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Elevated triglyceride levels are associated with increased risk of acute pancreatitis and atherosclerotic cardiovascular disease (ASCVD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>\n                      Conventional triglyceride-lowering therapies, such as fibrates and omega-3 fatty acids, have limited efficacy in reducing triglycerides and in reducing the risk of pancreatitis or ASCVD in patients with severe hypertriglyceridemia. ApoC-III inhibits lipoprotein lipase and impairs clearance of both triglyceride-rich and cholesterol-rich lipoproteins. Novel therapies targeting\n                      <jats:italic>APOC3<\/jats:italic>\n                      mRNA to reduce triglycerides, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), achieve greater triglyceride reductions than standard agents. Volanesorsen and olezarsen, both ASOs, are approved as an adjunct to diet to reduce triglycerides in familial chylomicronemia syndrome (FCS) in different regions. Plozasiran, an siRNA, is in late-stage clinical development. Indirect cross-trial comparisons were performed, aligned by timepoint and outcome measures, and indicate comparable efficacy of olezarsen and plozasiran in patients with chylomicronemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>\n                      <jats:italic>APOC3<\/jats:italic>\n                      inhibition is now an established therapeutic approach for reducing the risk of acute pancreatitis in FCS, with three agents, volanesorsen, olezarsen, and plozasiran, demonstrating efficacy. However, its role in ASCVD prevention remains unproven. This review evaluates current\n                      <jats:italic>APOC3\u2009<\/jats:italic>\n                      \u2013\u2009targeted therapies for FCS, including available comparative data, and synthesizes the emerging literature on the potential of\n                      <jats:italic>APOC3<\/jats:italic>\n                      inhibition to reduce the burden of acute pancreatitis in broader populations with severe hypertriglyceridemia, as well as its potential role in ASCVD risk reduction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11883-025-01345-4","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T08:00:07Z","timestamp":1760342407000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Anti-apoC-III Therapies and Implications for Treatment of Pancreatitis and Cardiovascular Disease"],"prefix":"10.1007","volume":"27","author":[{"given":"Sotirios","family":"Tsimikas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"issue":"15","key":"1345_CR1","doi-asserted-by":"publisher","first-page":"4311","DOI":"10.3390\/jcm11154311","volume":"11","author":"A Nemeth","year":"2022","unstructured":"Nemeth A, Harangi M, Daroczy B, Juhasz L, Paragh G, Fulop P. 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All studies with human subjects are published and followed ethical, institutional standards.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and Animal Rights"}},{"value":"Conflict of Interest: Dr Tsimikas is an employee of Ionis pharmaceuticals and University of California San Diego (UCSD), holds individual stock and options from Ionis, has received grant\/research support paid to UCSD from the National Heart, Lung, and Blood Institute (NHLBI)\/Novartis, is a consultant and receives fees\/honoraria from Novartis, receives royalties from patents held by UCSD, and has ownership interest from Kleanthi and Oxitope Pharma.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"103"}}