REVIEWN-3 polyunsaturated fatty acids for cardiovascular riskGoff, Zackary D.; Nissen, Steven E. Author Information Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA Correspondence to Steven E. Nissen, MD, Cleveland Clinic Heart, Vascular, and Thoracic Institute, Sydell & Arnold Miller Family Pavilion, 9500 Euclid Ave, Cleveland, OH 44195, USA. E-mail: [email protected] Current Opinion in Cardiology ():10.1097/HCO.0000000000000962, July 12, 2022. | DOI: 10.1097/HCO.0000000000000962 Buy PAP Metrics Abstract Purpose of review Use of omega-3 fatty acid (OM3FA) supplements to reduce risk of cardiovascular events has been investigated, largely without evidence of meaningful benefit, over the last 4 decades. Recent findings The first contemporary clinical trial to show benefit of OM3FA use was the REDUCE-IT trial (2018), showing a remarkable 25% relative risk reduction in the intervention group that received icosapent ethyl 4 g daily compared to a mineral oil placebo group. The STRENGTH trial (2020), which was similar in design to the REDUCE-IT trial but compared 4 g daily dose of combined OM3FA with a corn oil placebo, was terminated early due to futility. Summary This article provides a review of the data surrounding these trials and discusses the differing results of the two trials. There are key differences in the design of the two trials, the most notable is the use of mineral oil in the REDUCE-IT trial, which was potentially a nonneutral comparator. Additionally, both trials showed an increase in the incidence of atrial fibrillation. With the unclear benefit of OM3FA supplementation and possibility of harm, the current data suggest that the risk of routine use of OM3FA outweighs the possibility of reduction in risk of cardiovascular events. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.