Abstract 19030: Apolipoprotein C-III is Significantly Reduced by Prescription Omega-3 Free Fatty Acids (Epanova) in Patients with Severe Hypertriglyceridemia and Changes Correlate with Increases in LDL-C: A Sub-analysis of the EVOLVE trial

Abstract

Background: Apolipoprotein C-III (apoC-III) inhibits lipoprotein lipase activity and hepatic uptake of triglyceride-rich lipoproteins. Elevated levels of apoC-III have been found to be an independent predictor for CHD risk and genetically reduced apoC-III is associated with protection from CHD, making apoC-III a therapeutic target. Omega-3 fatty acid formulations containing docosahexaenoic acid (DHA) have been shown to increase LDL-C in patients with severe hypertriglyceridemia (HTG). Clinical data suggest that eicosapentaenoic acid (EPA) alone, which lowers triglycerides to a similar extent as EPA + DHA, does not raise LDL-C, but also fails to lower apoC-III. Materials: The EVOLVE trial evaluated 2, 3, and 4 g/d of a novel omega-3 free-fatty acid (FFA) formulation containing both EPA + DHA compared with 4 g/d of olive oil. In 399 patients with severe HTG we evaluated the effects on plasma apoC-III levels and the correlations between change in apoC-III and change in plasma lipids (TG, LDL-C) after 12-weeks of therapy. Results: Epanova 2, 3, and 4 g/d produced significant median reductions in apoC-III by 9 (p=0.02), 13 (p=0.006), and 15% (p<0.001), respectively, compared to olive oil (+5%). Epanova produced significant (p<0.001) median reductions in triglycerides (TG) of 26, 22, and 31%, respectively, compared to 10% for olive oil, and significant (p<0.001) median increases in LDL-C of 21, 16, 26%, respectively, compared to 10% for olive oil. There was a significant positive correlation between percent changes in apoC-III and triglycerides (r=0.603, p<0.001) and a significant negative correlation between percent changes in apoC-III and LDL-C concentrations (r=-0.28, p<0.001). Conclusion: A novel omega-3 FFA formulation containing both EPA and DHA significantly lowered apoC-III levels in addition to reducing TG levels. An increase in LDL-C correlated with the reduction in apoC-III. Since EPA alone does not appear to lower apoC-III, these results support the hypothesis that DHA has specific effects in lowering apoC-III and that the mechanism by which DHA increases LDL-C may be related to its effect to lower apo CIII.