Abstract
Icosapent ethyl (Vascepa®) is a high-purity ethyl ester of eicosapentaenoic acid (EPA) that is de-esterified to EPA following oral administration. Both EPA and docosahexaenoic acid (DHA) are long-chain omega-3 fatty acids that have been associated with triglyceride (TG)-lowering. However, DHA has been associated with increased low-density lipoprotein cholesterol (LDL-C) levels. Icosapent ethyl contains ≥96 % of the EPA ethyl ester, does not contain DHA, and is approved in the USA for use as an adjunct to diet to lower TG levels in adult patients with severe (≥500 mg/dL [≥5.65 mmol/L]) hypertriglyceridemia. In a pivotal phase III trial, oral icosapent ethyl 4 g/day significantly decreased the placebo-corrected median TG levels by 33.1 %. It did not increase LDL-C, had favorable effects on other lipid parameters, and had a tolerability profile similar to that of placebo. Therefore, icosapent ethyl is an effective and well-tolerated agent for the treatment of severe hypertriglyceridemia in adults.
Similar content being viewed by others
References
Jacobson TA, Glickstein SB, Rowe JD, et al. Effects of eicosapentaenoic acid and docosahexaenoic acid on low-density lipoprotein cholesterol and other lipids: a review. J Clin Lipidol. 2012;6(1):5–18.
Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–333.
Murad MH, Hazem A, Coto-Yglesias F, et al. The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis. BMC Endocr Disord. 2012. doi:10.1186/1472-6823-12-2.
Jacobson TA. Perspectives on a new prescription omega-3 fatty acid, icosapent ethyl, for hypertriglyceridemia. Clin Lipidol. 2014;9(2):149–61.
American Heart Association. Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report. Circulation. 2002;106(25):3143–421.
Berglund L, Brunzell JD, Goldberg AC, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969–89.
Bradberry JC, Hilleman DE. Overview of omega-3 fatty acid therapies. PT. 2013;38(11):681–91.
Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626–35.
Saito Y, Yokoyama M, Origasa H, et al. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200(1):135–40.
Guyton JR, Slee AE, Anderson T, et al. Relationship of lipoproteins to cardiovascular events: the AIM-HIGH trial (Atherothrombosis intervention in metabolic syndrome with low HDL/high triglycerides and impact on global health outcomes). J Am Coll Cardiol. 2013;62(17):1580–4.
The HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12.
Mozaffarian D, Wu JH. (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary? J Nutr. 2012;142(3):614S–25S.
Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol. 2011;108(5):682–90.
US FDA. Vascepa (icosapent ethyl) capsules: US prescribing information. 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202057s009lbl.pdf. Accessed 14 Nov 2014.
Braeckman RA, Stirtan WG, Soni PN. Phase 1 study of the effect of icosapent ethyl on warfarin pharmacokinetic and anticoagulation parameters. Clin Drug Investig. 2014;34(7):449–56.
Rustan AC, Nossen JØ, Christiansen EN, et al. Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase. J Lipid Res. 1988;29(11):1417–26.
Harris WS, Bulchandani D. Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol. 2006;17(4):387–93.
Ishida T, Ohta M, Nakakuki M, et al. Distinct regulation of plasma LDL cholesterol by eicosapentaenoic acid and docosahexaenoic acid in high fat diet-fed hamsters: participation of cholesterol ester transfer protein and LDL receptor. Prostaglandins Leukot Essent Fatty Acids. 2013;88(4):281–8.
Bays HE, Braeckman RA, Ballantyne CM, et al. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). J Clin Lipidol. 2012;6(6):565–72.
Ballantyne CM, Bays H, Braeckman R, et al. Icosapent ethyl (eicosapentaenoic acid ethyl ester): effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies [abstract no. 16803 plus poster]. In: AHA Scientific Sessions; 2014; Chicago, IL.
Braeckman RA, Manku MS, Bays HE, et al. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on plasma and red blood cell fatty acids in patients with very high triglyceride levels (results from the MARINE study). Prostaglandins Leukot Essent Fatty Acids. 2013;89(4):195–201.
Braeckman RA, Bays HE, Ballantyne CM, et al. Pharmacokinetic and triglyceride-lowering pharmacodynamic effects of icosapent ethyl (eicosapentaenoic acid ethyl ester) across clinical studies [abstract no. 19343 (plus poster 2016)]. In: 86th Annual Scientific Sessions of the American Heart Association; Nov 19 2013; Dallas, TX.
