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Cited by 201Fatty Acid Research and HealthLipid metabolism and disordersLipoproteins and Cardiovascular Health

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The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia

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Backes, James, Anzalone, Deborah, Hilleman, Daniel, Catini, Julia·2016·Lipids in Health and Disease
DOI 10.1186/s12944-016-0286-4PMC PMC4957330
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Abstract

Hypertriglyceridemia (triglycerides > 150 mg/dL) affects ~25 % of the United States (US) population and is associated with increased cardiovascular risk. Severe hypertriglyceridemia (≥ 500 mg/dL) is also a risk factor for pancreatitis. Three omega-3 fatty acid (OM3FA) prescription formulations are approved in the US for the treatment of adults with severe hypertriglyceridemia: (1) OM3FA ethyl esters (OM3EE), a mixture of OM3FA ethyl esters, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Lovaza®, Omtryg™, and generics); (2) icosapent ethyl (IPE), EPA ethyl esters (Vascepa®); and (3) omega-3 carboxylic acids (OM3CA), a mixture of OM3FAs in free fatty acid form, primarily EPA, DHA, and docosapentaenoic acid (Epanova®). At approved doses, all formulations substantially reduce triglyceride and very-low-density lipoprotein levels. DHA-containing formulations may also increase low-density lipoprotein cholesterol. However, this is not accompanied by increased non-high-density lipoprotein cholesterol, which is thought to provide a better indication of cardiovascular risk in this patient population. Proposed mechanisms of action of OM3FAs include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation. OM3CA bioavailability (area under the plasma concentration-time curve from zero to the last measurable concentration) is up to 4-fold greater than that of OM3FA ethyl esters, and unlike ethyl esters, the absorption of OM3CA is not dependent on pancreatic lipase hydrolysis. All three formulations are well tolerated (the most common adverse events are gastrointestinal) and demonstrate a lack of drug-drug interactions with other lipid-lowering drugs, such as statins and fibrates. OM3FAs appear to be an effective treatment option for patients with severe hypertriglyceridemia.

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Crossref · 10.1186/s12944-016-0286-4

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Fig. 1 Proposed mechanisms of action of prescription formulations of long-chain omega-3 fatty acids. ApoCIII apolipoprotein CIII, Acetyl Co-A acetyl coenzyme A, DGAT diglyceride acyltransferase; FA fatty acid, LPL lipoprotein lipase, TG triglyceride, VLDL very-low-density lipoprotein
Fig. 1 Proposed mechanisms of action of prescription formulations of long-chain omega-3 fatty acids. ApoCIII apolipoprotein CIII, Acetyl Co-A acetyl coenzyme A, DGAT diglyceride acyltransferase; FA fatty acid, LPL lipoprotein lipase, TG triglyceride, VLDL very-low-density lipoproteinCC BY · PubMed Central
Fig. 2 TG reduction observed with varying doses of omega-3 carboxylic acids, omega-3 ethyl esters, and icosapent ethyl in (a) patients with severe hypertriglyceridemia (TG ≥ 500 mg/dL) [14, 16, 17] and (b) statin-treated patients with high baseline TG levels (TG level ≥ 200 mg/dL and < 500 mg/dL) [20, 21, 24] Data not available for OM3EE at 2 g/day. OM3CA = Percentage change from baseline expressed as least-squares geometric mean; OM3EE = percentage change from baseline expressed as geometric mean; IPE = percentage change from baseline expressed as median. †Placebo used = olive oil; ‡Placebo used = vegetable oil; §Placebo used = mineral oil; ǁPlacebo used = corn oil; ¶Placebo not specified. IPE icosapent ethyl, OM3CA omega-3 carboxylic acids, OM3EE omega-3 ethyl esters, TG triglyceride
Fig. 2 TG reduction observed with varying doses of omega-3 carboxylic acids, omega-3 ethyl esters, and icosapent ethyl in (a) patients with severe hypertriglyceridemia (TG ≥ 500 mg/dL) [14, 16, 17] and (b) statin-treated patients with high baseline TG levels (TG level ≥ 200 mg/dL and < 500 mg/dL) [20, 21, 24] Data not available for OM3EE at 2 g/day. OM3CA = Percentage change from baseline expressed as least-squares geometric mean; OM3EE = percentage change from baseline expressed as geometric mean; IPE = percentage change from baseline expressed as median. †Placebo used = olive oil; ‡Placebo used = vegetable oil; §Placebo used = mineral oil; ǁPlacebo used = corn oil; ¶Placebo not specified. IPE icosapent ethyl, OM3CA omega-3 carboxylic acids, OM3EE omega-3 ethyl esters, TG triglycerideCC BY · PubMed Central

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Metadata

Authors
Backes, J., Anzalone, D., Hilleman, D., & Catini, J.
Affiliations
  • University of Kansas (US)
  • AstraZeneca (United States) (US)
  • Creighton University (US)
Corresponding author
Backes, James
ORCID
Venue
Lipids in Health and Disease
Publisher
Springer Science and Business Media LLC
Published
2016-07-22
Volume
15
Issue
1
Pages
118-118
ISSN
1476-511X (ISSN-L)
DOI
10.1186/s12944-016-0286-4
PMC
PMC4957330
OpenAlex
W2487890137
Cited by
195
References
97
Citations by year
2026: 8 · 2025: 20 · 2024: 20 · 2023: 20 · 2022: 26 · 2021: 29 · 2020: 25 · 2019: 15 · 2018: 9 · 2017: 20 · 2016: 1
FWCI
2.01
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Lipids in Health and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Creighton Digital Repository (CDR) (submittedVersion)
  • KU ScholarWorks (The University of Kansas) (submittedVersion, cc-by)
Funders
AstraZeneca
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Keywords
omega-3 fatty acids, severe hypertriglyceridemia, triglyceride-lowering therapy, icosapent ethyl, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, VLDL, non-HDL cholesterol, lipoprotein lipase, hepatic lipogenesis, fatty acid beta-oxidation, bioavailability, drug-drug interactions, cardiovascular risk, pancreatitis
MeSH terms
Adult, Hypolipidemic Agents, Biological Availability, Docosahexaenoic Acids, Drug Combinations, Esters, Humans, Lipoprotein Lipase, Cholesterol, LDL, Lipoproteins, VLDL, Liver, Oxidation-Reduction, Triglycerides, Eicosapentaenoic Acid, Hypertriglyceridemia, Fatty Acids, Omega-3, Lipogenesis, Diacylglycerol O-Acyltransferase

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