{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:52:03Z","timestamp":1791478323951,"version":"4.3.4"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2021,11,30]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135\u2013499 mg\/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo. Patients from REDUCE-IT were categorized by prespecified estimated glomerular filtration rate (eGFR) categories to analyze the effect of icosapent ethyl on the primary end point (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina) and key secondary end point (a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      (range, 17\u2013123 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      ). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and key secondary composite end points across baseline eGFR categories. Patients with eGFR &lt;60 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite end point (icosapent ethyl versus placebo, 21.8% versus 28.9%; hazard ratio [HR], 0.71 [95% CI, 0.59\u20130.85];\n                      <jats:italic>P<\/jats:italic>\n                      =0.0002) and key secondary composite end point (16.8% versus 22.5%; HR 0.71 [95% CI, 0.57\u20130.88];\n                      <jats:italic>P<\/jats:italic>\n                      =0.001). The numeric reduction in cardiovascular death was greatest in the eGFR &lt;60 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      group (icosapent ethyl: 7.6%; placebo: 10.6%; HR, 0.70 [95% CI, 0.51\u20130.95];\n                      <jats:italic>P<\/jats:italic>\n                      =0.02). Although patients with eGFR &lt;60 mL\u00b7min\n                      <jats:sup>\u20131<\/jats:sup>\n                      \u00b71.73 m\n                      <jats:sup>\u20132<\/jats:sup>\n                      treated with icosapent ethyl had the highest numeric rates of atrial fibrillation\/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42 [95% CI, 0.86\u20132.32];\n                      <jats:italic>P<\/jats:italic>\n                      =0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR, 1.40 [95% CI, 0.90\u20132.18];\n                      <jats:italic>P<\/jats:italic>\n                      =0.13), HRs for atrial fibrillation\/flutter and serious bleeding were similar across eGFR categories (\n                      <jats:italic>P<\/jats:italic>\n                      -interaction for atrial fibrillation\/flutter=0.92;\n                      <jats:italic>P<\/jats:italic>\n                      -interaction for serious bleeding=0.76).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>REGISTRATION:<\/jats:bold>\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: NCT01492361\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.121.055560","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T05:00:20Z","timestamp":1635397220000},"page":"1750-1759","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":72,"title":["Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL"],"prefix":"10.1161","volume":"144","author":[{"given":"Arjun","family":"Majithia","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, Lahey Hospital and Medical Center, Burlington, MA (A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":true,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA (D.L.B., R.P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allon N.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Indiana University School of Medicine, Indianapolis (A.N.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1679-2095","authenticated-orcid":true,"given":"Michael","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Maryland School of Medicine, Baltimore (M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-2941","authenticated-orcid":true,"given":"Ph. Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, FACT (French Alliance for Cardiovascular Trials), Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Bichat, INSERM Unit\u00e9 1148, France (P.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-4010","authenticated-orcid":true,"given":"Eliot A.","family":"Brinton","sequence":"additional","affiliation":[{"name":"Utah Lipid Center, Salt Lake City (E.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta, GA (T.A.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Ketchum","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc., Bridgewater, NJ (S.B.K., R.A.J., 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