Canadian Journal of Cardiology


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      Cardiovascular disease (CVD) is the primary cause of mortality worldwide. Ischemic events associated with CVD are causatively related to vascular inflammation and atherothrombosis. Certain omega-3 fatty acids, such as eicosapentaenoic acid (EPA), are thought to have anti-inflammatory and anti-thrombotic properties. Icosapent ethyl (IPE) is an ethyl ester of EPA, currently approved by Health Canada as prescription IPE. At 4 g/d, IPE significantly reduced clinical events in high-risk patients with diabetes and other risk factors of CV disease in the REDUCE-IT trial. Previous clinical trials, with the majority of them administering a combination of EPA and the O3FA, docosahexaenoic acid (DHA), have been conducted with mixed outcomes. This study aimed to determine whether O3FA formulations of EPA alone versus mixed combinations can confer protection in patients with CVD.


      The meta-analysis included 13 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 included 4 clinical trials that assessed the effect of omega-3 fatty acids on coronary plaque volume and stability. All trials involved formulations with EPA alone or in combination with DHA. Out of 17 trials using omega-3 fatty acids in patients with CVD risk, 5 employed EPA alone, all of which (100%) met the defined endpoints. The remaining 12 trials used a combination of EPA and DHA, of which only 4 (33%) met the defined endpoints, but only in patients where statin use was not prespecified. The differences in outcomes did not correlate with triglyceride lowering.


      In a meta-analysis of O3FA trials, the formulation of EPA alone as icosapent ethyl (IPE) was superior to mixtures containing DHA in statin-treated patients. The benefits with IPE are attributed to potential anti-inflammatory, anti-oxidant and anti-thrombotic actions. Elucidating such mechanisms for EPA will lead to further insights into our understanding of atherosclerosis and strategies for CVD treatment.
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