Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive
statin therapy, underscoring the need for additional intervention.
Eicosapentaenoic acid (EPA), an omega-3
polyunsaturated fatty acid, is incorporated into membrane
phospholipids and
atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through
rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation,
inflammation, plaque formation/progression, platelet aggregation,
thrombus formation, and plaque
rupture. EPA also improves atherogenic
dyslipidemia characterized by reduction of
triglycerides without raising
low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of
statins when given as adjunctive
therapy. In this review, we present data supporting the
biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl
ester of EPA (
icosapent ethyl) at 4 g/day combined with
statin therapy is superior to
statin therapy alone for reducing CV events in high-risk patients with mixed
dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive
therapy to a
statin for reduction of residual CV risk.