The EPA/AA Ratio as a Residual Risk Marker in Statin-Treated Coronary Artery Disease Patients

This randomized trial enrolled 100 patients with established coronary artery disease on stable statin therapy and examined whether the EPA/AA ratio (eicosapentaenoic acid to arachidonic acid — a marker of omega-3 to omega-6 balance) was a significant predictor of residual cardiovascular risk after statin treatment, and whether EPA supplementation improved the ratio and associated biomarkers.

Patients with lower EPA/AA ratios at baseline had worse lipid profiles and higher inflammatory markers (hsCRP, oxidized LDL). EPA supplementation improved the EPA/AA ratio and reduced LDL-C and oxidized LDL, though the study was not powered for cardiovascular event outcomes.

The EPA/AA ratio has received more attention in Japanese cardiology than in Western guidelines, partly reflecting Japan’s higher baseline EPA/AA ratios from dietary fish intake. The JELIS trial (Yokoyama et al., 2007) demonstrated cardiovascular event reduction from EPA supplementation in Japanese patients, which contributed to EPA’s use as a residual risk marker in Japan.

The broader translational question — whether EPA/AA ratio modification meaningfully reduces cardiovascular events in Western populations on contemporary statin therapy — remains debated. The REDUCE-IT trial (Bhatt et al., 2019) showed icosapentaenoic acid (EPA) supplementation at high dose (4g/day) reduced MACE by 25%, but the mineral oil comparator’s LDL-raising effect complicated interpretation.

We rate the evidence limited. A small RCT providing mechanistic data on EPA/AA ratio as a statin-era residual risk marker — relevant context for omega-3 cardiovascular evidence but insufficient alone to guide clinical decisions.