1. Benjamin, EJ, Muntner, P, Alonso, A, et al. Heart Disease and Stroke Statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.
Google Scholar | Crossref | Medline2. Mokdad, AH, Ballestros, K, Echko, M, et al. The state of US health, 1990-2016: burden of diseases, injuries, and risk factors among US states. JAMA. 2018;319(14):1444–1472.
Google Scholar | Crossref | Medline3. Roth, GA, Johnson, C, Abajobir, A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017;70(1):1–25.
Google Scholar | Crossref | Medline4. Collins, R, Reith, C, Emberson, J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532–2561.
Google Scholar | Crossref | Medline5. Ganda, OP, Bhatt, DL, Mason, RP, Miller, M, Boden, WE. Unmet need for adjunctive dyslipidemia therapy in hypertriglyderidemia management. J Am Coll Cardiol. 2018;72(3):330–343.
Google Scholar | Crossref | Medline6. Toth, PP, Granowitz, C, Hull, M, Liassou, D, Anderson, A, Philip, S. High triglycerides are associated with increased cardiovascular events, medical costs, and resource utilization: a real-world administrative claims analysis of statin-treated patients with high residual cardiovascular risk. J Am Heart Assoc. 2018;7(15):e008740.
Google Scholar | Crossref | Medline7. Kushner, PA, Cobble, ME. Hypertriglyceridemia: the importance of identifying patients at risk. Postgrad Med. 2016;128(8):848–858.
Google Scholar | Crossref | Medline8. Reiner, Z . Hypertriglyceridaemia and risk of coronary artery disease. Nat Rev Cardiol. 2017;14(7):401–411.
Google Scholar | Crossref | Medline | ISI9. Toth, PP, Philip, S, Hull, M, Granowitz, C. Hypertriglyceridemia is associated with an increased risk of peripheral arterial revascularization in high-risk statin-treated patients: a large administrative retrospective analysis. Clin Cardiol. 2019;42(10):908–913.
Google Scholar | Crossref | Medline10. Klempfner, R, Erez, A, Sagit, BZ, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the bezafibrate infarction prevention study and registry. Circ Cardiovasc Qual Outcomes. 2016;9(2):100–108.
Google Scholar | Crossref | Medline11. Fan, W, Philip, S, Granowitz, C, Toth, PP, Wong, ND. Prevalence of US adults with triglycerides ≥ 150 mg/dl: NHANES 2007–2014. Cardiol Ther. 2020;9(1):207–213.
Google Scholar | Crossref | Medline12. Miller, M, Stone, NJ, Ballantyne, C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–2333.
Google Scholar | Crossref | Medline | ISI13. Baum, SJ, Scholz, KP. Rounding the corner on residual risk: implications of REDUCE-IT for omega-3 polyunsaturated fatty acids treatment in secondary prevention of atherosclerotic cardiovascular disease. Clin Cardiol. 2019;42(9):829–838.
Google Scholar | Crossref14. Kohli, P, Mehta, LS, Miedema, MD. Management of elevated triglycerides in the era of icosapent ethyl. Published 2020. Accessed June 10, 2021. https://www.acc.org/latest-in-cardiology/articles/2020/03/02/12/35/management-of-elevated-triglycerides-in-the-era-of-icosapent-ethyl#.Xl5GnsNA41k.twitter
Google Scholar15. Grundy, SM, Stone, NJ, Bailey, AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2019;73(24):e285–e350.
Google Scholar | Crossref | Medline16. Karlson, BW, Palmer, MK, Nicholls, SJ, Lundman, P, Barter, PJ. A VOYAGER meta-analysis of the impact of statin therapy on low-density lipoprotein cholesterol and triglyceride levels in patients with hypertriglyceridemia. Am J Cardiol. 2016;117(9):1444–1448.
Google Scholar | Crossref | Medline | ISI17. Chatterjee, S, Hajra, A, Bandyopadhyay, D, Ghosh, RK, Deedwania, PC. Defining the role of icosapent ethyl in clinical practice. Am J Cardiovasc Drugs. 2020;20(6):517–524.
Google Scholar | Crossref | Medline18. Vascepa [package insert]. Bridgewater, NJ: Amarin Pharma Inc; 2019.
Google Scholar19. Bhatt, DL, Steg, G, Miller, M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22.
Google Scholar | Crossref | Medline20. Calder, PC . Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol. 2013;75(3):645–662.
Google Scholar | Crossref | Medline | ISI21. Sheikh, O, Vande Hei, AG, Battisha, A, Hammad, T, Pham, S, Chilton, R. Cardiovascular, electrophysiologic, and hematologic effects of omega-3 fatty acids beyond reducing hypertriglyceridemia: as it pertains to the recently published REDUCE-IT trial. Cardiovasc Diabetol. 2019;18(1):84.
Google Scholar | Crossref | Medline22. Bhatt, DL, Budoff, MJ, Mason, RP. A revolution in omega-3 fatty acid research. J Am Coll Cardiol. 2020;76(18):2098–2101.
Google Scholar | Crossref | Medline23. Arterburn, LM, Hall, EB, Oken, H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006;83(6 suppl):1467S–1476S.
Google Scholar | Crossref | Medline24. Dixon, DL. Catch of the day: icosapent ethyl for reducing cardiovascular risk. Am J Med. 2020;133(7):802–804.
