Anacetrapib
Anacetrapib dose-dependently shrinks atherosclerotic lesions by up to 92% and adds to the benefit of atorvastatin (Eur Heart J 2015)
Original title: Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin
APOE*3Leiden.CETP mice were fed a diet with ascending anacetrapib doses (0.03, 0.3, 3, or 30 mg/kg/day), atorvastatin 2.4 mg/kg/day alone, or atorvastatin combined with anacetrapib 0.3 mg/kg/day, for 21 weeks. Anacetrapib dose-dependently reduced CETP activity (-59 to -100%, P less than 0.001), decreasing non-HDL-C (-24 to -45%) and increasing HDL-C (+30 to +86%, both P less than 0.001). Atherosclerotic lesion area fell dose-dependently by -41 to -92% (P less than 0.01), lesion severity decreased, and plaque stability index rose; combining anacetrapib with atorvastatin further reduced lesion size by -95% (P less than 0.001). Analysis of covariance showed both anacetrapib itself (P less than 0.05) and non-HDL-C (P less than 0.001), but not HDL-C (P equals 0.76), independently predicted lesion size, indicating the anti-atherogenic effect of anacetrapib and its additive benefit with atorvastatin are driven mainly by lowering non-HDL-C rather than raising HDL-C.
Original abstract
Background: The residual risk that remains after statin treatment supports the addition of other LDL-C-lowering agents and has stimulated the search for secondary treatment targets. Epidemiological studies propose HDL-C as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to atherogenic (V)LDL. The CETP inhibitor anacetrapib decreases (V)LDL-C by ∼15-40% and increases HDL-C by ∼40-140% in clinical trials. We evaluated the effects of a broad dose range of anacetrapib on atherosclerosis and HDL function, and examined possible additive/synergistic effects of anacetrapib on top of atorvastatin in APOE*3Leiden.CETP mice.
Methods And Results: Mice were fed a diet without or with ascending dosages of anacetrapib (0.03; 0.3; 3; 30 mg/kg/day), atorvastatin (2.4 mg/kg/day) alone or in combination with anacetrapib (0.3 mg/kg/day) for 21 weeks. Anacetrapib dose-dependently reduced CETP activity (-59 to -100%, P < 0.001), thereby decreasing non-HDL-C (-24 to -45%, P < 0.001) and increasing HDL-C (+30 to +86%, P < 0.001). Anacetrapib dose-dependently reduced the atherosclerotic lesion area (-41 to -92%, P < 0.01) and severity, increased plaque stability index and added to the effects of atorvastatin by further decreasing lesion size (-95%, P < 0.001) and severity. Analysis of covariance showed that both anacetrapib (P < 0.05) and non-HDL-C (P < 0.001), but not HDL-C (P = 0.76), independently determined lesion size.
Conclusion: Anacetrapib dose-dependently reduces atherosclerosis, and adds to the anti-atherogenic effects of atorvastatin, which is mainly ascribed to a reduction in non-HDL-C. In addition, anacetrapib improves lesion stability.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.