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Review
. 2025 Jul 12.
doi: 10.1007/s40256-025-00748-7. Online ahead of print.

Targeting Triglycerides: The Rise of Apolipoprotein C3 and Angiopoietin-Like Protein 3 Inhibitors

Taha Mansoor  1 , Vijay Nambi  2   3 , Sachin Parikh  4 , Arunima Misra  2 , Mahmoud Ismayl  5 , Claire Sullivan  6 , Laurence Sperling  7 , Salim S Virani  8   9 , Mahmoud Al Rifai  10 , Santhosh K G Koshy  11   12 , Dmitry Abramov  13 , Abdul Mannan Khan Minhas  2
Affiliations
Review

Targeting Triglycerides: The Rise of Apolipoprotein C3 and Angiopoietin-Like Protein 3 Inhibitors

Taha Mansoor et al. Am J Cardiovasc Drugs. .

Abstract

Hypertriglyceridemia has been proposed as a risk factor for atherosclerotic cardiovascular disease (ASCVD). Triglycerides (TG) are viewed as a marker for remnant cholesterol in triglyceride-rich lipoproteins, as this remnant cholesterol has been identified as a causal risk factor for ASCVD. The limited number of effective treatments for elevated TG has fueled the search for novel pharmacotherapy options, and multiple medication classes are being explored. Apolipoprotein C3 (APOC3) and angiopoietin-like protein 3 (ANGPTL3) are among the most promising targets. Several novel agents utilizing these pathways, including olezarsen, plozasiran, and zodasiran, are currently under development for the management of elevated TG, with olezarsen approved in 2024 for the management of familial chylomicronemia syndrome. This comprehensive review provides updated insights into the development of novel hypertriglyceridemia treatments.

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Conflict of interest statement

Declarations. Funding: No funding was used in the preparation of this manuscript. Conflicts of interest: T.M., V.N., S.P., A.M., M.I., C.S., L.S., S.S.V., M.A.R., S.K.G.K., D.A., and A.M.M.K. declare that they have no potential conflicts of interest that might be relevant to the content of this manuscript. The views expressed in this publication are those of the authors and do not necessarily represent those of the Department of Veterans Affairs. Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study. Ethics approval: Not applicable. Code availability: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Author contributions: T.M.: conceptualization, data curation, formal analysis, methodology, project administration, supervision, validation, visualization, writing—original draft, writing—review and editing. V.N.: writing—review and editing. M.I.: writing—review and editing. S.P.: writing—review and editing. A.M.: writing—review and editing. C.S.: writing—review and editing. L.S.: writing—review and editing. S.S.V.: writing—review and editing. M.A.R.: writing—review and editing. S.K.G.K.: writing—review and editing. D.A.: writing—review and editing. A.M.M.K.: writing—review and editing, visualization, conceptualization, and supervision.

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