Review of Cardiometabolic Effects of Prescription Omega-3 Fatty Acids

  • Megan F. Burke
  • Frances M. Burke
  • Daniel E. SofferEmail author
Nonstatin Drugs (E. deGoma, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Nonstatin Drugs


Purpose of Review

Populations with significant dietary fish intake tend to have lower cardiovascular (CV) risk and demonstrable physiologic differences including lower lipid/lipoprotein levels and other direct and indirect effects on the arterial wall and inhibiting factors that promote atherosclerosis. Treatment with high doses of pharmacologic-grade omega-3 fatty acid (n-3FA) supplements achieves significant reductions in triglycerides (TG), non-high-density lipoprotein- (non-HDL-) and TG-rich lipoprotein- (TRL-) cholesterol levels. n-3FA supplements have significant effects on markers of atherosclerosis risk including endothelial function, low-density lipoprotein (LDL) oxidation, cellular and humoral markers of inflammation, hemodynamic factors, and plaque stabilization. This review summarizes the lipid and cardiometabolic effects of prescription-grade n-3FAs and will discuss clinical trials, national/organizational guidelines, and expert opinion on the impact of supplemental n-3FAs on CV health and disease.

Recent Findings

Clinical trial evidence supports use of n-3FAs in individuals with established atherosclerotic cardiovascular disease (ASCVD), but the data either does not support or is lacking for other types of cardiometabolic risk including prevention of stroke, treatment in patients with heart failure, diabetes mellitus and prediabetes, and for primary prevention in the general population.


Despite inconsistent findings to support widespread benefit, there is persistent population-wide enthusiasm for n-3FA as a dietary supplement for its cardiometabolic benefits. Fortunately, there are ongoing clinical trials to assess whether the lipid/lipoprotein benefits may be extended to other at-risk populations and whether lower-dose therapy may provide background benefit for primary prevention of ASCVD.


Dietary supplement Omega-3 FA (n-3FA) Eicosapentaenoic acid (EPA) Docosahexaenoic acid (DHA) Linoleic acid (LA) Alpha-linolenic acid (ALA) Triglycerides (TG) Ethyl ester (EE) Fatty acid (FA) Free FA (FFA) 


Compliance with Ethical Standards

Conflict of Interest

Megan F. Burke and Frances M. Burke declare no conflict of interest.

Dr. Soffer reports that he has participated as a local investigator in pharmaceutical company-sponsored clinical trials that provide program support. He has been an investigator with Akcea, Ionis, Novartis, Pfizer, Regeneron, Sanofi, Amgen, Omthera/Astra Zeneca, Regenex/NIH, and Kowa pharmaceuticals, outside the submitted work. He has also received faculty payment for services as a course director for the National Lipid Association.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047–67. Scholar
  2. 2.
    Harris WS, Dayspring TD, Moran TJ. Omega-3 fatty acids and cardiovascular disease: new developments and applications. Postgrad Med. 2013;125(6):100–13. Scholar
  3. 3.
    U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015–2020 dietary guidelines for Americans. 8th Edition. December 2015. Available at Accessed August 7, 2017.
  4. 4.
    Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's Strategic Impact Goal through 2020 and beyond. Circulation. 2010;121:586–613. Scholar
  5. 5.
    Clark TC, Black LI, Stussman BJ, Barnes PM, Nahin RL. Trends in the use of complementary health approaches among adults: United States, 2002–2012. National Health Statistics reports; no 79. Hyattsville, MD: National Center for Health Statistics. 2015. Available at Accessed August 5, 2017.
  6. 6.
    Backes J, Anzalone D, Hilleman D, Catini J. The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia. Lipids Health Dis. 2016;15:118–29. Scholar
  7. 7.
    Sperling LS, Nelson JR. History and future of omega-3 fatty acids in cardiovascular disease. Curr Med Res Opin. 2016;32:301–11. Scholar
  8. 8.
    •• Siscovick DS, Barringer TA, Fretts AM, JHY W, Lichtenstein AH, Costello RB, et al. Omega-3 polyunsaturated fatty acid (fish oil) supplementation and the prevention of clinical cardiovascular disease: a science advisory from the American Heart Association. Circulation. 2017;135:e876–84. Recent and comprehensive review on use of n-3FA supplementation for CVD prevention. CrossRefGoogle Scholar
  9. 9.
    Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr. 2006;83(suppl):1526S–35S.PubMedGoogle Scholar
  10. 10.
    Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: dietary fatty acids for healthy adults. J Acad Nutr Diet. 2014;114:136–53. Scholar
  11. 11.
    Bowen KJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids and cardiovascular disease: are there benefits? Curr Treat Options Cardiovasc Med. 2016;18:69. Scholar
  12. 12.
    Kris-Etherton PM, Fleming JA. Emerging nutrition science on fatty acids and cardiovascular disease: nutritionists’ perspectives. Adv Nutr. 2015;6:326S–37S. Scholar
  13. 13.
    • Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet. 1971;1:1143–5. Landmark observational trial of the impact of n-3FA on reducing CV risk. CrossRefPubMedGoogle Scholar
  14. 14.
    Dyerberg J, Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet. 1979;2:433–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins, Leukot, Essent Fatty Acids. 2013;89(1):1–8. Scholar
  16. 16.
    •• Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2015;1851:469–84. Excellent review of the ant-inflammatory effects of n-3FAs. CrossRefPubMedGoogle Scholar
  17. 17.
    Fialkow J. Omega-3 fatty acid formulations in cardiovascular disease: dietary supplements are not substitutes for prescription products. Am J Cardiovasc Drugs. 2016;16:229–39. Scholar
  18. 18.
  19. 19.
    Prescribing information for Vascepa. Available at Accessed July 21, 2017.
  20. 20.
    Prescribing information for Omytrg. Available at Accessed July 21, 2017.
  21. 21.
    Prescribing information for Epanova. Available at Accessed July 21, 2017.
  22. 22.
    Weintraub HS. Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014;126:7–18. Scholar
  23. 23.
    Ito MK. A comparative overview of prescription omega-3 fatty acid products. Pharmacy and Therapeutics. 2015;40:826–57.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF. 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. Scholar
  25. 25.
    Raposo HF, Patricio PR, Simoes MC, Oliveira HC. Fibrates and fish oil, but not corn oil, up-regulate the expression of the cholesterol ester transfer protein (CETP) gene. J Nutr Biochem. 2014;25(6):669–74. Scholar
  26. 26.
    Graversen CB, Lundbye-Christensen S, Thomsen B, Christensen JH, Schmidt EB. Marine n-3 polyunsaturated fatty acids lower plasma proprotein convertase subtilisin kexin type 9 in pre- and postmenopausal women: a randomised study. Vasc Pharmacol. 2016;76:37–41. Scholar
  27. 27.
