{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:29:46Z","timestamp":1791563386275,"version":"4.3.4"},"reference-count":52,"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":[[2025,3,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The efficacy of icosapent ethyl among patients with very well\u2010controlled baseline low\u2010density lipoprotein cholesterol (LDL\u2010C) is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">In this post hoc analysis of the REDUCE\u2010IT (Reduction of Cardiovascular Events With Icosapent Ethyl\u2013Intervention Trial) randomized clinical trial, statin\u2010treated patients with high cardiovascular risk, elevated triglycerides (135\u2013499\u2009mg\/dL), and baseline LDL\u2010C of 41 to 100\u2009mg\/dL were included. Patients were randomized to icosapent ethyl (2\u2009g twice daily) or placebo and then post hoc stratified by baseline LDL\u2010C (&lt;55\u2009mg\/dL versus \u226555\u2009mg\/dL). The primary composite end point included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Among 8175 patients with baseline LDL\u2010C data, 7117 (87.1%) had LDL\u2010C \u226555\u2009mg\/dL and 1058 (12.9%) had LDL\u2010C &lt;55\u2009mg\/dL. In patients with LDL\u2010C &lt;55\u2009mg\/dL, the rate of the primary composite end point was lower in the icosapent ethyl group (16.2% versus 22.8%) than in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50\u20130.87]; absolute risk reduction, 6.6%;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.003). Among patients with LDL\u2010C \u226555\u2009mg\/dL, a primary composite end point event occurred in a lower proportion of patients in the icosapent ethyl group (17.4% versus 21.9%) than in the placebo group (HR, 0.76 [95% CI, 0.69\u20130.85]; absolute risk reduction, 4.5%;\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.0001). No significant interaction was observed between baseline LDL\u2010C and treatment group (\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      for interaction=0.40). Findings were consistent among secondary cardiovascular end points and in sensitivity analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Among statin\u2010treated patients with elevated triglycerides and high cardiovascular risk, icosapent ethyl reduced the rate of cardiovascular end points irrespective of baseline LDL\u2010C, including among eligible patients with optimal LDL\u2010C control.<\/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=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT01492361.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.038656","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T06:34:06Z","timestamp":1739946846000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Cardiovascular Outcomes With Icosapent Ethyl by Baseline Low\u2010Density Lipoprotein Cholesterol: A Secondary Analysis of the REDUCE\u2010IT Randomized Trial"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4746-8511","authenticated-orcid":false,"given":"Rahul","family":"Aggarwal","sequence":"first","affiliation":[{"name":"Harvard Medical School","place":["Boston"]}],"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 Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-2941","authenticated-orcid":false,"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","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1679-2095","authenticated-orcid":false,"given":"Michael","family":"Miller","sequence":"additional","affiliation":[{"name":"Crescenz Veterans Affairs Medical Center and University of Pennsylvania School of Medicine","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-4010","authenticated-orcid":false,"given":"Eliot A.","family":"Brinton","sequence":"additional","affiliation":[{"name":"Utah Lipid Center","place":["Salt Lake City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-4794","authenticated-orcid":false,"given":"Richard L.","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc.","place":["Bridgewater"]},{"name":"Perelman School of Medicine at the University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9302-4743","authenticated-orcid":false,"given":"Steven B.","family":"Ketchum","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc.","place":["Bridgewater"]}],"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","place":["Montreal, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0977-7276","authenticated-orcid":false,"given":"Fabrice M. A. C.","family":"Martens","sequence":"additional","affiliation":[{"name":"Amsterdam UMC","place":["Amsterdam, The Netherlands"]}],"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":"Baylor College of Medicine, and the Texas Heart Institute","place":["Houston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-0264","authenticated-orcid":false,"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine","place":["Aurora"]},{"name":"CPC Clinical Research","place":["Aurora"]},{"name":"State University of New York, Downstate Health Sciences University","place":["Brooklyn"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-1852","authenticated-orcid":false,"given":"R. Preston","family":"Mason","sequence":"additional","affiliation":[{"name":"Harvard Medical School","place":["Boston"]},{"name":"Elucida Research LLC","place":["Beverly"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"REDUCE\u2010IT Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.115.002104"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.04.059"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1812792"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-012-0002-3"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.034076"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.124.319570"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313286"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2021.08.003"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.02.032"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.02.035"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.044440"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.055560"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056290"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.022937"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.050276"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz455"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.07.006"},{"key":"e_1_3_1_19_2","volume-title":"Clinical Methods: the History, Physical, and Laboratory Examinations","author":"Cox RA","year":"1990","unstructured":"Cox RA, Garc\u00eda\u2010Palmieri MR. Cholesterol, triglycerides, and associated lipoproteins. In: Walker HK, Hall WD, Hurst JW, eds Clinical Methods: the History, Physical, and Laboratory Examinations. Butterworths; 1990. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK351\/"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.22692"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000625"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/18.6.499"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.280532"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107039"},{"key":"e_1_3_1_25_2","unstructured":"SAS [Internet]. www.SAS.com."},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1912387"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801174"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.11.005"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.48172"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.032413"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad668"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpc.2022.100345"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad889"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.12567"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-12-100"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.06.043"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahjo.2022.100148"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210645"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.22258"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107579"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht055"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.061"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-022-01075-x"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2022.102450"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad188"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehaa652"},{"key":"e_1_3_1_48_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2023.2731"},{"key":"e_1_3_1_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjci\/jead063"},{"key":"e_1_3_1_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60527-3"},{"key":"e_1_3_1_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.065520"},{"key":"e_1_3_1_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad655.1309"},{"key":"e_1_3_1_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2021.100997"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.038656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:39:13Z","timestamp":1788874753000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.038656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,4]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,3,4]]}},"alternative-id":["10.1161\/JAHA.124.038656"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.038656","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,4]]},"assertion":[{"value":"2024-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e038656"}}