Meta-Analysis of 19 Clinical Trials using Omega-3 Fatty Acids Indicate Distinct Outcomes for Icosapent Ethyl

Abstract

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> Consumption of the omega-3 fatty acids (O3FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been associated with a lower risk of cardiovascular disease (CVD). However, randomized clinical trials have failed to show consistent benefit with O3FAs in patients receiving contemporary medical care. Recent trials suggest that the formulation may have an important influence on clinical outcomes. <h3>Objective/Purpose</h3> We conducted a meta-analysis of 19 trials using both mixed O3FA products as well as prescription icosapent ethyl (IPE), which is the ethyl ester of EPA. <h3>Methods</h3> The current meta-analysis includes 15 randomized controlled trials with endpoints including non-fatal myocardial infarction (MI), coronary heart disease (CHD) death, total CHD, CVD death, total CVD, total stroke and major vascular events. The pooled rate ratios (RRs) were calculated using a fixed method. This meta-analysis also includes 4 clinical trials that assess the effect of O3FAs on coronary plaque volume and stability. All trials involved formulations with EPA alone (IPE) or in combination with DHA. <h3>Results</h3> Out of 19 trials using omega-3 fatty acids in patients with CVD risk, 5 of them employed IPE, all of which (100%) met the defined endpoints in statin treated patients. The remaining 14 trials used a combination of EPA and DHA. While only 4 (28%) met the defined endpoint, these trials with mixed O3FAs did not require statin use. <h3>Conclusions</h3> A meta-analysis of 19 CVD trials indicate that only IPE treatment was associated with reduced clinical events in statin-treated patients compared to mixed O3FAs. The basis for the distinct benefits of IPE are not fully understood but appear to be related to broad pleiotropic actions that correlate with on-treatment EPA levels. Elucidating such mechanisms for EPA will provide further insights into our understanding of CVD intervention.