Managing Hypertriglyceridemia With Omega-3 Fatty Acids: An AHA Advisory

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The advisory from the American Heart Association aggregates the research performed thus far on the use of omega-3 fatty acids in hypertriglyceridemia and recommends a dose of 4 g/d to observe a therapeutic effect.

According to a science advisory from the American Heart Association published in Circulation, 4 g/d of omega-3 fatty acids is a safe and effective treatment for hypertriglyceridemia, both alone and as adjunct therapy to other lipid-lowering agents.

Researchers released this advisory as a summary of the lipid and lipoprotein effects of pharmacologic doses (>3 g/d) of omega-3 fatty acids, particularly the efficacy of omega-3 fatty acids in reducing severe levels of plasma triglycerides (≥500 mg/dL). In 2002, the American Heart Association recommended 2 to 4 g/d for total omega-3 intake (referring to eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) for triglyceride lowering. Since then, the United States Food and Drug Administration has approved prescription agents containing these components together or EPA alone.

In treating severely elevated triglycerides with 4 g/d of omega-3 fatty acids, agents with EPA and DHA have been found to reduce triglycerides by at least 30% with simultaneous increases in low-density lipoprotein cholesterol. However, icosapent ethyl, which consists only of EPA, did not increase low-density lipoprotein cholesterol levels.

In treating hypertriglyceridemia, omega-3 fatty acids with EPA and DHA or EPA only have been deemed similarly effective and safe in lowering triglycerides. They do not elevate low-density lipoprotein cholesterol when used alone or paired with a statin. Thus far, researchers have found that 4 g/d of an omega-3 fatty acid modestly decreases non-high-density lipoprotein cholesterol and apolipoprotein B levels, which suggests total atherogenic lipoprotein reduction.

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Furthermore, in a randomized placebo-controlled trial of icosapent ethyl in patients with hypertriglyceridemia who were at high risk for atherosclerotic cardiovascular disease and treated with a statin, the addition of 4 g/d of an omega-3 fatty acid reduced risk for major adverse cardiovascular events by up to 25% ( Identifier: NCT01492361). Results from a similar trial of a 4-g/d prescription EPA and DHA can be expected in 2020 ( Identifier: NCT02104817).

“The triglyceride-lowering efficacy and generally excellent safety and tolerability of [omega-3 fatty acids] make them valuable tools for healthcare providers,” the authors wrote in the advisory. In clinical trials completed to date, <5% of patients have stopped taking omega-3 fatty acid agents because of side effects, which may include fishy taste, eructation, diarrhea, and nausea.

Overall, omega-3 fatty acids “are clinically useful for reducing triglycerides, after any underlying causes are addressed and diet and lifestyle strategies are implemented,” according to the advisory panel.

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Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: a science advisory from the American Heart Association [published online August 19, 2019]. Circulation. doi:10.1161/CIR.0000000000000709