Google Scholar | Crossref | Medline25. Aung, T, Halsey, J, Kromhout, D, et al. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77917 individuals. JAMA Cardiol. 2018;3(3):225–234.
Google Scholar | Crossref | Medline26. GISSI Prevenzione Investigators . Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo studio Della Sopravvivenza Nell’infarto Miocardico. Lancet. 1999;354(9177):447–455.
Google Scholar | Crossref | Medline27. Rauch, B, Schiele, R, Schneider, S, et al. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation. 2010;122(21):2152–2159.
Google Scholar | Crossref | Medline | ISI28. Kromhout, D, Giltay, EJ, Geleijnse, JM. n-3 Fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015–2026.
Google Scholar | Crossref | Medline | ISI29. ORIGIN Trial Investigators . n-3 Fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367(4):309–318.
Google Scholar | Crossref | Medline30. ASCEND Study Collaborative Group , Bowman, L, Mafham, M, et al. Effects of n-3 fatty acid supplements in diabetes mellitus. N Engl J Med. 2018;379(16):1540–1550.
Google Scholar | Crossref | Medline31. Manson, JE, Cook, NR, Lee, IM, et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380(1):23–32.
Google Scholar | Crossref | Medline32. Nicholls, SJ, Lincoff, AM, Garcia, M, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: The STRENGTH randomized clinical trial. JAMA. 2020;324(22):2268–2280.
Google Scholar | Crossref | Medline33. Kalstad, AA, Myhre, PL, Laake, K, et al. Effects of n-3 fatty acid supplements in elderly patients after myocardial infarction: a randomized controlled trial. Circulation. 2021;143(6):528–539.
Google Scholar | Crossref | Medline34. Yokoyama, M, Origasa, H, Matsuzaki, M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–1098.
Google Scholar | Crossref | Medline | ISI35. 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):135–140.
Google Scholar | Crossref | Medline | ISI36. Bhatt, DL, Steg, PG, Miller, M, et al. Effects of icosapent ethyl on total ischemic events: from REDUCE-IT. J Am Coll Cardiol. 2019;73(22):2791–2802.
Google Scholar | Crossref | Medline37. Bhatt, DL, Miller, M, Brinton, EA, et al. REDUCE-IT USA: results from the 3,146 patients randomized in the United States. Circulation. 2020;141(5):367–375.
Google Scholar | Crossref | Medline38. Weintraub, WS, Bhatt, DL, Zhang, Z, et al. Cost-effectiveness of icosapent ethyl in REDUCE-IT [abstract]. Circulation. 2019;140(25):e969–e970.
Google Scholar | Medline39. Synnott, PG, McQueen, RB, Ollendorf, DA, Campbell, JD, Pearson, SD. The effectiveness and value of rivaroxaban and icosapent ethyl as additive therapies for cardiovascular disease. J Manag Care Spec Pharm. 2020;26(6):782–785.
Google Scholar | Medline40. Peterson, BE, Bhatt, DL, Steg, PG, et al. Reduction in revascularization with icosapent ethyl: insights from REDUCE-IT revascularization analyses. Circulation. 2021;143(1):33–44.
Google Scholar | Crossref | Medline41. Bhatt, DL, Brinton, EA, Miller, M, et al. Icosapent ethyl provides consistent cardiovascular benefit in patients with diabetes in REDUCE-IT [Presentation]. Presented at: Annual Scientific Sessions of the American Diabetes Association; . Chicago, IL.
Google Scholar42. Icosapent ethyl Hikma Generic [package insert]. Eatontown, NJ: Hikma Pharmaceuticals; 2020.
Google Scholar43. UMIN-CTR Clinical Trial . Randomized trial for evaluation in secondary prevention efficacy of combination therapy—statin and eicosapentaenoic acid UMIN000012069. Published 2018. Accessed June 10, 2021. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&recptno=R000014051&type=summary&language=E
Google Scholar44. Patel, PN, Patel, SM, Bhatt, DL. Cardiovascular risk reduction with icosapent ethyl. Curr Opin Cardiol. 2019;34(6):721–727.
Google Scholar | Crossref | Medline45. Kim, ES, McCormack, PL. Icosapent ethyl: a review of its use in severe hypertriglyceridemia. Am J Cardiovasc Drugs. 2014;14(6):471–478.
Google Scholar | Crossref | Medline46. Brinton, EA, Mason, RP. Prescription omega-3 fatty acid products containing highly purified eicosapentaenoic acid (EPA). Lipids Health Dis. 2017;16(1):23.
Google Scholar | Crossref | Medline47. Braeckman, RA, Manku, MS, Bays, HE, Stirtan, WG, Soni, PN. 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.
Google Scholar | Crossref | Medline48. Mason, RP, Sherratt, SCR. Eicosapentaenoic acid inhibits oxidation of very large density lipoproteins (VLDL) in a dose-dependent manner over time as compared to docosahexaenoic acid in vitro [abstract]. J Am Coll Cardiol. 2020;75(11 suppl 1):2238.
Google Scholar | Crossref49. Harris, WS . Understanding why REDUCE-IT was positive—mechanistic overview of eicosapentaenoic acid. Prog Cardiovasc Dis. 2019;62(5):401–405.