    • Karalis DG. A review of clinical practice guidelines for the management of hypertriglyceridemia: a focus on high dose omega-3 fatty acids. Adv Ther. 2017;34:300–23. Excellent review on the management of hypertriglyceridemia. CrossRefPubMedGoogle Scholar
  28. 28.
    Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997;4:385–91.CrossRefPubMedGoogle Scholar
  29. 29.
    Pownall HJ, Brauchi D, Kilinc C, Osmundsen K, Pao Q, Payton-Ross C, et al. Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins. Atherosclerosis. 1999;143(2):285–97. Scholar
  30. 30.
    Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29(7):1354–67. Scholar
  31. 31.
    Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. 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;108:682–90. Scholar
  32. 32.
    Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, 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;110:984–92. Scholar
  33. 33.
    Kastelein JJ, Maki KC, Susekov A, Ezhov M, Nordestgaard BG, Machielse BN, 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;8:94–106. Scholar
  34. 34.
    Maki KC, Orloff DG, Nicholls SJ, Dunbar RL, Roth EM, Curcio D, 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;35:1400–11. Scholar
  35. 35.
    Jacobson TA, Glickstein SB, Rowe JD, Soni PN. 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. Scholar
  36. 36.
    Robinson JG, Stone NJ. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids. Am J Cardiol. 2006;98(suppl):39i–49i. Scholar
  37. 37.
    Nestel PJ, Shige H, Pomeroy SE, Cehun M, Abbey M, Raederstorff D. The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr. 2002;76:326–30.PubMedGoogle Scholar
  38. 38.
    Nestel PJ, Pomeroy SE, Sasahara T, Yamashita T, Liang YL, Dart AM, et al. Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vasc Biol. 1997;17:1163–70.CrossRefPubMedGoogle Scholar
  39. 39.
    Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. Atherosclerosis. 2015;242:357–66. Scholar
  40. 40.
    Bays HE, Ballantyne CM, Braeckman RA, Stirtan WG, Soni PN. 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. Scholar
  41. 41.
    Mason RP, Jacob RF. Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism. Biochim Biophys Acta. 2015;1848:502–9. Scholar
  42. 42.
    Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systemic review. Atherosclerosis. 2006;189:19–30. Scholar
  43. 43.
    Pischon T, Hankinson SE, Hotamisligil GS, Rifai N, Willet WC, Rimm EB. Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women. Circulation. 2003;108:155–60. Scholar
  44. 44.
    Geelen A, Brouwer IA, Schouten EG, Kluft C, Katan MB, Zock PL. Intake of n-3 fatty acids from fish does not lower serum concentrations of C-reactive protein in healthy subjects. Eur J Clin Nutr. 2004;58:1440–2. Scholar
  45. 45.
    Madsen T, Christensen JH, Blom M, Schmidt EB. The effect of dietary n-3 fatty acids on serum concentrations of C-reactive protein: a dose-response study. Br J Nutr. 2003;89:517–22. Scholar
  46. 46.
    Micallef MA, Munro IA, Garg ML. An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur J Clin Nutr. 2009;63:1154–6. Scholar
  47. 47.
    Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med. 1989;320:265–71.CrossRefPubMedGoogle Scholar
  48. 48.
    Lee TH, Hoover RL, Williams JD, et al. Effects of dietary enrichment with eicosapentaenoic acid and docosahexaenoic acid on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med. 1985;312:1217–24.CrossRefPubMedGoogle Scholar
  49. 49.
    Sperling RI, Benincaso AI, Knoell CT, Larkin JK, Austen KF, Robinson DR, et al. Dietary n-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Investig. 1993;91:651–60.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable or fish oil. Am J Clin Nutr. 1996;63:116–22.PubMedGoogle Scholar
  51. 51.
    Bannenberg G, Serhan CN. Specialized pro-resolving lipid mediators in the inflammatory response: an update. Biochim Biophys Acta. 2010;1801:1260–73. Scholar
  52. 52.
    Poreba M, Mostowik M, Siniarski A, Golebiowska-Wiatrak R, Malinowski KP, Haberka M, et al. Treatment with high-dose n-3 PUFAS has no effect on platelet function, coagulation, metabolic status or inflammation in patients with atherosclerosis and type 2 diabetes. Cardiovasc Diabetol. 2017;16:50. Scholar
  53. 53.
    Yamakawa K, Shimabukuro M, Higa N, Asahi T, Ohba K, Arasaki O, et al. Eicosapentaenoic acid supplementation changes fatty acid composition and corrects endothelial dysfunction in hyperlipidemic patients. Cardiol Res Pract. 2012;2012:754181. Scholar
  54. 54.
    Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman CP, et al. Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet. 2003;361(9356):477–85. Scholar
  55. 55.
    Nishio R, Shinke T, Otake H, Nakagawa M, Nagoshi R, Inoue T, et al. Stabilizing effect of combined eicosapentaenoic acid and statin therapy on coronary thin-cap fibroatheroma. Atherosclerosis. 2014;234(1):114–9. Scholar
  56. 56.
    Yamano T, Kubo T, Shiono Y, Shimamura K, Orii M, Tanimoto T, et al. Impact of eicosapentaenoic acid treatment on the fibrous cap thickness in patients with coronary atherosclerotic plaque: an optical coherence tomography study. J Atheroscler Thromb. 2015;22(1):52–61. Scholar
  57. 57.
    Doi H, Kugiyama K, Oka H, Sugiyama S, Ogata N, Koide SI, et al. Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism. Circulation. 2000;102(6):670–6. Scholar
  58. 58.
    Vanschoonbeek K, Feijge MA, Paquay M, Rosing J, Saris W, Kluft C, et al. Variable hypocoagulant effect of fish oil intake in humans: modulation of fibrinogen level and thrombin generation. Arterioscler Thromb Vasc Biol. 2004;24:1734–40. Scholar
  59. 59.
    McEwen BJ, Morel-Kopp MC, Tofler GH, Ward CM. The effect of omega-3 polyunsaturated fatty acids on fibrin and thrombin generation in healthy subjects and subjects with cardiovascular disease. Semin Thromb Hemost. 2015;41(3):315–22. Scholar
  60. 60.
    Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, 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):1090–8. Scholar
  61. 61.
    Begtrup KM, Krag AE, Hvas AM. No impact of fish oil supplements on bleeding risk: a systematic review. Dan Med J. 2017;64(5):A5366.PubMedGoogle Scholar
  62. 62.
    Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation. 2005;112(13):1945–52. Scholar
  63. 63.
    Wang Q, Liang X, Wang L, Lu X, Huang J, Cao J, et al. Effect of omega-3 fatty acids supplementation on endothelial function: a meta-analysis of randomized controlled trials. Atherosclerosis. 2012;221(2):536–43. Scholar
  64. 64.
    Weisman D, Beinart R, Erez A, Koren-Morag N, Goldenberg I, Eldar M, et al. Effect of supplemented intake of omega-3 fatty acids on arrhythmias in patients with ICD: fish oil therapy may reduce ventricular arrhythmia. J Interv Card Electrophysiol. 2017;49(3):255–61. Scholar
  65. 65.
    Jenkins DJ, Josse AR, Dorian P, Burr ML, LaBelle TR, Kendall CW, et al. Heterogeneity in randomized controlled trials of long chain (fish) omega-3 fatty acids in restenosis, secondary prevention and ventricular arrhythmias. J Am Coll Nutr. 2008;27(3):367–78.CrossRefPubMedGoogle Scholar
  66. 66.
    Khoueiry G, Abi Rafeh N, Sullivan E, Saiful F, Jaffery Z, Kenigsberg DN, et al. Do omega-3 polyunsaturated fatty acids reduce risk of sudden cardiac death and ventricular arrhythmias? A meta-analysis of randomized trials. Heart Lung. 2013;42(4):251–6. Scholar
  67. 67.
    Mozaffarian D, Marchioli R, Macchia A, Silletta MG, Ferrazzi P, Gardner TJ, et al. Fish oil and post-operative atrial fibrillation: the Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) randomized trial. JAMA. 2012;308:2001–11. Scholar
  68. 68.
    Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: meta-regression analysis of randomized trials. J Hypertens. 2002;20(8):1493–9.CrossRefPubMedGoogle Scholar
  69. 69.
    Miller PE, Van Elswyk M, Alexander DD. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials. Am J Hypertens. 2014;27(7):885–96. Scholar
  70. 70.
    Minihane AM, Armah CK, Miles EA, et al. Consumption of fish oil providing amounts of eicosapentaenoic acid and docosahexaenoic acid that can be obtained from the diet reduces blood pressure in adults with systolic hypertension: a retrospective analysis. J Nutr. 2016;146(3):516–23. Scholar
  71. 71.
    Friedberg C, Janssen M, Heine R, Grobbee D. Fish oil and glycemic control in diabetes: a meta-analysis. Diabetes Care. 1998;21:494–500.CrossRefPubMedGoogle Scholar
  72. 72.
    Mori T, Burke V, Puddey IB, Shaw JE, Berlin L. Effect of fish diets and weight loss on serum leptin concentration in overweight, treated hypertensive subjects. J Hypertens. 2004;22:1983–90.CrossRefPubMedGoogle Scholar
  73. 73.
    Helland A, Bratlie M, Hagen IV, Mjos SA, Sornes S, Ingvar Halstensen A, et al. High intake of fatty fish, but not lean fish, improved postprandial glucose regulation and increased the n-PUFA content in the leucocyte membrane in healthy overweight adults: a randomised trial. Br J Nutr. 2017;117(10):1368–78. Scholar
  74. 74.
    Methodology manual and policies. From the ACCF/AHA Task Force on Practice Guidelines. June 2010. Available at Accessed August 3, 2017.Google Scholar
  75. 75.
    Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, et al. The VITamin D and OmegA-3 Trial (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012;33(1):159–71. Scholar
  76. 76.
    ORIGIN Trial Investigators, Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, et al. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012;367:309–18. Scholar
  77. 77.
    Risk and Prevention Study Collaborative Group, Roncaglioni MC, Tombesi M, Avanzini F, Barlera S, Caimi V, et al. n-3 fatty acids in patients with multiple cardiovascular risk factors [published correction appears in N Engl J Med. 2013;368:2146]. N Engl J Med. 2013;368:1800–8. Scholar
  78. 78.
    Writing Group for the AREDS2 Research Group, Bonds DE, Harrington M, Worrall BB, Bertoni AG, Eaton CB, et al. Effect of long-chain ω-3 fatty acids and lutein + zeaxanthin supplements on cardiovascular disease outcomes: results of the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA Intern Med. 2014;174:763–71. Scholar
  79. 79.
    GISSI-Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico). Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354(9177):447–55.CrossRefGoogle Scholar
  80. 80.
    Kromhout D, Giltay EJ, Geleijnse JM, for the Alpha Omega Trial Group. N-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015–26. Scholar
  81. 81.
    Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet and Reinfarction Trial (DART). Lancet. 1989;2:757–61.CrossRefPubMedGoogle Scholar
  82. 82.
    Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, 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;122:2152–9. Scholar
  83. 83.
    Galan P, Kesse-Guyot E, Czemichow S, Briancon S, Blacher J, Hercberg S, et al. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ. 2010;341:c6273. Scholar
  84. 84.
    Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systemic review and meta-analysis. JAMA. 2012;308:1024–33. Scholar
  85. 85.
    ASCEND: A Study of Cardiovascular Events iN Diabetes. Available at Accessed August 1, 2017.
  86. 86.
    Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1223–30. Scholar
  87. 87.
    Alexander DD, Miller PE, Van Elswyk ME, Kuratko CN, Bylsma LC. A meta-analysis of randomized controlled trials and prospective cohort studies of eicosapentaenoic and docosahexaenoic long-chain omega-3 fatty acids and coronary heart disease risk. Mayo Clin Proc. 2017;92(1):15–29. Scholar
  88. 88.
    Casula M, Soranna D, Catapano AL, Corrao G. Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: a meta-analysis of randomized, placebo controlled trials [corrected]. Atheroscler Suppl. 2013;14(2):243–51.CrossRefPubMedGoogle Scholar
  89. 89.
    Bhatt DL, Steg PG, Brinton EA, Jacobson TA, Miller M, Tardif JC, et al. Rationale and design of REDUCE-IT: Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial. Clin Cardiology. 2017;40:138–48. Scholar
  90. 90. 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). Available at Accessed July 7, 2017.
  91. 91. Outcomes study to assess statin residual risk reduction with Epanova in high CV risk patients with hypertriglyceridemia (STRENGTH). Available at Accessed July 7, 2017.
  92. 92.
    Kris-Etherton PM, Harris WS, Appel LJ, for the American Heart Association, Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106(21):2747–57. Scholar
  93. 93.
    Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2292–333. Scholar
  94. 94.
    Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol. 2015;9(2):129–69. Scholar
  95. 95.
    Jacobson TA, Maki KC, Orringer CE, Jones PH, Kris-Etherton PM, Sikand G, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9(6 Suppl):S1–122.e1. Scholar
  96. 96.
    Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969–89. Scholar
  97. 97.
    The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999–3058. Scholar
  98. 98.
    National Institutes of Health, National Center for Complementary and Integrative Health. Using dietary supplements wisely. Available at Accessed August 4, 2017.

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Megan F. Burke
    • 1
  • Frances M. Burke
    • 2
  • Daniel E. Soffer
    • 3
    Email author
  1. 1.Department of MedicineUniversity of Pennsylvania Health SystemPhiladelphiaUSA
  2. 2.Department of Medicine, Division of CardiologyUniversity of Pennsylvania Health SystemPhiladelphiaUSA
  3. 3.Department of Medicine, Divisions of Internal Medicine and Cardiology, Perelman Center for Advanced MedicineUniversity of Pennsylvania Health SystemPhiladelphiaUSA

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