{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:16:04Z","timestamp":1792556164674,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Remnant cholesterol and very low-density lipoprotein cholesterol (VLDL-C) are increasingly recognized risk factors for atherosclerotic disease with few therapeutic options. Angiopoietin-like 3 (ANGPTL3), a key protein in the metabolism of triglyceride-rich lipoproteins, is a promising target.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>TRANSLATE-TIMI 70 was a double-blind, placebo-controlled randomized trial testing seven dose regimens of vupanorsen, an antisense oligonucleotide against ANGPTL3, in adults with non-HDL-C \u2265 100\u2005mg\/dL and triglycerides 150\u2013500\u2005mg\/dL. The primary endpoint of this analysis was percentage change in remnant cholesterol (total cholesterol minus directly measured LDL-C minus HDL-C) and VLDL-C (directly measured) over 24 weeks. Two hundred eighty-six patients were enrolled, with a median age of 64 years and 44% female. Median baseline remnant cholesterol and VLDL-C were 42 and 31\u2005mg\/dL, respectively (reference: &amp;lt;30\u2005mg\/dL). Vupanorsen lowered remnant cholesterol by 42\u201359% at 24 weeks over placebo (P &amp;lt; 0.001), achieving a median level of 18\u2005mg\/dL at the highest dose. Over the same period, VLDL-C was reduced by 52\u201367% over placebo (P &amp;lt; 0.001), with a median achieved level of 2.5\u2005mg\/dL at the highest dose. The effect of vupanorsen on remnant cholesterol and VLDL-C reduction was dose-dependent and directly associated with the degree of ANGPTL3 inhibition: at 90% ANGPTL3 reduction, there was a 61% and 81% decrease in remnant cholesterol and VLDL-C, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Inhibition of ANGPTL3 protein synthesis significantly lowered remnant cholesterol and VLDL-C in patients with hypertriglyceridaemia. The magnitude of reduction was associated with the degree of ANGPTL3 inhibition. These findings support ANGPTL3 inhibition as a promising target for lowering cholesterol on triglyceride-rich lipoproteins.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwae090","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T21:40:40Z","timestamp":1710452440000},"page":"1216-1223","source":"Crossref","is-referenced-by-count":28,"title":["Reductions in remnant cholesterol and VLDL cholesterol through inhibition of ANGPTL3 protein synthesis: an analysis from the TRANSLATE-TIMI 70 trial"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-6929","authenticated-orcid":false,"given":"Andre","family":"Zimerman","sequence":"first","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women\u2019s Hospital, Harvard Medical School , 7th Floor, 60 Fenwood Road, Boston, MA 02115 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen 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