Anacetrapib
Anacetrapib, the new CETP inhibitor: raises large HDL2 and pre-beta HDL, lowers Lp(a) via ApoA production, and shows a hint of glucose benefit (Diseases 2017)
Original title: Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?
Three CETP inhibitors had already failed to reduce cardiovascular events in high-risk patients before this review examines anacetrapib. Anacetrapib substantially raises HDL cholesterol and apoA-I, with a marked rise in large HDL2 particles and pre-beta HDL particles, lowers LDL cholesterol mainly by increasing LDL receptor-mediated catabolism, lowers Lp(a) through decreased apo(a) production, and modestly lowers triglycerides via increased lipolysis and receptor-mediated catabolism of triglyceride-rich particles. The authors note anacetrapib may also benefit carbohydrate homeostasis. The REVEAL trial showed anacetrapib added to statin therapy significantly reduces cardiovascular events in atherosclerotic vascular disease patients without a significant increase in adverse events, despite its long half-life. The authors conclude anacetrapib could help manage dyslipidaemia in high-risk patients not reaching LDL-C targets or intolerant of statins, though its role in patients with elevated Lp(a) still needs to be established.
Original abstract
Cholesteryl ester transfer protein (CETP) inhibitors significantly increase serum high-density lipoprotein cholesterol (HDL) cholesterol levels and decrease low-density lipoprotein cholesterol (LDL) cholesterol concentration. However, three drugs of this class failed to show a decrease of cardiovascular events in high-risk patients. A new CETP inhibitor, anacetrapib, substantially increases HDL cholesterol and apolipoprotein (Apo) AI levels with a profound increase of large HDL2 particles, but also pre-β HDL particles, decreases LDL cholesterol levels mainly due to increased catabolism of LDL particles through LDL receptors, decreases lipoprotein a (Lp(a)) levels owing to a decreased Apo (a) production and, finally, decreases modestly triglyceride (TRG) levels due to increased lipolysis and increased receptor-mediated catabolism of TRG-rich particles. Interestingly, anacetrapib may be associated with a beneficial effect on carbohydrate homeostasis. Furthermore, the Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification (REVEAL) trial showed that anacetrapib administration on top of statin treatment significantly reduces cardiovascular events in patients with atherosclerotic vascular disease without any significant increase of adverse events despite its long half-life. Thus, anacetrapib could be useful for the effective management of dyslipidemias in high-risk patients that do not attain their LDL cholesterol target or are statin intolerable, while its role in patients with increased Lp(a) levels remains to be established.
anacetrapibdiabeteslipoprotein a
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.