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.
METHODS AND RESULTS
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.