Proposed mechanism of antioxidant activity of eicosapentaenoic acid (EPA) in Lp(a). Lp(a)-enriched lipoprotein fractions undergo more rapid lipid oxidation compared with other apolipoprotein B (ApoB)-containing lipoproteins, possibly due to oxidized phospholipids (oxPLs) attached to its unique apo(a) and in the phospholipid monolayer surrounding the insoluble lipid-rich core. The highly unsaturated fatty acid EPA exhibits significant dose- and time-dependent antioxidant activity in Lp(a). This action may arise from the five double bonds along the acyl chain allow for free radical resonance stabilization and may contribute to significant cardiovascular event reduction by highly purified EPA [delivered as icosapent ethyl (IPE)], particularly patients with elevated Lp(a) (REDUCE-IT).