Abstract 14954: 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 >885 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 <-10% in apoC3-T2&T3. OO-adjusted PCHG in TG by OM3-CA was -10% to -28% in the two high apoC3 tertiles (T2&3), and -5% in apoC3 lowest tertile. In the two high apoC3 tertiles (T2&T3), non-HDL-C reductions were absent with OO but OM3-CA caused a consistent non-HDL-C PCGH of -11%. Olive oil-adjusted PCHG in VLDL-C by OM3-CA was -7% to -21% in the high apoC3 tertiles (T2&3), and -3% in the lowest apoC3 tertile. Increments in LDL-c were numerically greater with Epanova than OO but not different across apoC3 tertiles. A statistically significant association for PCHG between TG and apoC3 was found with OO (r=0.34; p=0.002) but not with OM3-CA (r=0.15; p=0.19).
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.
Author Disclosures: E.S. Stroes: None. A.V. Susekov: Research Grant; Modest; AstraZeneca. Other Research Support; Modest; KRKA, Sanofi, Amgen. Other Research Support; Significant; AstraZeneca. Speakers Bureau; Modest; Pfizer, Sanofi, Teva, Amgen. Speakers Bureau; Significant; AstraZeneca, KRKA. Honoraria; Modest; Sanofi, Teva, Amgen. Honoraria; Significant; AstraZeneca, KRKA. Expert Witness; Modest; Pfizer. Expert Witness; Significant; AstraZeneca, Sanofi, Teva, Amgen. Consultant/Advisory Board; Modest; Pfizer, Amgen. Consultant/Advisory Board; Significant; AstraZeneca, Sanofi, Teva. H. Yang: Employment; Significant; AstraZeneca LP. M. Kvarnström: Employment; Significant; AstraZeneca LP. T.W. de Bruin: Employment; Significant; AstraZeneca LP. S.C. Carlsson: Employment; Significant; AstraZeneca LP. M.H. Davidson: Employment; Significant; Corvidia Therapeutics. Speakers Bureau; Significant; AMGEN, Regeneron, Sanofi. Consultant/Advisory Board; Modest; AstraZeneca. Consultant/Advisory Board; Significant; AMGEN, Regeneron, Sanofi.
- © 2016 by American Heart Association, Inc.