Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies
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Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs.
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Icosapent ethyl 4 g/d for 12 weeks in a high-risk population similar to REDUCE-IT with persistent TG elevation after statins resulted in significant reductions in TG and atherogenic lipoproteins, and achieved plasma EPA levels comparable to the 1.8 g/d dosing group in JELIS.
“Icosapent ethyl 12‐week dosing at 4 g/d in a high‐risk population similar to that within the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE‐IT) who had persistent elevations of TG after treatment with statins resulted in significant reductions in TG and atherogenic lipoproteins,26, 27, 28 as well as comparable plasma EPA levels as the 1.8 g/d dosing group in JEL”
From Rationale and design of <scp>REDUCE‐IT</scp> : Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (2017) · cites this paper as [34]
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Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
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<p>Spotlight on Icosapent Ethyl for Cardiovascular Risk Reduction: Evidence to Date</p>
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- Authors
- Bays, H. E., Ballantyne, C. M., Doyle, R. T., Juliano, R. A., & Philip, S.
- Affiliations
- Louisville Metabolic and Atherosclerosis Research Center (US)
- Houston Methodist (US)
- Amarin (United States) (US)
- Corresponding author
- Bays, Harold E.
- Venue
- Prostaglandins & Other Lipid Mediators
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 125
- Pages
- 57-64
- ISSN
- 1098-8823 (ISSN-L)
- OpenAlex
- W2472970460
- Cited by
- 43
- References
- 11
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 1
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Prostaglandins & Other Lipid Mediators (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Amarin Pharma
- 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 › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- icosapent ethyl, eicosapentaenoic acid, hypertriglyceridemia, triglyceride lowering, nonlinear pharmacokinetics, omega-3 fatty acids, ANCHOR trial, pharmacodynamics
- MeSH terms
- Adult, Hypolipidemic Agents, Clinical Trials as Topic, Dose-Response Relationship, Drug, Erythrocytes, Female, Humans, Male, Middle Aged, Triglycerides, Eicosapentaenoic Acid
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