{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:14:28Z","timestamp":1792599268068,"version":"4.5.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,3,7]]},"abstract":"\n Background<\/jats:title>\n \n In REDUCE\u2010IT (Reduction of Cardiovascular Events With Icosapent Ethyl\u2013Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization, but was associated with increased atrial fibrillation\/atrial flutter (AF) hospitalization (3.1% IPE versus 2.1% placebo;\n P<\/jats:italic>\n =0.004).\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We performed post hoc efficacy and safety analyses of patients with or\u00a0without\u00a0prior AF (before randomization) and\u00a0with\u00a0or without\u00a0in\u2010study time\u2010varying AF hospitalization to assess relationships of IPE (versus placebo) and outcomes. In\u2010study AF hospitalization event rates were higher in patients with prior AF (12.5% versus 6.3%, IPE versus placebo;\n P<\/jats:italic>\n =0.007) versus without prior AF (2.2% versus 1.6%, IPE versus placebo;\n P<\/jats:italic>\n =0.09). Serious bleeding rates trended higher in patients with (7.3% versus 6.0%, IPE versus placebo;\n P<\/jats:italic>\n =0.59) versus without prior AF (2.3% versus 1.7%, IPE versus placebo;\n P<\/jats:italic>\n =0.08). With IPE, serious bleeding trended higher regardless of prior AF (interaction\n P<\/jats:italic>\n value [\n P<\/jats:italic>\n int<\/jats:sub>\n ]=0.61) or postrandomization AF hospitalization (\n P<\/jats:italic>\n int<\/jats:sub>\n =0.66). Patients with prior AF (n=751, 9.2%) versus without prior AF (n=7428, 90.8%) had similar relative risk reductions of the primary composite and key secondary composite end points with IPE versus placebo (\n P<\/jats:italic>\n int<\/jats:sub>\n =0.37 and\n P<\/jats:italic>\n int<\/jats:sub>\n =0.55, respectively).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In REDUCE\u2010IT, in\u2010study AF hospitalization rates were higher in patients with prior AF especially in those randomized to IPE. Although serious bleeding trended higher in those randomized to IPE versus placebo over the course of the study, serious bleeding was not different regardless of prior AF or in\u2010study AF hospitalization. Patients with prior AF or in\u2010study AF hospitalization had consistent relative risk reductions across primary, key secondary, and stroke end points with IPE.<\/jats:p>\n <\/jats:sec>\n \n Registration<\/jats:title>\n \n URL:\n https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01492361<\/jats:ext-link>\n ; Unique Identifier: NCT01492361\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.121.026756","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T06:02:00Z","timestamp":1676959320000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillation in REDUCE\u2010IT"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-045X","authenticated-orcid":false,"given":"Brian","family":"Olshansky","sequence":"first","affiliation":[{"name":"Department of Medicine University of Iowa Iowa City IA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Heart Icahn School of Medicine at Mount Sinai Health System New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1679-2095","authenticated-orcid":false,"given":"Michael","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine Crescenz Veterans Affairs Medical Center and Hospital of the University of Pennsylvania Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-2941","authenticated-orcid":false,"given":"Ph. 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Bridgewater NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-7778","authenticated-orcid":false,"suffix":"Jr","given":"Ralph T.","family":"Doyle","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc. Bridgewater NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3714-6084","authenticated-orcid":false,"given":"Rebecca A.","family":"Juliano","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc. Bridgewater NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7003-4925","authenticated-orcid":false,"given":"Lixia","family":"Jiao","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc. Bridgewater NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-1638","authenticated-orcid":false,"given":"Peter R.","family":"Kowey","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research Wynnewood PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-1866","authenticated-orcid":false,"given":"James A.","family":"Reiffel","sequence":"additional","affiliation":[{"name":"Columbia University Vagelos College of Physicians & Surgeons New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8200-8983","authenticated-orcid":false,"given":"Jean\u2010Claude","family":"Tardif","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute, Universit\u00e9 de Montr\u00e9al Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6432-1730","authenticated-orcid":false,"given":"Christie M.","family":"Ballantyne","sequence":"additional","affiliation":[{"name":"Department of Medicine Baylor College of Medicine Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7835-6045","authenticated-orcid":false,"given":"Mina K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the REDUCE\u2010IT Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-020-00865-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000482"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.06.030"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.111.000547"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.28733"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.02.045"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018235"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.118.004584"},{"key":"e_1_3_2_10_2","article-title":"No impact of fish oil supplements on bleeding risk: a systematic review","volume":"64","author":"Begtrup KM","year":"2017","unstructured":"Begtrup KM, Krag AE, Hvas AM. 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