Icosapent ethyl is a highly purified ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid (EPA). Currently, high-dose icosapent ethyl (4 g/day) is indicated to reduce the risk of cardiovascular events in adult statin-treated patients at high cardiovascular risk with elevated TG (≥ 150 mg/dL or ≥ 1.7 mmol/L) and established cardiovascular disease, or with diabetes and at least one other cardiovascular risk factor (1). This indication is supported by evidence from REDUCE-IT, in which high-dose icosapent ethyl unequivocally contributed to ASCVD event reduction for both first and subsequent cardiovascular events, against a background of well-controlled LDL-C levels on statin therapy (2,3).
The mechanisms contributing to the reduction of cardiovascular events with icosapent ethyl in REDUCE-IT are likely to be multi-factorial (4). These include reduction of TG-rich lipoproteins, anti-inflammatory and antioxidant effects, reduction of macrophage accumulation, improved endothelial function, increased fibrous cap thickness/stability, and antiplatelet effects. There is also evidence to suggest that the biology of EPA differs from docosahexaenoic acid (DHA), specifically in respect of effects on membrane structure, lipid oxidation, inflammatory biomarkers, and endothelial function (4). Such distinct molecular effects may explain the different findings of REDUCE-IT (strongly positive) and STRENGTH which tested an EPA/DHA combination (neutral).
View key references >
1. Summary of Product Characteristics, Vazkepa 998 mg soft capsules.
2. Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22. PUBMED https://pubmed.ncbi.nlm.nih.gov/30415628/
3. Boden WE, Bhatt DL, Toth PP, et al. Profound reductions in first and total cardiovascular events with icosapent ethyl in the REDUCE-IT trial: why these results usher in a new era in dyslipidaemia therapeutics. Eur Heart J 2020;41:2304-12. PUBMED https://pubmed.ncbi.nlm.nih.gov/31872245/
4. Mason RP, Libby P, Bhatt DL. Emerging mechanisms of cardiovascular protection for the omega-3 fatty acid eicosapentaenoic acid. Arterioscler Thromb Vasc Biol 2020;40:1135-114. PUBMED https://pubmed.ncbi.nlm.nih.gov/32212849/
