{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:47:03Z","timestamp":1779151623350,"version":"3.51.4"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,2,24]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Systemic embolic events (SEEs) are a serious but underrecognized complication of atrial fibrillation. Although non\u2013vitamin K antagonist oral anticoagulants prevent ischemic stroke (IS), their efficacy in SEE and the clinical characteristics of patients who experience SEE remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We analyzed individual patient data from 4 pivotal randomized trials enrolling patients between 2005 and 2010 comparing non\u2013vitamin K antagonist oral anticoagulants versus warfarin in atrial fibrillation. We characterized the incidence, clinical features, management, and outcomes of clinically overt SEE and compared results in these patients with patients who had an IS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Among 71\u2009683 patients, 188 experienced SEE (26 with concurrent IS), yielding an annualized event rate of 0.13% per patient-year, compared with 1.25% per patient-year for IS (n=1797). Among 171 patients with SEE as their first event, median age was 75 years (interquartile range, 68\u201380), 49.7% were female, and mean\u00b1SD CHA\n                      <jats:sub>2<\/jats:sub>\n                      DS\n                      <jats:sub>2<\/jats:sub>\n                      -VASc score was 4.\n                      <jats:underline>7<\/jats:underline>\n                      \u00b11.5. Compared with IS, patients with SEE had higher rates of peripheral arterial disease (PAD, 16.5% versus 5.4%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), previous myocardial infarction (24% versus 17%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.02), previous vitamin K antagonist exposure (57% versus 46%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.007), worse renal function (median creatinine clearance 58 versus 62 mL\/min;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.02), and higher incidence of nonparoxysmal atrial fibrillation (86% versus 80%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.047). Interventions (surgical or percutaneous) were performed in 62 patients (31%) with SEE. Standard-dose non\u2013vitamin K antagonist oral anticoagulants reduced the risk of SEE by 29% compared with warfarin over a median follow-up of 25.2 months (interquartile range, 17.5\u201332.0; hazard ratio, 0.71 [95% CI, 0.51\u20130.99];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.04). Thirty-day mortality after SEE was similar to IS (18% versus 17%), and SEE was associated with a nearly 3-fold increased risk of long-term mortality compared with patients without SEE or IS (hazard ratio, 2.85 [95% CI, 2.11\u20133.85]). Independent predictors of SEE included peripheral artery disease, smoking, nonparoxysmal atrial fibrillation, female sex, previous myocardial infarction, previous stroke or transient ischemic attack, vitamin K antagonist experience, and renal dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In this large individual patient data meta-analysis, non\u2013vitamin K antagonist oral anticoagulants significantly reduced the risk of SEE compared with warfarin. Although SEEs were approximately one-tenth as frequent as IS, they were associated with comparable mortality and substantial morbidity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.075275","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T10:00:12Z","timestamp":1769767212000},"page":"567-575","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Systemic Embolic Events in Atrial Fibrillation: An Individual Patient Data Meta-analysis of 71 683 Participants Randomized to NOAC Versus Warfarin"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3262-3785","authenticated-orcid":true,"given":"Samer","family":"Al Said","sequence":"first","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.A.S., E.B., M.G.P., G.E.M.M., C.T.R., E.M.A., R.P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Braunwald","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.A.S., E.B., M.G.P., G.E.M.M., C.T.R., E.M.A., R.P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2128-6752","authenticated-orcid":true,"given":"Michael G.","family":"Palazzolo","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.A.S., E.B., M.G.P., G.E.M.M., C.T.R., E.M.A., R.P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-1334","authenticated-orcid":true,"given":"Giorgio E.M.","family":"Melloni","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.A.S., E.B., M.G.P., G.E.M.M., C.T.R., E.M.A., R.P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0767-5102","authenticated-orcid":true,"given":"Bram J.","family":"Geller","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Maine Medical Center, Portland (B.J.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4712-3206","authenticated-orcid":true,"given":"Christian T.","family":"Ruff","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.A.S., E.B., M.G.P., G.E.M.M., C.T.R., E.M.A., R.P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliott M.","family":"Antman","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.A.S., E.B., M.G.P., G.E.M.M., C.T.R., E.M.A., R.P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-4562","authenticated-orcid":true,"given":"Anthony P.","family":"Carnicelli","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston (A.P.C.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4126-1285","authenticated-orcid":true,"given":"John W.","family":"Eikelboom","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, Canada (J.W.E.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0045-3291","authenticated-orcid":true,"given":"Christopher B.","family":"Granger","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University, Durham, NC (C.B.G., M.R.P)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2393-0855","authenticated-orcid":true,"given":"Manesh R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University, Durham, NC (C.B.G., M.R.P)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0378-6531","authenticated-orcid":true,"given":"Lars","family":"Wallentin","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Sweden (L.W.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-7675","authenticated-orcid":true,"given":"Robert P.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (S.A.S., E.B., M.G.P., G.E.M.M., C.T.R., E.M.A., R.P.G.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001193"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa612"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018172"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.161.2.272"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2015.06.020"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013243"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0905561"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009638"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1310907"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056355"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62343-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2020.12.002"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1109\/tac.1974.1100705"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.cd008980.pub3"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12181"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.553438"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2007.135657"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68845-4"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.125.075275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T19:00:30Z","timestamp":1772737230000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.125.075275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":19,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,2,24]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.125.075275"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.125.075275","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"assertion":[{"value":"2025-04-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}