NLA 2025: Exploring the Evidence Behind Omega-3 Fatty Acids for Cardiovascular Risk

Omega-3 fatty acids have long been recognized for their role in lipid management, but their clinical applications, particularly for cardiovascular risk reduction, continue to evolve. At the 2025 National Lipid Association (NLA) Scientific Sessions in Miami, Florida, Frank Qian, MD, MPH, a cardiovascular medicine fellow at Boston Medical Center in Massachusetts, spoke in a session titled “Omega-3 Fatty Acids.” In this interview, Pharmacy Times® spoke with Qian to discuss the current clinical indications for prescription omega-3 fatty acids, the differences between formulations, and the ongoing debate surrounding trial outcomes and placebo effects in cardiovascular research.

Pharmacy Times: What are the current clinical indications for prescription omega-3 fatty acids?

Frank Qian, MD, MPH: There are a couple of different indications for prescription omega-3 fatty acids, depending on the clinical context. One is for hypertriglyceridemia, and there are 2 different FDA-approved strategies here. The first involves using a mixture of omega-3 fatty acids—specifically, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—at a dose of 2 to 4 grams per day. This formulation is typically used for patients with severe hypertriglyceridemia, usually defined as triglyceride levels greater than 500 mg/dL. The second indication is specifically for cardiovascular disease risk reduction, and that uses a purified EPA-only formulation, icosapent ethyl. This is usually dosed at 4 grams per day—taken as 2 grams twice daily—and is indicated for patients with persistent hypertriglyceridemia in the 150 to 499 mg/dL range who are already on maximally tolerated statin therapy.

A bottle of soft gel capsules containing omega-3 fatty acids. Image Credit: © Chandlerlikes - stock.adobe.com

Pharmacy Times: Can you summarize key findings from recent clinical trials and how they have shaped current recommendations for omega-3 fatty acids?

Qian: I think it's important to step back and consider why the more recent large-scale cardiovascular outcomes trials have focused on higher doses of omega-3 fatty acids. Many of the earlier trials used lower doses, typically less than or equal to 1 gram per day, and often included mixtures of EPA and DHA. The more recent trials have shifted to higher doses—greater than 1 gram per day—and have tested different formulations. For example, in the REDUCE-IT trial, they used 4 grams per day (2 grams twice daily) of icosapent ethyl, which is a purified EPA product. That trial showed a significant benefit in reducing cardiovascular events. However, there has been ongoing controversy in the field, particularly because REDUCE-IT used mineral oil as the placebo, which some believe may have had negative effects on the control group.

Following REDUCE-IT, 2 other major trials—STRENGTH and [Omega-3 Fatty acids in Elderly with Myocardial Infarction (OMEMI)]—tested higher doses of omega-3 fatty acids. The STRENGTH trial used 4 grams per day of a combination of EPA and DHA, and the OMEMI trial used 1.8 grams per day of a similar EPA-DHA combination. Neither trial showed a benefit for cardiovascular outcomes with these higher doses of mixed omega-3 formulations compared to placebo.

More recently, the RESPECT-EPA trial was conducted in Japan as something of a successor to the original [Japan EPA Lipid Intervention Study (JELIS)] trial. Like JELIS, RESPECT-EPA tested 1.8 grams per day of purified EPA and found a modest, though not statistically significant, reduction in the primary endpoint. However, RESPECT-EPA did show a benefit in several secondary endpoints, particularly coronary disease outcomes, with about a 25% relative risk reduction—similar to what was seen in REDUCE-IT. Some experts argue that, when you look at the totality of data from JELIS, RESPECT-EPA, and REDUCE-IT, the cardiovascular benefit of purified EPA appears to be real. It's worth noting that both JELIS and RESPECT-EPA did not use mineral oil as a placebo, so those results are less subject to the concerns raised about the potential harms of the mineral oil placebo used in REDUCE-IT.