Translating plasma eicosapentaenoic acid concentrations into erythrocyte percentages of eicosapentaenoic acid plus docosahexaenoic acid during treatment with icosapent ethyl

J Clin Lipidol. Sep-Oct 2019;13(5):771-777. doi: 10.1016/j.jacl.2019.07.001. Epub 2019 Jul 12.


Background: The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) study demonstrated that 4 g/d of eicosapentaenoic acid (EPA) ethyl esters (icosapent ethyl [IPE]) reduced risk for major cardiovascular events by 25% in statin-treated patients with residual hypertriglyceridemia. How this treatment affected red blood cell (RBC) EPA and docosahexaenoic acid (DHA) levels (ie, the Omega-3 Index [O3I]) was not reported, but effects on plasma EPA concentrations were reported.

Objective: The aim of the study was to estimate baseline and final O3I levels in REDUCE-IT.

Methods: First, deidentified data from our laboratory on RBC and plasma EPA and DHA from 2311 patients with similar lipid profiles as those in REDUCE-IT were used to generate a regression equation, which was then used to estimate the O3I from plasma FA concentrations. Second, previously published data on the effects of IPE on RBC FA concentrations were also converted to the O3I.

Results: Both approaches (from calculations and prior publications) suggested that baseline and follow-up O3I levels were about 5% and 7%, respectively. In addition, plasma EPA levels (but not the O3I) were noted to be influenced by triglyceride levels.

Conclusion: For patients using 4 g of IPE, an estimated O3I value of about 7% reflects a cardioprotective state. Plasma EPA concentrations may be ill-suited as treatment targets because they are confounded by triglyceride levels.

Keywords: Biomarker; Docosahexaenoic acid; Eicosapentaenoic acid; Icosapent ethyl; Omega-3 index.

MeSH terms

  • Docosahexaenoic Acids / blood*
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / blood*
  • Eicosapentaenoic Acid / pharmacology
  • Erythrocyte Membrane / drug effects
  • Erythrocyte Membrane / metabolism
  • Erythrocytes / metabolism*
  • Humans


  • Docosahexaenoic Acids
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid