Anacetrapib
Dalcetrapib and anacetrapib generate large apoE-containing HDL particles that can bind the hepatic LDL receptor (J Lipid Res 2023)
Original title: Dalcetrapib and anacetrapib increase apolipoprotein E-containing HDL in rabbits and humans
In New Zealand White rabbits on atorvastatin, dalcetrapib and anacetrapib each raised HDL cholesterol by more than 58% (P less than 0.01) and increased large apoE-containing HDL by 66% (P less than 0.001) and 59% (P less than 0.01) respectively; HDL from these CETP-inhibitor-treated rabbits competed with human LDL for binding to the LDL receptor on HepG2 cells more strongly than control HDL (P less than 0.01). In a subset of patients from the dal-PLAQUE-2 study, dalcetrapib increased large HDL particle concentration by 69% (P less than 0.001) and apoB-depleted plasma apoE by 24% (P less than 0.001), producing apoE-containing HDL devoid of apoA-I (plus 47%, P less than 0.001). Across both species, CETP inhibitors increased large apoE-containing HDL that can interact with the hepatic LDL receptor, suggesting the catabolism of these particles, and their contribution to reverse cholesterol transport, depends on adequate LDL receptor availability.
Original abstract
The large HDL particles generated by administration of cholesteryl ester transfer protein inhibitors (CETPi) remain poorly characterized, despite their potential importance in the routing of cholesterol to the liver for excretion, which is the last step of the reverse cholesterol transport. Thus, the effects of the CETPi dalcetrapib and anacetrapib on HDL particle composition were studied in rabbits and humans. The association of rabbit HDL to the LDL receptor (LDLr) in vitro was also evaluated. New Zealand White rabbits receiving atorvastatin were treated with dalcetrapib or anacetrapib. A subset of patients from the dal-PLAQUE-2 study treated with dalcetrapib or placebo were also studied. In rabbits, dalcetrapib and anacetrapib increased HDL-C by more than 58% (P < 0.01) and in turn raised large apo E-containing HDL by 66% (P < 0.001) and 59% (P < 0.01), respectively. Additionally, HDL from CETPi-treated rabbits competed with human LDL for binding to the LDLr on HepG2 cells more than control HDL (P < 0.01). In humans, dalcetrapib increased concentrations of large HDL particles (+69%, P < 0.001) and apo B-depleted plasma apo E (+24%, P < 0.001), leading to the formation of apo E-containing HDL (+47%, P < 0.001) devoid of apo A-I. Overall, in rabbits and humans, CETPi increased large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport.
anacetrapibdalcetrapibHDL biologymechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.