Randomized trials of omega-3 treatments have shown mixed evidence. While some initial studies suggested benefit with low-dose omega-3 fatty acids, subsequent trials in populations with contemporary medical therapy generally showed no significant benefit. High-dose eicosapentaenoic acid (EPA) has demonstrated more consistent benefits in recent trials, particularly in reducing cardiovascular events among individuals with elevated triglycerides.

Icosapent ethyl (IPE) has FDA approval for triglyceride reduction and as an adjunct to statin therapy among individuals with elevated triglycerides and cardiovascular risk factors. It is also indicated for severe hypertriglyceridemia. Various guidelines provide recommendations for the use of IPE in specific populations based on triglyceride levels, cardiovascular risk factors, and history of cardiovascular disease.

Low-dose omega-3 fatty acids are generally well tolerated, while high-dose treatments may be associated with an increased risk of gastrointestinal disorders, atrial fibrillation, and minor bleeding. Allergic individuals should avoid fish-derived omega-3 products. The safety profile of IPE, believed to be highly purified, remains uncertain for allergic individuals.

Omega-3 fatty acids have shown cost-effectiveness for various cardiovascular scenarios, including secondary prevention. However, conflicting data exist regarding the cost-effectiveness of icosapent ethyl, with some studies suggesting it is cost-effective for secondary prevention of ischemic cardiovascular events while others indicate it may not be.