, Germany (J.C.P., A.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Thevoz","sequence":"additional","affiliation":[{"name":"Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland (D.S., G.T., P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-7579","authenticated-orcid":true,"given":"Patrik","family":"Michel","sequence":"additional","affiliation":[{"name":"Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Switzerland (D.S., G.T., 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Lueneburg, Germany (W.P., M. Herrmann)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centro Hospitalar Lisboa Ocidental, Hospital de Egas Moniz, Lisbon, Portugal (J.P.M., B.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5123-2459","authenticated-orcid":true,"given":"Emanuele","family":"Spina","sequence":"additional","affiliation":[{"name":"Neurology and Stroke Unit, A.O.R.N. Antonio Cardarelli, Napoli, Italy (P.C., E.S., V.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Andreone","sequence":"additional","affiliation":[{"name":"Neurology and Stroke Unit, A.O.R.N. 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Alan","family":"Barber","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Auckland, New Zealand (P.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2077-8464","authenticated-orcid":true,"given":"Alan J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Whangarei Hospital, New Zealand (A.J.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1845-1769","authenticated-orcid":true,"given":"Teddy Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Christchurch Hospital, New Zealand (T.Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9177-2289","authenticated-orcid":true,"given":"Johannes","family":"Kaesmacher","sequence":"additional","affiliation":[{"name":"University Institute of Diagnostic and Interventional 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