Weintraub HS. Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014;126(7):7–18.
Bays HE, Ballantyne CM, Braeckman RA, et al. Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. Am J Cardiovasc Drugs. 2013;13(1):37–46.
Ballantyne CM, Bays HE, Braeckman RA, et al. Icosapent ethyl (eicosapentaenoic acid ethyl ester): effects on apolipoprotein C-III in patients from the MARINE and ANCHOR studies [abstract no. 122 plus poster]. J Clin Lipidol. 2014;8(3):313–4.
Braeckman RA, Stirtan WG, Soni PN. Pharmacokinetics of eicosapentaenoic acid in plasma and red blood cells after multiple oral dosing with icosapent ethyl in healthy subjects. CPDD. 2014;3(2):101–8.
Arnold C, Konkel A, Fischer R, et al. Cytochrome P450-dependent metabolism of omega-6 and omega-3 long-chain polyunsaturated fatty acids. Pharmacol Rep. 2010;62(3):536–47.
Braeckman R, Soni P, Stirtan W. Phase 1 study of the effect of icosapent ethyl on atorvastatin pharmacokinetics in healthy subjects [abstract no. 156]. J Clin Lipidol. 2013;7(3):269–70.
Braeckman R, Stirtan W, Soni P. Effects of icosapent ethyl (eicosapentaenoic acid ethyl ester) on pharmacokinetic parameters of rosiglitazone in healthy subjects [abstract no. T-755-P]. In: Annual Obesity Week meeting; Nov 11–16 2013, Atlanta, GA.
Braeckman RA, Stirtan WG, Soni PN. Effect of icosapent ethyl (eicosapentaenoic acid ethyl ester) on omeprazole plasma pharmacokinetics in healthy adults. Drugs RD. 2014;14(3):159–64.
Ballantyne CM, Bays HE, Kastelein JJ, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110(7):984–92.
US FDA. Lovaza (omega-3-acid ethyl esters) capsules: US prescribing information. 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021654s041lbl.pdf. Accessed 14 Nov 2014.
US FDA. Epanova (omega-3-carboxylic acids) capsules: US prescribing information. 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205060s000lbl.pdf. Accessed 14 Nov 2014.
US FDA. Omtryg (omega-3-acid ethyl esters A) capsules: US prescribing information. 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204977s000lbl.pdf. Accessed 14 Nov 2014.
US National Library of Medicine. Omega-3-acid ethyl esters capsules: US prescribing information. 2014. http://dailymed.nlm.nih.gov/dailymed/getFile.cfm?setid=2423ae12-e70e-40db-bf9b-b7597a911413&type=pdf&name=2423ae12-e70e-40db-bf9b-b7597a911413. Accessed 14 Nov 2014.
Amarin Pharma Inc. A study of AMR101 to evaluate its ability to reduce cardiovascular events in high risk patients with hypertriglyceridemia and on statin. The primary objective is to evaluate the effect of 4 g/day AMR101 for preventing the occurrence of a first major cardiovascular event (REDUCE-IT) [ClinicalTrials.gov Identifier NCT01492361] US National Institutes of Health, ClinicalTrials.gov. 2013. http://clinicaltrials.gov/ct2/show/NCT01492361. Accessed 16 July 2014.
Amarin Corporation. Amarin reaffirms its mission to improve patient care with commitment to completing REDUCE-IT cardiovascular outcomes study. 2014. http://investor.amarincorp.com/releasedetail.cfm?ReleaseID=870953. Accessed 22 Sept 2014.
Disclosure
The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the authors on the basis of scientific and editorial merit. Esther S. Kim and Paul L. McCormack are salaried employees of Adis/Springer.
Author information
Authors and Affiliations
Corresponding author
Additional information
The manuscript was reviewed by: J. C. Bradberry, School of Pharmacy and Health Professions, Creighton University, Omaha, NE, USA; D. C. F. Chan, Medicine and Pharmacology RPH Unit, The University of Western Australia, Crawley, WA, Australia; A. Sethi, Department of Medicine, Rosalind Franklin University of Medicine and Sciences, North Chicago, IL, USA.
Rights and permissions
About this article
Cite this article
Kim, E.S., McCormack, P.L. Icosapent Ethyl: A Review of Its Use in Severe Hypertriglyceridemia. Am J Cardiovasc Drugs 14, 471–478 (2014). https://doi.org/10.1007/s40256-014-0099-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40256-014-0099-7