Abstract 12252: Effects of the Cholesteryl Ester Transfer Protein Inhibitor, Evacetrapib, Administered as Monotherapy or in Combination With Statins on Cholesterol Efflux and HDL Particles in Patients With Dyslipidemia
Objectives: The CETP inhibitor evacetrapib (EVA) has been shown to substantially increase HDL-C and apoA-I levels as monotherapy and combined with statins. The effects of EVA on cholesterol efflux capacity and HDL particle distribution have not been described and were evaluated in this study.
Methods: Samples from patients (n=398) with elevated LDL-C or low HDL-C enrolled in the multicenter, randomized, double-blind, parallel, placebo-controlled trial (JAMA 2011;306:2099-2109, NCT01105975) were studied. Percent changes from baseline in cholesterol efflux capacity (global, ABCA1- and non-ABCA1-mediated), preβ HDL (measured by immunofixation and 2D-gel), and other HDL subclasses (measured by 2D-gel and NMR) were evaluated after 12 weeks of placebo (PBO), statins alone, EVA alone, and EVA with statins.
Results: Results are shown in the table. Statins alone decreased global and ABCA1-mediated cholesterol efflux and preβ-1 HDL (by 2D-gel). EVA alone and combined with statins increased global (28% and 21%, respectively), ABCA1- (17% and 15%, respectively), and non-ABCA1-mediated (35% and 27%, respectively) cholesterol efflux. EVA alone increased preβ-1 as measured by 2D-gel (20%) and immunofixation (32%); EVA combined with statins increased preβ-1 as measured by 2D-gel (27%). While statins alone had no significant effect on large and very large HDL (α-1 and α-2 HDL by 2D-gel, and large HDL by NMR), EVA alone and combined with statins increased these more buoyant HDL particles. Statins alone and EVA alone had no effect on small HDL, whereas EVA combined with statins significantly decreased small HDL particles as measured by NMR.
Conclusion: In subjects with elevated LDL-C or low HDL-C, EVA alone and combined with statins increased global, ABCA1- and non-ABCA1-mediated cholesterol efflux. This improved global cholesterol efflux capacity was accompanied by a significant increase in preβ-1 and large and very large HDL particles.
Author Disclosures: D.J. Rader: None. G. Ruotolo: Employment; Significant; Eli Lilly and Company. J.P. Kane: None. M. Wang: Employment; Significant; Eli Lilly and Company. K.A. Krueger: Employment; Significant; Eli Lilly and Company. S.E. Nissen: Other Research Support; Significant; AstraZeneca, Amgen, Eli Lilly and Company, Pfizer, The Medicines Company, Novartis, Takeda, Orexigen, Vivus. S.J. Nicholls: Other Research Support; Significant; Eli Lilly and Company. Consultant/Advisory Board; Significant; Eli Lilly and Company. B.H. Brewer: None.
- © 2014 by American Heart Association, Inc.