Torcetrapib cuts postprandial VLDL-1 by 40 percent and reduces its atherogenic cholesteryl-ester content in type IIB hyperlipidemia (Arterioscler Thromb Vasc Biol 2008)

Original title: Inhibition of CETP by torcetrapib attenuates the atherogenicity of postprandial TG-rich lipoproteins in type IIB hyperlipidemia

Arterioscler Thromb Vasc Biol · 19 October 2007 · 6

Guerin M, Le Goff W, Duchene E, Julia Z, Nguyen T, Thuren T, Shear CL, Chapman MJ

This study evaluated the impact of torcetrapib on atherogenic triglyceride-rich lipoprotein subfractions after a meal in 18 patients with type IIB hyperlipidemia, comparing baseline, 6 weeks of atorvastatin 10 mg per day, and subsequently atorvastatin/torcetrapib 10/60 mg per day. On a background of atorvastatin, torcetrapib significantly reduced the postprandial area under the curve for VLDL-1 by 40% and VLDL-2 by 53%, with a smaller effect on chylomicrons (-24%), while the cholesteryl ester to triglyceride ratio in both VLDL-1 and VLDL-2 fell by 27% to 42%. This reduction stemmed from torcetrapib attenuating postprandial cholesteryl ester transfer to chylomicrons (-17%) and VLDL-1 (-33%), with the marked drop in postprandial VLDL-1 accompanied by apolipoprotein E enrichment, reflecting combined effects of torcetrapib on triglyceride-rich lipoprotein production, remodeling, and clearance.

Original abstract

Objective: The purpose of this study was to evaluate the impact of torcetrapib on atherogenic TG-rich lipoprotein subfractions in the postprandial phase in Type IIB hyperlipidemia.

Methods And Results: The quantitative and qualitative features of the postprandial profile of TG-rich lipoproteins were determined at baseline, after treatment for 6 weeks with 10 mg/d atorvastatin, and subsequently with an atorvastatin/torcetrapib combination (10/60 mg/d) in Type IIB patients (n=18). After ingestion of a standardized mixed meal, TG-rich lipoprotein subfractions were evaluated over 8 hours after each experimental period. On a background of atorvastatin, torcetrapib significantly attenuated the incremental postprandial area under the curve (iAUC 0 to 8 hours) for VLDL-1 (-40%), and the AUC 0 to 8 hours for VLDL-2 (-53%), with minor effect on chylomicron iAUC (-24%); concomitantly, the CE/TG ratio in both VLDL-1 and VLDL-2 was significantly reduced (-27% to -42%). Such reduction was attributable to torcetrapib-mediated attenuation of postprandial CE transfer to Chylomicrons (-17%) and VLDL-1 (-33%). Marked reduction in postprandial VLDL-1 levels was associated with apoE enrichment.

Conclusions: On a background of atorvastatin, torcetrapib attenuated the quantitative and qualitative features of the atherogenic postprandial profile of chylomicrons, VLDL-1 and VLDL-2. Such changes reflect the sum of torcetrapib-mediated effects on TG-rich lipoprotein production, intravascular remodeling, and catabolism.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.