Abstract 16398: Effect of CETP Inhibition With Anacetrapib on VLDL Triglyceride and Plasma ApoC-II, ApoC-III and ApoE Metabolism

Background: CETP inhibition with anacetrapib reduces triglyceride (TG) and cholesteryl ester transfer among lipoproteins and increases very low density lipoprotein (VLDL) apolipoprotein B (apoB) clearance. This study reports the effects of anacetrapib on VLDL-TG, apoC-II, apoC-III and apoE metabolism. Methods: Mildly hypercholesterolemic subjects were randomized to background placebo (N=10) or atorvastatin 20 mg (N=29) for 4 weeks, followed by addition of anacetrapib 100 mg for another 8-weeks. Subjects underwent stable isotope kinetic studies to determine fractional catabolic rates (FCR) and production rates (PR) of VLDL-TG, apoC-II, C-III and E. Results: Anacetrapib reduced the circulating VLDL-TG pool by 14% (p=.006) in subjects on atorvastatin due to an increase in FCR (29%; p=.002) without changing plasma TG. VLDL-TG pool size did not change in the anacetrapib monotherapy group; although FCR increased by 40% (p=.11), these changes were offset by a 39% increase in PR (p=.01), which was not observed in...