Baseline Apolipoprotein C-III Predicts Triglyceride Lowering by Omega-3 Carboxylic Acids in Patients With Severe Hypertriglyceridemia

Introduction: High apoC3 inhibits the clearance of triglyceride (TG)-rich lipoproteins and is associated with cardiovascular disease. The EVOLVE I trial (NCT01242527) demonstrated that apolipoprotein C3 (apoC3) predicts TG and non-HDL-C reductions in severe hypertriglyceridemia (HTG) treated with omega-3 carboxylic acids (OM3-CA; Epanova) 4 g/d. In EVOLVE II (NCT02009865), OM3-CA 2 g/d lowered TG vs. olive oil (OO) placebo in severe HTG (p=0.017) and in the co-primary TG u003e885 mg/dl subgroup (p=0.0008). Aim: An analysis was conducted on EVOLVE II data whether efficacy of the 2g dose of OM3-CA is predicted by baseline apoC3. Methods: Treatment specific median %-change from BL (PCHG) and adjusted least square means (LSM) differences from ANCOVA on log transformed lipid values, with log-baseline value and statin use as covariates, were compared per apoC3 tertile. Associations between TG and apoC3 PCHG were examined by Pearson Correlation r. Results: In EVOLVE II, the OM3-CA induced PCHG in TG was -25% to -30% across apoC3 tertiles; OO caused PCHG in TG of -8% in the lowest apoC3 tertile and Conclusion: In patients with severe hypertriglyceridemia treated with OM3-CA 2g/d or OO 2g/d, baseline apoC3 levels are a predictor of lipid modifying efficacy. The data indicate that higher apoC3 levels are a useful biomarker to select patients more likely to respond to omega-3 prescription therapy.