Abstract
Omega-3 carboxylic acids (Epanova®) [OM3-CA] is the first free fatty acid form of long-chain marine omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid being the most abundant) to be approved by the US FDA as an adjunct to diet to lower triglyceride levels in patients with severe hypertriglyceridemia (≥500 mg/dL). Oral OM3-CA has greater bioavailability than ethyl ester forms of omega-3 and, unlike omega-3 acid ethyl esters, does not require co-ingestion of a high-fat meal, as it does not need pancreatic enzyme activity for absorption. In the 12-week EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial, OM3-CA 2 or 4 g/day significantly reduced serum triglyceride levels relative to placebo. Other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and very low-density lipoprotein cholesterol (VLDL-C) levels, were also reduced significantly with OM3-CA relative to placebo. Low-density lipoprotein cholesterol levels were increased significantly with OM3-CA relative to placebo; however, these increases were not accompanied by increases in the circulating concentrations of non-HDL-C, VLDL-C, or apolipoprotein B. OM3-CA was generally well tolerated in this study, with most adverse events being of mild or moderate severity. Although additional comparative data are needed to position OM3-CA with respect to other formulations of omega-3 fatty acids, current evidence suggests that OM3-CA is a useful addition to the treatment options available for patients with severe hypertriglyceridemia.
Similar content being viewed by others
References
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.
National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). 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.
World Health Organization. The top 10 causes of death. 2014. http://www.who.int/mediacentre/factsheets/fs310/en/. Accessed 26 Aug 2014.
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.
Kataoka Y, Uno K, Puri R, et al. Epanova and hypertriglyceridemia: pharmacological mechanisms and clinical efficacy. Future Cardiol. 2013;9(2):177–86.
Skulas-Ray AC, West SG, Davidson MH, et al. Omega-3 fatty acid concentrates in the treatment of moderate hypertriglyceridemia. Expert Opin Pharmacother. 2008;9(7):1237–48.
Weintraub H. Update on marine omega-3 fatty acids: management of dyslipidemia and current omega-3 treatment options. Atherosclerosis. 2013;230(2):381–9.
Bradberry JC, Hilleman DE. Overview of omega-3 fatty acid therapies. P T. 2013;38(11):681–91.
Davidson MH. Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol. 2006;98(4A):27i–33i.
GlaxoSmithKline. Lovaza (omega-3 acid ethyl esters) capsules: US prescribing information. 2008. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021654s041lbl.pdf. Accessed 21 Aug 2008.
Trygg Pharma. Omega-3 acid ethyl esters A (Omtryg): US prescribing information. 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/204977s000lbl.pdf. Accessed 21 Aug 2014.
Amarin Corporation. Vascepa (icosapent ethyl) capsules: US prescribing information. 2013. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/202057s009lbl.pdf. Accessed 21 Aug 2014.
AstraZeneca Pharmaceuticals LP. Omega-3 free fatty acids (Epanova): US prescribing information. 2014. http://www1.astrazeneca-us.com/pi/epanova.pdf. Accessed 9 Sep 2014.
Davidson MH, Johnson J, Rooney MW, et al. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: the ECLIPSE (Epanova® compared to Lovaza® in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol. 2012;6(6):573–84.
Offman E, Marenco T, Ferber S, et al. Steady-state bioavailability of prescription omega-3 on a low-fat diet is significantly improved with a free fatty acid formulation compared with an ethyl ester formulation: the ECLIPSE II study. Vasc Health Risk Manag. 2013;9(1):563–73.
Kebir S, Davidson M, Marenco T, et al. Multiple doses of EPA/DHA do not alter the pharmacokinetics of simvastatin or the antiplatelet effect of ASA [abstract no. PII-1]. Clin Pharmacol Ther. 2013;93(Suppl 1):S52–3.
Kastelein JJP, Maki KC, Susekov A, et al. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. J Clin Lipidol. 2014;8(1):94–106.
Kastelein JJP, Maki KC, Susekov A, et al. Management of severe hypertriglyceridemia with a novel omega-3 free-fatty acid formulation: subgroups in the EVOLVE trial [abstract no. 159 plus poster]. J Clin Lipidol. 2013;7(3):271–2.
Rader DJ, Dunbar RL, Maki KC, et al. Apolipoprotein C-III is significantly reduced by prescription omega-3 free fatty acids (Epanova) in patients with severe hypertriglyceridemia and changes correlate with increases in LDL-C: a sub-analysis of the EVOLVE trial [abstract no. 19030]. Circulation. 2012;126(21 Suppl).
Maki KC, Orloff DG, Nicholls SJ et al. A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial). Clin Ther. 2013;35(9):1400-11.e3.
Kris-Etherton PM, Harris WS, Appel LJ. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol. 2003;23(2):151–2.
AstraZeneca. Outcomes study to assess STatin Residual risk reduction with EpaNova in hiGh CV risk patienTs with hypertriglyceridemia (STRENGTH) [ClinicalTrials.gov identifier NCT02104817] US National Institutes of Health, ClinicalTrials.gov. 2014. http://clinicaltrials.gov/show/NCT02104817. Accessed 21 Aug 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. Hannah Blair and Sohita Dhillon are salaried employees of Adis/Springer.
Author information
Authors and Affiliations
Corresponding author
Additional information
The manuscript was reviewed by: L. Berglund, UC Davis CTSC, University of California, Davis, Sacramento, CA, USA; K. C. Maki, Midwest Center for Metabolic & Cardiovascular Research, Clinical Research, Chicago, IL, USA; E. Offman, Celerion, Montreal, QC, Canada.
Rights and permissions
About this article
Cite this article
Blair, H.A., Dhillon, S. Omega-3 Carboxylic Acids (Epanova®): A Review of Its Use in Patients with Severe Hypertriglyceridemia. Am J Cardiovasc Drugs 14, 393–400 (2014). https://doi.org/10.1007/s40256-014-0090-3
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40256-014-0090-3