History and future of omega-3 fatty acids in cardiovascular disease

Abstract

Background/objectives:

Epidemiological, diet-based, and some interventional outcomes studies suggest that polyunsaturated omega-3 fatty acids (OM3FAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), confer cardiovascular protection in some patient populations. This review examines the historical context of OM3FAs in cardiovascular disease and future perspectives on the place of OM3FA products in reducing cardiovascular risk.

Methods:

Relevant articles were identified via PubMed/Medline and Google Scholar searches through 2015 and through reference lists of selected publications. Articles determined by the authors to be relevant to the topic of this review were included.

Results:

Review of the identified articles indicated that inconsistent results among interventional outcomes studies have been attributed to use of low doses of OM3FAs, patient cohorts with non-elevated triglyceride (TG) levels, differential use of concomitant statin therapy, and study designs with insufficient statistical power. Several prescription OM3FA products are now approved as an adjunct to diet to reduce TG levels in adults with severe (≥500 mg/dL) hypertriglyceridemia. Most formulations contain both EPA and DHA; one formulation contains purified EPA. In randomized controlled trials, these products significantly reduced TG levels in patients with very high TG levels (≥500 mg/dL [≥13.0 mmol/L]) and in statin-treated patients with high TG levels (200–499 mg/dL [5.2–12.9 mmol/L]). The DHA-containing products raised LDL-C levels in these studies, whereas the EPA-only product had no effect on LDL-C, suggesting that all OM3FA prescription products are not therapeutically equivalent. Besides lowering TG levels, OM3FAs (particularly EPA) exert anti-inflammatory effects and may slow multiple atherogenic processes. Two well designed interventional outcomes studies (REDUCE-IT and STRENGTH) are evaluating prescription-strength, high-dose OM3FAs (4 g/day) in statin-treated patients with persistently high TG levels.

Conclusions:

The results of the ongoing prescription-strength, high-dose OM3FA interventional trials will help define the potential role of OM3FAs in addressing residual cardiovascular risk despite statin therapy.

Keywords: :

• Atherosclerosis
• Docosahexaenoic acid
• Eicosapentaenoic acid
• Omega-3 fatty acids
• Triglycerides

Transparency

Declaration of funding

This review was funded by Amarin Pharma Inc.

Declaration of financial/other relationships

L.S.S. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article. J.R.N. has disclosed that he has received grant/research support from Amarin Pharma Inc.; has served on speakers’ bureau for Amarin Pharma Inc., Amgen, Regeneron, AstraZeneca, Kowa, and Arbor; has served as a consultant to Amarin Pharma Inc., Amgen, Regeneron, and AstraZeneca; is a stock shareholder of Amarin Pharma Inc., Amgen, Regeneron, and Pfizer; and has participated in formal advisory activities for Amarin Pharma Inc., Regeneron, AstraZeneca, and Kowa.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work. Peer reviewer 1 has disclosed that he has received grants from ProNova and is a consultant to Aker BioMarine, Solutex, Sancilio, DSM, and Danone. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

Medical writing assistance was provided by Peloton Advantage, Parsippany, NJ, USA and was funded by Amarin Pharma Inc. Medical scientific reference checks and associated assistance were provided by Sephy Philip RPH PharmD and P. Benjamin Everett PhD of Amarin Pharma Inc., Bedminster, NJ, USA.

Notes

*Lovaza is a registered trade name of Glaxo-SmithKline, Research Triangle Park, NC, USA

**Omtryg is a registered trade name of Trygg Pharma Inc., Arlington, VA, USA

†Epanova is a registered trade name of AstraZeneca Pharmaceuticals, Wilmington, DE, USA

‡Vascepa is a registered trade name of Amarin Pharma Inc., Bedminster, NJ, USA