AHA Advisory Backs Prescription Omega-3s for Triglycerides

Megan Brooks

August 23, 2019

Prescription omega-3 fatty acids — products containing eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) or EPA alone — are an "effective and safe" way to reduce elevated triglyceride levels when used alone or with other lipid-lowering therapy, according to a science advisory from the American Heart Association (AHA).

The triglyceride-lowering efficacy and generally excellent degree of safety and tolerability of prescription-strength omega-3 fatty acids make them "valuable tools for healthcare providers," write Ann Skulas-Ray, PhD, Department of Nutritional Sciences, University of Arizona in Tucson, and colleagues on the advisory panel.

Dietary supplements containing omega-3 fatty acids, which are not regulated by the US Food and Drug Administration (FDA), should not be used in place of prescription medication for the long-term management of high triglyceride levels, they say.

The advisory was published online August 19 in Circulation.

Triglyceride Lowering and CV Protection

The 2002 AHA scientific statement on fish and omega-3 fatty acids recommended increased intake of dietary omega-3 plus dietary supplements to achieve a level of 2 to 4 g/day of omega-3 fatty acids (referring to the total amount of EPA and DHA) for triglyceride lowering under the supervision of a physician. At the time, no prescription omega-3 fatty acids were available.

Since then, two prescription omega-3 fatty acid medications have become available in the United States. One combines EPA and DHA (Lovaza, GlaxoSmithKline). The other provides EPA only (Vascepa, Amarin). They are indicated for treating very high triglyceride (VHTG) levels (≥500 mg/dL), although these agents are also widely used for hypertriglyceridemia (triglyceride levels of 200 – 499 mg/dL), the advisory panel notes.

The advisory summarizes the lipid and lipoprotein effects resulting from use of pharmacologic doses of omega-3 fatty acids on the basis of new scientific data and the availability of these agents.

Prescription omega-3 fatty acids at the FDA-approved dose of 4 g/day are safe and are generally well tolerated, the advisory states. In clinical trials of adults with VHTG, EPA+DHA at this dose reduced triglycerides by ≥30% and concurrently increased low-density lipoprotein (LDL) cholesterol levels, whereas EPA alone did not increase LDL cholesterol.

For patients with VHTG, the goal of therapy is to lower triglyceride levels to <500 mg/dL and to lessen the risk for pancreatitis, although this may not be achieved with omega-3 fatty acid monotherapy. Additional triglyceride-lowering pharmacologic treatment may be needed, the panel says.

For patients with triglyceride levels from 200 – 499 mg/dL, prescription omega-3 fatty acids at a dose of 4 g/day reduce triglyceride levels by 20% to 30% without significantly increasing LDL cholesterol, they note. For these patients, EPA alone and EPA+DHA are roughly comparable for lowering triglyceride levels.

In the largest trials of prescription omega-3 fatty acids at a dose of 4 g/day, non–high-density lipoprotein (HDL) cholesterol levels and apolipoprotein B levels were modestly decreased, indicating reductions in total atherogenic lipoprotein level, the panel reports.

The authors emphasize that medical conditions such as poorly controlled type 2 diabetes, hypothyroidism, and obesity that may contribute to elevations in triglyceride levels should be addressed before use of prescription medications.

Use of omega-3 fatty acids may be accompanied by mild gastrointestinal complaints (such as "fishy burps" or nausea). Taking omega-3s with meals may reduce these side effects and improve absorption. In clinical trials, fewer than 5% of patients stopped taking these agents because of side effects.

The authors note that use of omega-3 fatty acids (4 g/day) for lowering risk for atherosclerotic cardiovascular disease for patients with elevated triglyceride levels is supported by the landmark REDUCE-IT trial, which found a 25% reduction in major adverse cardiovascular events among high-risk patients receiving statin therapy and the EPA-only product.

On the basis of the REDUCE-IT results, Amarin has submitted a supplemental new drug application to the FDA to expand the indication for the product to include cardiovascular risk reduction. On August 14, the agency announced that it plans to put the application before an advisory committee in mid-November. The move is expected to extend the Prescription Drug User Fee Act (PDUFA) date for the new indication by about 3 months, from September 28 to late December, Amarin said in a statement.

Results from the STRENGTH trial, a randomized, placebo-controlled cardiovascular outcomes trial of the use of prescription EPA+DHA 4 g/day for patients with high triglyceride levels and low HDL cholesterol levels who are taking statins, are expected next year.

The AHA advisory does not recommend one prescription omega-3 product over the other because there have been no head-to-head comparisons of the two different formulations at prescription doses.

The AHA currently recommends that adults consume two 3.5-oz servings of nonfried fish (or about three fourths of a cup of flaked fish) per week, preferably oily fish, such as salmon, mackerel, herring, lake trout, sardines, or albacore tuna, which are all high in omega-3 fatty acids.

The research had no commercial funding. Disclosures for the advisory panel members are listed with the original article.

Circulation. Published online August 19, 2019. Abstract

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