Prescription omega-3 fatty acid products containing highly purified eicosapentaenoic acid (EPA)

Abstract

The omega-3 fatty acid eicosapentaenoic acid (EPA) has multiple actions potentially conferring cardiovascular benefit, including lowering serum triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) levels and potentially reducing key steps in atherogenesis. Dietary supplements are a common source of omega-3 fatty acids in the US, but virtually all contain docosahexaenoic acid (DHA) in addition to EPA, and lipid effects differ between DHA and EPA. Contrary to popular belief, no over-the-counter omega-3 products are available in the US, only prescription products and dietary supplements. Among the US prescription omega-3 products, only one contains EPA exclusively (Vascepa); another closely related prescription omega-3 product also contains highly purified EPA, but is approved only in Japan and is provided in different capsule sizes. These high-purity EPA products do not raise low-density lipoprotein cholesterol (LDL-C) levels, even in patients with TG levels >500 mg/dL, in contrast to the increase in LDL-C levels with prescription omega-3 products that also contain DHA. The Japanese prescription EPA product was shown to significantly reduce major coronary events in hypercholesterolemic patients when added to statin therapy in the Japan EPA Lipid Intervention Study (JELIS). The effects of Vascepa on cardiovascular outcomes are being investigated in statin-treated patients with high TG levels in the Reduction of Cardiovascular Events With EPA-Intervention Trial (REDUCE-IT).

Keywords: Cardiovascular disease; Cholesterol; Drug therapy; Eicosapentaenoic acid; Ethyl icosapentate; Hypertriglyceridemia; Icosapent ethyl; Inflammation; Omega-3 fatty acids; Triglycerides.

Fig. 1

Effect of Vascepa on lipid levels in patients with very high TG levels (≥500 and ≤2000 mg/dL) in the MARINE study. Shown are the median changes from baseline to week 12 in the intent-to-treat population [7]. HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; MARINE, Multi-center, Placebo-controlled, Randomized, Double-blind, 12-week Study with an Open-label Extension; Non-HDL-C, non-high-density lipoprotein cholesterol; TG, triglyceride; Total C, total cholesterol

Fig. 2

Effect of Vascepa on lipid levels in patients with high TG levels (≥200 and <500 mg/dL) despite LDL-C control while on statin therapy in the ANCHOR study. Shown are the median changes from baseline to week 12 in the intent-to-treat population [8]. HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Non-HDL-C, non-high-density lipoprotein cholesterol; TG, triglyceride; Total C, total cholesterol

Fig. 3

Mean trough total EPA concentrations (±SD) in plasma at baseline and at EOT in Vascepa and Epadel studies [98]. The PK study examined Vascepa in healthy adult subjects [101]. MARINE evaluated Vascepa in patients with very high TG levels (≥500 and ≤2000 mg/dL) [7]. ANCHOR evaluated Vascepa in patients with high TG levels (≥200 and <500 mg/dL) despite LDL-C control while on statin therapy [8]. Finally, JELIS evaluated Epadel in Japanese patients with hypercholesterolemia (total cholesterol ≥250 mg/dL) with or without CAD [36]. EOT = 4 weeks for the phase 1 PK study and 12 weeks in the MARINE and ANCHOR studies. JELIS was an outcome study with a planned follow-up of 5 years. Baseline values were not subtracted from EOT values. CAD, coronary artery disease; EOT, end of treatment; EPA, eicosapentaenoic acid; JELIS, Japan EPA Lipid Intervention Study; LDL-C, low-density lipoprotein cholesterol; MARINE, Multi-center, Placebo-controlled, Randomized, Double-blind, 12-week Study with an Open-label Extension; PK, pharmacokinetic; SD, standard deviation; TG, triglyceride