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.