Anacetrapib for the treatment of dyslipidaemia: the last bastion of the cholesteryl ester transfer protein inhibitors?

ABSTRACT

Introduction: Inhibition of cholesteryl ester transfer protein (CETP) has emerged as a potential way to decrease cardiovascular risk by raising high density lipoprotein (HDL) cholesterol and lowering low density lipoprotein (LDL) cholesterol concentrations. However, high profile withdrawals of several CETP inhibitors have cast doubt over this hypothesis. