Omega-3 Fatty Acid and Cardiovascular Outcomes: Insights From Recent Clinical Trials
Purpose of Review
Omega-3 fatty acids (ω-3 FA) are among the most well-recognized health supplements but their cardiovascular benefits have long been controversial owing to inconsistent results from previous cardiovascular outcomes trials (CVOT). In this article, we provide a short review of existing literature followed by recent randomized clinical trial data, with a discussion of the potential clinical implications of these new findings.
Data from the randomized, controlled trial REDUCE-IT, when viewed within the context of other recently published trials ASCEND and VITAL, add to a growing body of evidence on the use of ω-3 FA therapies in the treatment of atherosclerotic cardiovascular disease (ASCVD).
Given the different formulations, dosages, and patient populations studied, CVOTs of ω-3 FA have provided valuable insight into the use of these agents in cardioprotection. Current data suggest that higher dosages of pure eicosapentaenoic acid ω-3 FA formulations provide additional benefit in reduction of ASCVD events.
KeywordsOmega-3 fatty acid Eicosapentaenoic acid Docosahexaenoic acid Icosapent ethyl Cardiovascular outcomes Lipids
Compliance with Ethical Standards
Conflict of Interest
Xiaoming Jia, Payal Kohli, Salim S. Virani declare no conflict of interest.
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
- 8.Brenna JT, Salem N, Sinclair AJ, Cunnane SC. International Society for the Study of fatty acids and Lipids ISSF. Alpha-linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fat Acids. 2009;80(2–3):85–91.CrossRefGoogle Scholar
- 10.US Food & Drug Administration. Approval package for application number 21–654. 2004.Google Scholar
- 11.US Food & Drug Administration. Approval package for: application number 202057Orig1s000. 2012.Google Scholar
- 16.•• Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, et al. Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus. N Engl J Med. 2018;379(16):1540–50. Large CVOT of ω-3 FA in primary prevention of ASCVD in patients with diabetes showing no significance in reduction of primary endpoint in the active treatment arm compared with placebo. CrossRefGoogle Scholar
- 17.•• Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, et al. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019;380(1):23–32. Large CVOT of ω-3 FA with and without vitamin D in primary prevention of ASCVD no significance in reduction of primary endpoint in the active treatment arm compared with placebo. Google Scholar
- 18.•• Bhatt DL, Steg G, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22. CVOT of highly pure EPA ethyl ester, icosapent ethyl, showing reduction in primary efficacy endpoint compared with placebo. Google Scholar
- 19.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):447–55.Google Scholar
- 22.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(21):2152–9.CrossRefGoogle Scholar
- 36.• Nicholls SJ, Lincoff AM, Bash D, Ballantyne CM, Barter PJ, Davidson MH, et al. Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial. Clin Cardiol. 2018;41(10):1281–8. Ongoing CVOT of ω-3 FA assessing efficacy of 4g/day of EPA+DHA mixture in reduction of ASCVD events. CrossRefGoogle Scholar
- 38.Saito Y, Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, 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.CrossRefGoogle Scholar
- 44.London B, Albert C, Anderson ME, Giles WR, Van Wagoner DR, Balk E, et al. Omega-3 fatty acids and cardiac arrhythmias: prior studies and recommendations for future research: a report from the National Heart, Lung, and Blood Institute and office of dietary supplements Omega-3 fatty acids and their role in cardiac Arrhythmogenesis workshop. Circulation. 2007;116(10):e320–35.CrossRefGoogle Scholar
- 47.Jia X, Miedema M, Virani SS, Kohli P. Not all fish oils are created equal: insight from REDUCE-IT. 2018. https://www.acc.org/latest-in-cardiology/articles/2018/11/14/13/59/not-all-fish-oils-are-created-equal. Accessed on 30 Nov 2018.