NLA 2025: Managing Omega-3 Therapy With Statins, PCSK9 Inhibitors for Cardiovascular Care

As the landscape of cardiovascular disease management continues to evolve, understanding the diverse mechanisms and therapeutic roles of omega-3 fatty acids is essential for optimizing patient care. Omega-3 therapies, including icosapent ethyl (Vascepa; Amarin), have demonstrated cardiovascular benefits in large clinical trials, yet questions remain about how best to integrate these agents alongside established therapies, such as statins and PCSK9 inhibitors.

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 on key considerations for managing omega-3 therapy. In this interview with Pharmacy Times®, Qian offers insights into potential drug interactions, non-lipid mechanisms of benefit—such as anti-inflammatory and anti-thrombotic effects—and areas for future research. Qian highlights the nuanced role of omega-3 fatty acids in cardiovascular care and underscores the importance of a comprehensive, individualized approach to lipid management.

Pharmacy Times: How do you recommend managing omega-3 therapy in patients already on statins or PCSK9 inhibitors—are there concerns about additive lipid-lowering effects or drug interactions?

Omega-3 fatty acids. Image Credit: © LimeSky - stock.adobe.com

Frank Qian, MD, MPH: I think all the contemporary omega-3 fatty acid trials, including REDUCE-IT [NCT01492361] and RESPECT-EPA [NCT03014548], were conducted predominantly in patients already on high-intensity statins. So, there’s no concern that there would be any issues with lipid-lowering, particularly because we think about statins as predominantly LDL-lowering agents, whereas omega-3 therapies are more for targeting triglycerides. Although, to anticipate some of your following questions, there are a lot of other mechanisms potentially at play for why we’re seeing these cardiovascular benefits. For PCSK9 inhibitors, a lot of the patients in these trials were not necessarily on PCSK9 inhibitors, so I don’t think they’re necessarily mutually exclusive. One of the guidelines I’ll discuss during my presentation is the American College of Cardiology Expert Consensus Pathway for triglyceride management, which notes that if a patient has both elevated LDL cholesterol—on statins—and elevated triglycerides, it’s reasonable to consider both approaches. You might think about adding a PCSK9 inhibitor as well as a therapy such as icosapent ethyl. I don’t think they’re mutually exclusive. Ultimately, it comes down to whether the patient can tolerate polypharmacy, whether the costs are acceptable—those kinds of considerations. But there’s no strong evidence of significant drug-drug interactions between these therapies, as they’re really targeting distinct pathways.

Pharmacy Times: What role do omega-3 fatty acids play in non-lipid cardiovascular effects, such as anti-inflammatory or anti-thrombotic activity, and how might this influence future research directions?

Qian: Absolutely. A lot of the original work by Danish investigators, for example, studies of the Greenland Eskimos, focused on the potential cardiovascular benefits of omega-3 fatty acids, including their effects on platelet function—specifically in reducing platelet aggregation and thrombotic risk. Those early observations also noted a bleeding risk, which has been seen in some of the more recent omega-3 trials. There’s definitely a component of the benefit that’s related to antithrombotic effects. A lot of the early research also explored the anti-arrhythmic properties of omega-3 fatty acids, particularly in stabilizing ventricular membranes. The hypothesis was that because these fatty acids integrate into cellular membranes, especially those in myocardial tissue, they help stabilize the membranes in the setting of ischemic insult, such as a myocardial infarction. This stabilization could reduce the risk of arrhythmias like ventricular tachycardia or fibrillation. Some of the early trials suggested that prevention of sudden cardiac death may have been one of the key pathways through which omega-3 fatty acids conferred benefit. That effect was also seen in REDUCE-IT, where they observed a significant reduction in cardiac arrest—a stronger signal, in fact, than for overall cardiovascular mortality.

Regarding anti-inflammatory effects, there is evidence that omega-3 fatty acids may lower inflammatory biomarkers like high-sensitivity C-reactive protein. Beyond that, they may influence other pathways, such as thromboxane synthesis, where they can compete with arachidonic acid metabolites, potentially modifying inflammatory cascades. They are also known to be precursors for specialized pro-resolving mediators—these molecules don’t just suppress inflammation but help resolve it, which is a distinct mechanism compared to direct anti-inflammatory action. So, while we often focus on triglyceride lowering, there’s a growing understanding that the benefits of omega-3 fatty acids likely extend beyond that. Many of the cardiovascular benefits may be attributable to these additional mechanisms, which are still being actively studied. For instance, trials such as CHERRY and RESPECT-EPA enrolled patients not necessarily because of high triglycerides but because of elevated cardiovascular risk, and they still observed benefits. I think there’s a lot still to learn in this area, and it remains a very promising field for future research.