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.