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Review
. 2017 Sep 29;5(4):21.
doi: 10.3390/diseases5040021.

Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?

Theodosios D Filippatos  1 , Anastazia Kei  2 , Moses S Elisaf  3
Affiliations
Review

Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?

Theodosios D Filippatos et al. Diseases. .

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.

Keywords: anacetrapib; apolipoprotein; cardiovascular disease; cholesteryl ester transfer protein; diabetes.

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Conflict of interest statement

This review was conducted independently; no funding was received for writing this manuscript or for covering the costs to publish in open access. M.E. reports personal fees from Astra-Zeneca, grants and personal fees from Merck Sharp & Dohme, personal fees from Pfizer, Abbott, Sanofi-Aventis, Boehringer Ingelheim, Eli-Lilly and GlaxoSmithKline. A.K. and T.F. have given talks and attended conferences sponsored by various pharmaceutical companies, including Bristol-Myers Squibb, Pfizer, Lilly, Abbott, Amgen, AstraZeneca, Novartis, Vianex, Teva and Merck Sharp & Dohme.

Figures

Figure 1
Figure 1
Potential mechanisms of anacetrapib-mediated reduction of low-density lipoprotein (LDL) cholesterol. HDL: high-density lipoprotein, LDL: low-density lipoprotein, CETP: cholesteryl ester transfer protein, TRG: triglycerides, SREBP: sterol regulatory element binding protein, IDOL: inducible degrader of the low-density lipoprotein receptor, PCSK9: proprotein convertase subtilisin/kexin type 9.
Figure 2
Figure 2
Potential mechanisms of the anacetrapib-mediated reduction of triglycerides (TRG). PCSK9: proprotein convertase subtilisin/kexin type 9, CETP: cholesteryl ester transfer protein, Apo: apolipoprotein, LPL: lipoprotein lipase, VLDL: very low-density lipoprotein.
Figure 3
Figure 3
Potential mechanisms of anacetrapib-mediated changes of high-density lipoprotein (HDL) metabolism. CETP: cholesteryl ester transfer protein, Apo: apolipoprotein, TRG: triglycerides, ABCA1: ATP-binding cassette transporter ABCA1 (member 1 of human transporter sub-family ABCA).
See this image and copyright information in PMC

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