{"id":139772,"date":"2026-03-31T20:11:30","date_gmt":"2026-04-01T00:11:30","guid":{"rendered":"https:\/\/cardiologynownews.org\/?p=139772"},"modified":"2026-03-31T20:11:32","modified_gmt":"2026-04-01T00:11:32","slug":"intensive-triglyceride-lowering-with-olezarsen-does-not-reduce-coronary-plaque-progression-in-the-essence-timi-73b-ccta-sub-study","status":"publish","type":"post","link":"https:\/\/cardiologynownews.org\/?p=139772","title":{"rendered":"Intensive Triglyceride Lowering\u00a0with\u00a0Olezarsen\u00a0Does Not Reduce Coronary Plaque Progression in\u00a0the\u00a0Essence-TIMI 73b CCTA\u00a0Sub Study\u00a0"},"content":{"rendered":"\n<p>Key Points&nbsp;<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>In this sub study of coronary computed tomography angiography (CCTA) within Essence-TIMI 73b trial, olezarsen\u00a0produced profound reductions in triglycerides (~64%) and remnant cholesterol but minimal LDL-C change.\u00a0<\/li>\n\n\n\n<li>Despite robust lipid effects, there was\u00a0no significant reduction in non-calcified plaque volume\u00a0at 12 months.\u00a0<\/li>\n\n\n\n<li>No meaningful differences were\u00a0observed\u00a0in low-attenuation (high-risk) plaque or other plaque subtypes.\u00a0<\/li>\n\n\n\n<li>Findings challenge the assumption that targeting triglyceride-rich lipoproteins\u00a0(TRLs)\u00a0alone\u00a0modifies\u00a0coronary atherosclerosis over short-term follow-up.\u00a0<\/li>\n<\/ul>\n\n\n\n<p>Triglyceride-rich lipoproteins (TRLs) and remnant cholesterol have been increasingly implicated in atherosclerotic cardiovascular disease risk, with some data suggesting they may confer risk independent of LDL cholesterol. Apolipoprotein C-III (APOC3) regulates TRL metabolism, and genetic loss-of-function variants are associated with lower triglycerides and reduce coronary artery disease risk.&nbsp;Olezarsen, an antisense oligonucleotide targeting APOC3, has&nbsp;demonstrated&nbsp;potent triglyceride-lowering effects. However, whether this translates into structural changes in coronary atherosclerosis&nbsp;remains&nbsp;uncertain.&nbsp;<\/p>\n\n\n\n<p>The&nbsp;Essence-TIMI 73b trial (<a href=\"https:\/\/clinicaltrials.gov\/study\/NCT05610280\">NCT05610280<\/a>;&nbsp;N&nbsp;=&nbsp;1478) randomized patients with moderate-to-severe hypertriglyceridemia and elevated cardiovascular risk to&nbsp;olezarsen&nbsp;(50 mg&nbsp;or&nbsp;80 mg&nbsp;subcutaneously every 4 weeks) versus placebo. The study design was published in <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0002870325000729?via%3Dihub\">American Heart Journal<\/a> and the results of the main trial in &nbsp;<ins><a href=\"https:\/\/www.nejm.org\/doi\/10.1056\/NEJMoa2507227?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub%20%200pubmed\">NEJM<\/a><\/ins> in 2025.<ins><\/ins><\/p>\n\n\n\n<p>The coronary CTA&nbsp;sub study&nbsp;included 468 patients with quantifiable non-calcified plaque volume (NCPV) at baseline and follow-up imaging at 12 months. The primary endpoint was placebo-adjusted percent change in NCPV; key secondary endpoints included low-attenuation plaque volume (LAPV) and other plaque components. Approximately 400 paired scans were targeted for adequate power. This sub study was simultaneously published in <a href=\"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.126.080012\">Circulation<\/a>.<\/p>\n\n\n\n<p>Olezarsen&nbsp;significantly reduced triglycerides by&nbsp;~64% (absolute reduction ~132 mg\/dL), with parallel reductions in remnant cholesterol (~61%), VLDL-C (~72%), and modest reductions in apolipoprotein B (~16%), while LDL-C remained&nbsp;largely unchanged.&nbsp;<\/p>\n\n\n\n<p>Despite these favorable biomarker changes, the primary imaging endpoint was neutral: placebo-adjusted change in NCPV was +3.0% (95% CI&nbsp;-3.36 to 9.33; p=0.36). Similarly, there was no significant effect on LAPV (-68.2% relative difference;&nbsp;p=0.50) or other plaque subtypes including fibrous, fibrofatty, and calcified components. Notably, plaque progression in the placebo group was minimal,&nbsp;likely reflecting&nbsp;high baseline use of standard lipid-lowering therapies.&nbsp;<\/p>\n\n\n\n<p>This&nbsp;sub study&nbsp;highlights a potential disconnect between triglyceride lowering and short-term modification of coronary plaque burden. While APOC3 inhibition robustly improves atherogenic lipid profiles, these changes did not translate into measurable differences in coronary atherosclerosis over 12 months. The findings suggest that TRL and remnant cholesterol reduction alone may not exert rapid structural benefits comparable to LDL-C lowering, or that longer treatment duration may be&nbsp;required.&nbsp;<\/p>\n\n\n\n<p>Limitations include&nbsp;relatively short&nbsp;follow-up, reliance on CCTA rather than intravascular imaging, and a well-treated population with limited plaque progression. Importantly, genetic data linking APOC3 to lifetime cardiovascular risk reduction&nbsp;leaves&nbsp;open&nbsp;the possibility that longer-term outcomes may differ.&nbsp;As&nbsp;presented by Nicholas Marston, MD,&nbsp;\u201cThese data do not support the hypothesis that reductions in remnant cholesterol and TRLs have an outsized cardiovascular benefit compared with reductions in LDL-C.\u201d&nbsp;<\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Key Points&nbsp; Triglyceride-rich lipoproteins (TRLs) and remnant cholesterol have been increasingly implicated in atherosclerotic cardiovascular disease risk, with some data suggesting they may confer risk independent of LDL cholesterol. Apolipoprotein C-III (APOC3) regulates TRL metabolism, and genetic loss-of-function variants are associated with lower triglycerides and reduce coronary artery disease risk.&nbsp;Olezarsen, an antisense oligonucleotide targeting APOC3, [&hellip;]<\/p>\n","protected":false},"author":40613,"featured_media":139679,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"aside","meta":{"footnotes":""},"categories":[1074,8],"tags":[1075,45,47,185],"ppma_author":[1067],"class_list":{"0":"post-139772","1":"post","2":"type-post","3":"status-publish","4":"format-aside","5":"has-post-thumbnail","7":"category-acc-2026","8":"category-news","9":"tag-acc-2026","10":"tag-conference","11":"tag-featured","12":"tag-news","13":"post_format-post-format-aside","14":"author-oludamilola-aladesanmi-md"},"authors":[{"term_id":1067,"user_id":40613,"is_guest":0,"slug":"oludamilola-aladesanmi-md","display_name":"Oludamilola Aladesanmi MD","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/5e6ceb579581d61ff9a0d36b0fce74899a775ad4d72a95a58d4a9e17cf8d9ac5?s=96&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/139772","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/users\/40613"}],"replies":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=139772"}],"version-history":[{"count":1,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/139772\/revisions"}],"predecessor-version":[{"id":139774,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/posts\/139772\/revisions\/139774"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=\/wp\/v2\/media\/139679"}],"wp:attachment":[{"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=139772"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=139772"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=139772"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/cardiologynownews.org\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=139772"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}