Skip to main content
Top
Published in: American Journal of Cardiovascular Drugs 6/2014

01-12-2014 | Adis Drug Evaluation

Icosapent Ethyl: A Review of Its Use in Severe Hypertriglyceridemia

Authors: Esther S. Kim, Paul L. McCormack

Published in: American Journal of Cardiovascular Drugs | Issue 6/2014

Login to get access

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.
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference 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. 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.
4.
go back to reference Jacobson TA. Perspectives on a new prescription omega-3 fatty acid, icosapent ethyl, for hypertriglyceridemia. Clin Lipidol. 2014;9(2):149–61.CrossRef Jacobson TA. Perspectives on a new prescription omega-3 fatty acid, icosapent ethyl, for hypertriglyceridemia. Clin Lipidol. 2014;9(2):149–61.CrossRef
5.
go back to reference 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. 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.
6.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
7.
go back to reference Bradberry JC, Hilleman DE. Overview of omega-3 fatty acid therapies. PT. 2013;38(11):681–91. Bradberry JC, Hilleman DE. Overview of omega-3 fatty acid therapies. PT. 2013;38(11):681–91.
8.
go back to reference Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626–35.PubMedCrossRef Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626–35.PubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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.PubMed 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.PubMed
17.
go back to reference Harris WS, Bulchandani D. Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol. 2006;17(4):387–93.PubMedCrossRef Harris WS, Bulchandani D. Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol. 2006;17(4):387–93.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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. 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.
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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. 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.
23.
go back to reference Weintraub HS. Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014;126(7):7–18.PubMedCrossRef Weintraub HS. Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014;126(7):7–18.PubMedCrossRef
24.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
25.
go back to reference 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.CrossRef 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.CrossRef
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference 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.CrossRef 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.CrossRef
29.
go back to reference 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 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.
30.
go back to reference 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.CrossRef 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.CrossRef
31.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
36.
go back to reference 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 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.
Metadata
Title
Icosapent Ethyl: A Review of Its Use in Severe Hypertriglyceridemia
Authors
Esther S. Kim
Paul L. McCormack
Publication date
01-12-2014
Publisher
Springer International Publishing
Published in
American Journal of Cardiovascular Drugs / Issue 6/2014
Print ISSN: 1175-3277
Electronic ISSN: 1179-187X
DOI
https://doi.org/10.1007/s40256-014-0099-7

Other articles of this Issue 6/2014

American Journal of Cardiovascular Drugs 6/2014 Go to the issue

Acknowledgement to Referees

Acknowledgement to Referees