Icosapent Ethyl Effects on Fatty Acid Profiles in Statin-Treated Patients With High Triglycerides: The Randomized, Placebo-controlled ANCHOR Study

Christie M Ballantyne, Mehar S Manku, Harold E Bays, Sephy Philip, Craig Granowitz, Ralph T Doyle Jr, Rebecca A Juliano, Christie M Ballantyne, Mehar S Manku, Harold E Bays, Sephy Philip, Craig Granowitz, Ralph T Doyle Jr, Rebecca A Juliano

Abstract

Introduction: Fatty acid content in plasma and red blood cells (RBCs) may provide insight into potential physiologic benefits of omega-3 fatty acids. Icosapent ethyl is a pure prescription form of eicosapentaenoic acid (EPA) ethyl ester approved by the US Food and Drug Administration at a dose of 4 g/day as an adjunct to diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dl) hypertriglyceridemia.

Methods: This was a prespecified exploratory subset analysis of the ANCHOR study, which randomized 702 statin-treated patients at increased cardiovascular risk with triglycerides 200-499 mg/dl and controlled low-density lipoprotein cholesterol (40-99 mg/dl). This analysis examined effects of icosapent ethyl 4 g/day versus placebo on fatty acid levels in plasma and RBCs using a gas chromatograph assay method with flame ionization detector.

Results: In plasma, treatment with icosapent ethyl 4 g/day resulted in significant increases versus placebo in the mean concentrations of EPA (+ 635%; P < 0.0001) and its metabolite, docosapentaenoic acid n-3 (+ 143%; P < 0.0001) with no significant change in docosahexaenoic acid. Treatment with icosapent ethyl 4 g/day versus placebo also resulted in significant decreases in the omega-6 fatty acids linoleic acid (- 25%) and arachidonic acid (AA; - 31%), as well as the AA/EPA ratio (- 91%). Icosapent ethyl 4 g/day also decreased the omega-9 fatty acid oleic acid (- 29%) and the saturated fatty acids palmitic acid (- 23%) and stearic acid (- 16%) (all P < 0.0001). Results were similar for RBCs.

Conclusions: Icosapent ethyl 4 g/day significantly increased EPA and produced other potentially beneficial shifts in fatty acids in plasma and RBCs versus placebo.

Trial registration: ClinicalTrials.gov Identifier, NCT01047501 FUNDING: Amarin Pharma Inc. Plain language summary available for this article.

Keywords: Arachidonic acid; Eicosapentaenoic acid; Fatty acids; Hypertriglyceridemia; Icosapent ethyl; Omega-3 fatty acids; Omega-6 fatty acids.

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