Abstract 17223: Compositional Lipoprotein Changes With Omega-3 Carboxylic Acids in Patients With Hypertriglyceridemia Paired With Low HDL-C: A Substudy From the ESPRIT Trial

Abstract

Introduction: STRENGTH (NCT02104817) is a 13,000-patient cardiovascular (CV) outcomes trial testing the hypothesis that high-CV-risk patients on statins with hypertriglyceridemia paired with low levels of high-density lipoprotein cholesterol (HDL-C) will have a reduction in incidence of major adverse CV events with omega-3 carboxylic acids (OM3-CA) 4 g/day compared with corn oil control. At present, the triglyceride (TG)-lowering mechanisms by which OM3-CA therapy may reduce CV risk are uncertain. Methods: In the ESPRIT trial (NCT01408303), patients (n=277) on statins who had fasting TG ≥200 mg/dL and <500 mg/dL and HDL-C <40 mg/dL for men and <45 mg/dL for women (also STRENGTH inclusion criteria) received either OM3-CA 4 g/day or olive oil (OO) 4 g/day for 6 weeks. The primary efficacy end point was percentage change in non-HDL-C from baseline to 6 weeks. We evaluated the lipoprotein compositional changes associated with non-HDL-C reduction. Results: Least-squares mean difference in HDL2:HDL3 ratio increased by 12% (p=0.004), while apolipoprotein (Apo)B100, ApoB48 and PCSK9 were not significantly affected. The sum of the change in the highly atherogenic subfractions, very-low-density lipoprotein cholesterol (VLDL-C) + small LDL-C + remnant lipoprotein-C, was strongly correlated with TG reduction (0.732; p<0.001) and percentage change in plasma eicosapentaenoic acid + docosahexaenoic acid + docosapentaenoic acid (–0.281; p<0.001). Conclusions: Compared with OO, OM3-CA 4 g/day significantly lowers non-HDL-C in patients with hypertriglyceridemia and low HDL-C by lowering VLDL-C, small LDL-C and remnant lipoprotein-C. Large LDL-C is raised without modifying ApoB100, ApoB48 or PCSK9 levels. STRENGTH will determine whether these lipoprotein compositional changes in this high-risk population will result in a CV benefit.