{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T11:44:54Z","timestamp":1767008694635,"version":"3.41.2"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation\u2013Thrombolysis in Myocardial Infarction 48 (ENGAGE AF\u2010TIMI 48) randomized 21\u2009105 patients with atrial fibrillation and CHADS2 risk score \u22652 to higher\u2010dose edoxaban regimen (60\u2009mg daily, dose\u2010reduced to 30 mg), lower\u2010dose edoxaban regimen (30\u2009mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria. Patients with intracranial hemorrhage during follow\u2010up were excluded; those with &gt;1 bleeding event were categorized according to their most severe event. The safety cohort with interval censoring during drug interruption was analyzed. Proportions were compared using Pearson's chi\u2010square test and treatment arms were compared using a Cox proportional hazards model. Among 5247 patients with a bleeding event, 1008 (19.2%) had epistaxis and 4239 (80.8%) had nonepistaxis bleeding. Epistaxis events were less severe than nonepistaxis bleeds (International Society on Thrombosis and Haemostasis major: 3.2% versus 20.7%; clinically relevant nonmajor: 64.7% versus 60.1%; minor: 32.1% versus 19.2%;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Permanent drug discontinuation was similar following epistaxis versus nonepistaxis bleeding in patients with major (59.4% versus 53.6%;\n              <jats:italic>P<\/jats:italic>\n              =0.52) or clinically relevant nonmajor (32.5% versus 33.3%;\n              <jats:italic>P<\/jats:italic>\n              =0.70) bleeding but was significantly higher in patients with minor epistaxis versus other minor bleeds (33.3% versus 23.9%;\n              <jats:italic>P<\/jats:italic>\n              =0.001). Compared with warfarin, higher\u2010dose edoxaban regimen had similar risk of epistaxis (hazard ratio [HR], 1.09 [95% CI, 0.95\u20131.26]), whereas lower\u2010dose edoxaban regimen conferred reduced risk (HR, 0.73 [95% CI, 0.62\u20130.86]).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Epistaxis was frequent, and despite being overall less severe than nonepistaxis bleeding, was associated with similar rates of anticoagulant discontinuation. Compared with warfarin, lower\u2010dose edoxaban regimen reduced the risk of epistaxis by 27% whereas higher\u2010dose edoxaban regimen had no effect.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">https:\/\/clinicaltrials.gov<\/jats:ext-link>\n              ; Unique Identifier:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/show\/NCT00781391\">NCT00781391<\/jats:ext-link>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.031434","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T11:17:10Z","timestamp":1736507830000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Epistaxis Versus Nonepistaxis Bleeding in Anticoagulated Patients With Atrial Fibrillation: Results From the ENGAGE AF\u2010TIMI 48 Trial"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4696-3123","authenticated-orcid":false,"given":"Robert S.","family":"Semco","sequence":"first","affiliation":[{"name":"Center for Surgery and Public Health Brigham and Women\u2019s Hospital Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3249-4343","authenticated-orcid":false,"given":"Regan W.","family":"Bergmark","sequence":"additional","affiliation":[{"name":"Center for Surgery and Public Health Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Division of Otolaryngology\u2010Head and Neck Surgery, Department of Surgery Brigham and Women\u2019s Hospital and Dana Farber Cancer Institute Boston MA USA"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8231-3611","authenticated-orcid":false,"given":"Sabina A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division Brigham and Women\u2019s Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abby L.","family":"Cange","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division Brigham and Women\u2019s Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-8187","authenticated-orcid":false,"given":"Martin","family":"Unverdorben","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Edison NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1117-8085","authenticated-orcid":false,"given":"Cathy Z. L.","family":"Chen","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Edison NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4712-3206","authenticated-orcid":false,"given":"Christian T.","family":"Ruff","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division Brigham and Women\u2019s Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0808-9199","authenticated-orcid":false,"given":"Elliott M.","family":"Antman","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division Brigham and Women\u2019s Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-7675","authenticated-orcid":false,"given":"Robert P.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division Brigham and Women\u2019s Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-7606","authenticated-orcid":false,"given":"Brian A.","family":"Bergmark","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division Brigham and Women\u2019s Hospital and Harvard Medical School Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2004.12.014"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2019344"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.4193\/Rhin17.105"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-016-3913-9"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2014.09.009"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/lary.29417"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215113000492"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215110001921"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215115003424"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-020-05875-2"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009638"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041346"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310907"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2010.06.042"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2020.10.036"},{"key":"e_1_3_1_19_2","unstructured":"Bristol\u2010Myers Squibb Company and Pfizer . 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