Eicosapentaenoic Acid Combined with Optimal Statin Therapy Improves Endothelial Dysfunction in Patients with Coronary Artery Disease

Purpose Eicosapentaenoic acid (EPA) has been reported to augment endothelial function and improve clinical outcomes in patients with coronary artery disease (CAD). The purpose of this study was to determine whether EPA could improve residual endothelial dysfunction despite adequate lipid-lowering with statin in CAD patients. Eighty patients with established CAD, who had been on statin treatment and had serum low-density lipoprotein cholesterol (LDL-C) levels < 100 mg/dl, were randomly assigned to receive either 1,800 mg of EPA daily plus statin (EPA group, n = 40) or statin alone (Control group, n = 40). Lipid profiles and flow-mediated dilation (FMD) were assessed just before and after more than 3 months of treatment in both groups. Only patients who had impaired FMD (< 6 %) before randomization were enrolled. After treatment for 5.2 +/- 1.7 months, the EPA group showed a significant increase in the serum concentration of EPA and EPA to arachidonic acid (AA) (EPA/AA) ratio (62.5 +/- 38.1 to 159.8 +/- 53.8 mu g/ml, 0.45 +/- 0.34 to 1.20 +/- 0.55, p < 0.01 for both). In the EPA group, serum triglycerides significantly decreased (150.7 +/- 92.9 to 119.3 +/- 60.7 mg/dl, p = 0.02), whereas no significant change was seen in the Control group. FMD, the primary study endpoint, showed a significant improvement in the EPA group (2.6 +/- 1.6 % to 3.2 +/- 1.6 %, p = 0.02), whereas no significant change was observed in the Control group (2.7 +/- 1.6 % to 2.4 +/- 1.7 %, p = 0.29). EPA improved endothelial function and impaired FMD in patients with established CAD who were on optimal statin therapy.