{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:13:54Z","timestamp":1788912834644,"version":"build-2803163510"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Andexanet improves hemostatic efficacy in FXa (factor Xa) inhibitor\u2013associated intracranial hemorrhage but carries a risk of thrombotic events. These secondary analyses of the ANNEXA-I trial (A Randomized Clinical Trial of Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor) examined determinants of hematoma expansion (HE) and the corresponding response to andexanet.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>ANNEXA-I enrolled patients aged \u226518 years with acute FXa inhibitor\u2013associated intracranial hemorrhage within 6 hours of onset between June 6, 2019, and May 27, 2023, at 131 sites in 23 countries. Participants were randomized (1:1) to andexanet or usual care. Among 530 participants, 459 (87%) had a qualifying intracerebral hemorrhage and adequate brain imaging for these analyses. The primary outcome was HE (\u226512.5-mL or \u226535% increase in baseline volume) at 12 hours. We report differences in the proportion of HE between treatment groups stratified by variables significantly associated with HE in regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>HE occurred in 149 of 459 participants (32.5%). Symptom onset-to-treatment time (adjusted odds ratio per hour, 0.73 [95% CI, 0.63\u20130.85]), baseline hematoma volume (adjusted odds ratio per 10 mL, 1.11 [95% CI, 1.01\u20131.23]), and diastolic blood pressure (adjusted odds ratio per 10 mm\u2009Hg, 1.15 [95% CI, 1.02\u20131.29]) were associated with HE but not thrombotic events. In a separate multivariable model replacing volume and onset-to-treatment time with prescan hematoma growth rate, growth rate was also associated with HE (adjusted odds ratio per mL\/h, 1.02 [95% CI, 1.01\u20131.04]). Patients in the highest risk quartiles (baseline volume &gt;22.4 mL, growth rate &gt;11.4 mL\/h, diastolic blood pressure &gt;95.0 mm\u2009Hg, and onset-to-treatment time \u22643.3 hours) had \u224850% to 60% absolute risk of HE with usual care. Numerically greater absolute risk reductions with andexanet (\u224825%; number needed to treat: 4) were observed in the highest quartiles of baseline volume and growth rate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Shorter onset-to-treatment time, larger baseline hematoma volume, higher diastolic blood pressure, and higher prescan hematoma growth rate predict HE but not thrombotic events in FXa inhibitor\u2013associated intracerebral hemorrhage. Andexanet benefit is observed across these ranges and may be amplified through patient selection using these metrics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03661528.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.124.050418","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T09:00:22Z","timestamp":1778144422000},"page":"1920-1928","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Predictors of Hematoma Expansion and Response to Andexanet in Patients With Intracerebral Hemorrhage: Secondary Analyses of the ANNEXA-I Randomized Clinical Trial"],"prefix":"10.1161","volume":"57","clinical-trial-number":[{"clinical-trial-number":"nct03661528","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2802-1626","authenticated-orcid":true,"given":"Ashkan","family":"Shoamanesh","sequence":"first","affiliation":[{"name":"Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (A.S., S.J.C., L.X., M.C., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7377-335X","authenticated-orcid":true,"given":"Stuart J.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (A.S., S.J.C., L.X., M.C., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4930-7789","authenticated-orcid":true,"given":"Andrew M.","family":"Demchuk","sequence":"additional","affiliation":[{"name":"Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada (A.M.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3890-3849","authenticated-orcid":true,"given":"David J.","family":"Seiffge","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital University Hospital and University of Bern, Switzerland (D.J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4312-4778","authenticated-orcid":true,"given":"Else Charlotte","family":"Sandset","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oslo University Hospital and the Norwegian Air Ambulance Foundation, Norway (E.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6058-6259","authenticated-orcid":true,"given":"Carlos A.","family":"Molina","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vall d\u2019Hebron Stroke Center, Autonomous University of Barcelona, Spain (C.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0640-3797","authenticated-orcid":true,"given":"Georgios","family":"Tsivgoulis","sequence":"additional","affiliation":[{"name":"Second Department of Neurology, National and Kapodistrian University of Athens, Attikon University Hospital, Greece (G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7472-3194","authenticated-orcid":true,"given":"Hanne","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Copenhagen University Hospital, Bispebjerg Hospital, Denmark (H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6983-9993","authenticated-orcid":true,"given":"Jan","family":"Beyer-Westendorf","sequence":"additional","affiliation":[{"name":"Division of Thrombosis &amp; Hemostasis, Department of Medicine 1, University Hospital Dresden, Germany (J.B.-W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-982X","authenticated-orcid":true,"given":"Jonathan M.","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, the Netherlands (J.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3842-1236","authenticated-orcid":true,"given":"Pierre","family":"Amarenco","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Centre, Bichat Claude-Bernard Hospital, Paris, France (P.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\u2013University of Leuven, Belgium (R.L.)."},{"name":"Department of Neurology, University Hospitals Leuven, Belgium (R.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-1300","authenticated-orcid":true,"given":"Roland","family":"Veltkamp","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College, London, United Kingdom (R.V.)."},{"name":"Neurology Clinic, Alfried Krupp Krankenhaus, Essen, Germany (R.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1006-6420","authenticated-orcid":true,"given":"Saskia","family":"Middeldorp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (S.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-4507","authenticated-orcid":true,"given":"Andrea","family":"Zini","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, IRCCS Istituto delle Scienze Neurologiche di Bologna, Maggiore Hospital, Bologna, Italy (A.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Himmelmann","sequence":"additional","affiliation":[{"name":"AstraZeneca Biopharmaceuticals Research and Development, Late-Stage Development, Cardiovascular, Renal, and Metabolism (CVRM), Gothenburg, Sweden (A.H., P.L., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0300-8070","authenticated-orcid":true,"given":"Per","family":"Ladenvall","sequence":"additional","affiliation":[{"name":"AstraZeneca Biopharmaceuticals Research and Development, Late-Stage Development, Cardiovascular, Renal, and Metabolism (CVRM), Gothenburg, Sweden (A.H., P.L., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Knutsson","sequence":"additional","affiliation":[{"name":"AstraZeneca Biopharmaceuticals Research and Development, Late-Stage Development, Cardiovascular, Renal, and Metabolism (CVRM), Gothenburg, Sweden (A.H., P.L., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (A.S., S.J.C., L.X., M.C., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Crowther","sequence":"additional","affiliation":[{"name":"Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (A.S., S.J.C., L.X., M.C., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-342X","authenticated-orcid":true,"given":"Mukul","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada (A.S., S.J.C., L.X., M.C., M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the ANNEXA-I Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25342"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.027882"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207728"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182143317"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000208408.98482.99"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1814051"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057844"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2313040"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30253-9"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182343387"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002897"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26795"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c869"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-4949.2010.00579.x"},{"key":"e_1_3_3_16_2","unstructured":"Seiffge D Sandset EC Shoamanesh A Sharma M Xu L Andersson M Ladenvall P Connolly S; ANNEXA-I Investigators. Clinical consequences of haematoma expansion and thrombotic events in patients with factor Xa Inhibitor\u2013associated ICH in ANNEXA-I. Paper presented at: The European Stroke Organisation Conference (ESOC); May 15 2024; Basel Switzerland."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00806-1"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.043033"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/23969873231220235"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.124.050418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T19:37:40Z","timestamp":1785958660000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.124.050418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":18,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1161\/STROKEAHA.124.050418"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.124.050418","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2024-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}