Assessing Omega-3 Therapy and Its Cardiovascular Benefits: What About Icosapent Ethyl? A Systematic Review and Meta-Analysis

Abstract

Background: Lipid-lowering therapies are an option for stabilizing lipid levels. Icosapent ethyl (IPE) is a highly purified formulation of eicosapentaenoic acid, which can reduce lipid action, improve plaque stabilization, reduce platelet aggregation, lower TG, and prevent cardiovascular events. IPE is frequently used with statins to manage elevated TG levels. However, the evidence on IPE as a lipid-lowering agent is limited, and no updated systematic review and meta-analysis have been published considering the recent advancements in the field and newly published studies. Therefore, we aim to fill this gap. Methods: We used the PRISMA guidelines and the PICO (Population, Intervention, Comparison, and Outcome) framework to conduct this review, aiming to answer the question, "Can IPE benefit patients at cardiovascular risk?" GRADE was used to evaluate evidence levels to adhere to the highest criteria. Results: Predominantly, the evaluated population presented TG levels between ≥135 mg/dL and 500 mg/dL and LDL-C levels between >40 mg/dL and ≤100 mg/dL. The included studies showed a reduction in TG and LDL-C and a decrease in cardiovascular events. It means that, according to our systematic review evidence analysis, IPE has been effective in lowering blood lipid levels, including TG, and reducing cardiovascular death and events, such as non-fatal stroke or hospitalization for unstable angina. However, it is worth noting that these results were primarily from patients undergoing statin therapy. According to our meta-analysis, IPE may not be considered a lipid-lowering drug, as limited action associated with its use was evident in the quantitative results. However, caution is necessary, as only two studies were suitable for inclusion due to the differing outcomes in the analyzed samples. Conclusions: Despite the quantitative synthesis, IPE possesses anti-inflammatory, anti-thrombotic, and anti-atherogenic properties, highly related to cardiovascular protection. Based on our included studies, IPE was considered a promising therapy for atherosclerotic cardiovascular disease in conjunction with other lipid-lowering therapies, particularly statins, for patients with extremely high TG levels. The limitations of the reviewed studies may include small sample sizes, varying outcomes, and a small duration of interventions. Future clinical trials with similar outcomes, sample sizes, and intervention durations must be designed, and updated meta-analyses must be published in the following years to fully assess the effects of IPE as a lipid-lowering and cardiovascular protector drug.