Icosapent Ethyl, a Pure Ethyl Ester of Eicosapentaenoic Acid: Effects on Circulating Markers of Inflammation from the MARINE and ANCHOR Studies
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BACKGROUND: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved by the US Food and Drug Administration as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. In addition to TG-lowering effects, IPE also reduces non-high-density lipoprotein cholesterol and apolipoprotein B levels without significantly increasing low-density lipoprotein cholesterol (LDL-C) in patients with very high TG levels ≥500 mg/dL (MARINE study) and in patients with well-controlled LDL-C and residually high TG levels 200-500 mg/dL (ANCHOR study). This analysis examined the effect of IPE on inflammatory markers in patients from MARINE and ANCHOR. METHODS: MARINE (N = 229) and ANCHOR (N = 702) were Phase III, double-blind studies that randomized hypertriglyceridemic patients to IPE 4 g/day, 2 g/day, or placebo. This analysis assessed the median placebo-adjusted percentage change from baseline in markers representing various stages of atherosclerotic inflammation such as intercellular adhesion molecule-1 (ICAM-1), oxidized low-density lipoprotein (Ox-LDL), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP). RESULTS: Compared to placebo, IPE 4 g/day significantly decreased Ox-LDL (13 %, p < 0.0001, ANCHOR), Lp-PLA(2) (14 %, p < 0.001, MARINE; 19 %, p < 0.0001, ANCHOR), and hsCRP levels (36 %, p < 0.01, MARINE; 22 %, p < 0.001, ANCHOR), but did not significantly change ICAM-1 and IL-6 levels. In the MARINE study, IPE 2 g/day did not significantly change ICAM-1, Ox-LDL, Lp-PLA(2), IL-6, or hsCRP levels. Also, compared to placebo in the ANCHOR study, IPE 2 g/day significantly decreased Lp-PLA(2) levels (8 %, p < 0.0001), but did not significantly change levels of other assessed inflammatory markers. CONCLUSION: Compared to placebo, in hypertriglyceridemic patients, IPE 4 g/day significantly decreased Ox-LDL, Lp-PLA(2), and hsCRP levels.
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Some clinical studies with higher-dose EPA suggest beneficial effects on markers of oxidation and inflammation, coronary plaque characteristics, and major CV events.
“In addition to beneficial changes to TG‐rich lipoproteins and other plasma lipid markers, some clinical studies with higher‐dose EPA also suggest beneficial effects on markers of oxidation and inflammation, coronary plaque characteristics, and major CV events.16, 25, 26, 29, 31, 32, 33”
From Rationale and design of <scp>REDUCE‐IT</scp> : Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (2017) · cites this paper as [29]
The Conclusion (page unavailable) reports that 4 g/day of icosapent ethyl significantly reduced oxidized LDL and inflammatory markers, supporting that part of the claim. The Discussion (page unavailable) says MARINE and ANCHOR were not designed or large enough to assess cardiovascular outcomes; the paper does not report beneficial changes in coronary plaque characteristics or major cardiovascular events. (LLM, conf=0.88)
Experimental — accuracy not yet measuredStudies administering higher-dose EPA suggest additional beneficial effects beyond lipid-lowering that may be unique to EPA relative to other TG-lowering therapies, such as beneficial changes in coronary plaque characteristics, which may lead to reductions in major CV events.
“Finally, studies administering higher‐dose EPA suggest additional beneficial effects beyond lipid‐lowering that may be unique to EPA relative to other TG‐lowering therapies, such as beneficial changes in coronary plaque characteristics, which may lead to reductions in major CV events.4, 16, 25, 26, 27, 28, 29, 30, 31, 32, 33”
From Rationale and design of <scp>REDUCE‐IT</scp> : Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (2017) · cites this paper as [29]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIcosapent ethyl is a highly purified ethyl ester of EPA that improves atherogenic dyslipidemia by reducing TG, TG-rich lipoproteins, and factors involved in their metabolism, without raising LDL-C.
“Icosapent ethyl (Vascepa; Amarin Pharma Inc., Bedminster, NJ) is a highly purified ethyl ester of EPA, which has been reported to improve atherogenic dyslipidemia characterized by reductions in TG, TG‐rich lipoproteins, and factors involved in their metabolism, without raising LDL‐C.25, 26, 27, 28, 29”
From Rationale and design of <scp>REDUCE‐IT</scp> : Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (2017) · cites this paper as [29]
Recent EPA ethyl ester studies reported a placebo-corrected decrease in high-sensitivity C-reactive protein.
“Although recent investigations of EPA-EE have reported a placebo-corrected reduction on hs-CRP, 23,26,55”
From Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: The EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial (2014) · cites this paper as [55]
EPA has additional effects on lipoproteins and atherosclerotic plaque that may contribute to its antiatherogenic properties.
“EPA exerts additional effects on lipoproteins and atherosclerotic plaque, which may contribute to its antiatherogenic properties”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [51]
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- Authors
- Bays, H. E., Ballantyne, C. M., Braeckman, R. A., Stirtan, W. G., & Soni, P. N.
- Affiliations
- Louisville Metabolic and Atherosclerosis Research Center (US)
- Baylor College of Medicine (US)
- Amarin (United States) (US)
- Corresponding author
- Bays, Harold E.
- Venue
- American Journal of Cardiovascular Drugs
- Published
- 2013-01-17
- Volume
- 13
- Issue
- 1
- Pages
- 37-46
- ISSN
- 1175-3277 (ISSN-L)
- 1179-187X
- PMC
- PMC3572383
- OpenAlex
- W2091743718
- Cited by
- 141
- References
- 34
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 13 · 2021: 11 · 2020: 25 · 2019: 16 · 2018: 10 · 2017: 8 · 2016: 11 · 2015: 8 · 2014: 7 · 2013: 3
- FWCI
- 8.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- American Journal of Cardiovascular Drugs (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- American Heart Association
- Abbott Laboratories
- Amgen
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Medpace
- Alere
- Amarin Corporation
- Kowa Company
- Eisai
- Shionogi
- Esperion Therapeutics
- National Institutes of Health
- Genentech
- Amarin Pharma
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- icosapent ethyl, eicosapentaenoic acid ethyl ester, hypertriglyceridemia, atherosclerotic inflammation, inflammatory markers, oxidized LDL, lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, interleukin-6, ICAM-1
- MeSH terms
- Adult, Aged, Double-Blind Method, Esters, Female, Follow-Up Studies, Humans, Inflammation, Male, Middle Aged, Eicosapentaenoic Acid, Hypertriglyceridemia, Biomarkers, Treatment Outcome, Inflammation Mediators
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