{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:13:00Z","timestamp":1788430380354,"version":"build-2803163510"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"\n Importance<\/jats:title>\n \n The\n APOE<\/jats:italic>\n \u03b54 variant is causally linked to cerebral amyloid angiopathy and is a risk factor for intracranial hemorrhage (ICH) among warfarin-treated patients with atrial fibrillation. Nevertheless, its impact on those treated with apixaban remains unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To test the hypothesis that\n APOE<\/jats:italic>\n \u03b54 allele carriership is associated with an increased risk of ICH in patients with atrial fibrillation taking apixaban.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cohort study involved data from the All of Us Research Program, a longitudinal, population-based study in the United States. Inclusion criteria were age older than 50 years, history of atrial fibrillation, and anticoagulation with apixaban. Participants with a history of ischemic stroke or ICH were excluded. Up to 3 years of follow-up data were available. Data were collected from 2017 to 2022 and analyzed from November 2023 to December 2024.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n APOE<\/jats:italic>\n \u03b52, \u03b53, and \u03b54 were ascertained using variants rs429358 and rs7412.\n APOE<\/jats:italic>\n \u03b54 was modeled dichotomously (noncarriers [no alleles] vs carriers [1 or 2 alleles]).\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Incident ICH, including any new intraparenchymal, subdural, or subarachnoid hemorrhage after initiation of apixaban therapy.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 413\u202f477 All of Us participants, 2038 were eligible. Their mean (SD) age was 71 (9) years; 918 (45%) were female, 1120 (55%) were male, and 1710 (83%) had European ancestry. Among these participants, 483 (23.7%) were carriers of at least 1\n APOE<\/jats:italic>\n \u03b54 allele. After a median follow-up of 2.9 years, 26 participants sustained an ICH (cumulative incidence, 1.5%; 95% CI, 1.0%-2.2%), of whom 12 (cumulative incidence, 3.1%; 95% CI, 1.7%-5.3%) were carriers and 14 (cumulative incidence, 1%; 95% CI, 0.6%-1.7%) were noncarriers (\n P<\/jats:italic>\n \u2009=\u2009.007). Multivariable Cox proportional hazard models confirmed this association: compared with noncarriership,\n APOE<\/jats:italic>\n \u03b54 carriership was associated with a 3-fold increase in the risk of ICH (hazard ratio, 3.07; 95% CI, 1.42-6.65).\n APOE<\/jats:italic>\n information improved the discrimination of risk prediction scores (C statistic of 0.74 and 0.68 for models with and without\n APOE<\/jats:italic>\n , respectively;\n P<\/jats:italic>\n \u2009=\u2009.03).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n Further research is needed to evaluate whether cerebral amyloid angiopathy mediates the observed association and whether\n APOE<\/jats:italic>\n e4 information improves clinical decision-making about anticoagulation therapy in patients with atrial fibrillation. The latter is important now that\n APOE<\/jats:italic>\n information is used in clinical settings to guide antiamyloid treatment for Alzheimer disease and has been returned to millions of persons by direct-to-consumer genotyping companies.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.0182","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T11:30:59Z","timestamp":1750678259000},"page":"808","source":"Crossref","is-referenced-by-count":5,"title":["APOE<\/i>\n \u03b54 and Risk of Intracranial Hemorrhage in Patients With Atrial Fibrillation Taking Apixaban"],"prefix":"10.1001","volume":"82","author":[{"given":"Santiago","family":"Clocchiatti-Tuozzo","sequence":"first","affiliation":[{"name":"Department of Neurology, Yale School of Medicine, New Haven, Connecticut"},{"name":"Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut"},{"name":"Department of Internal Medicine, Yale School of Medicine, New Haven, 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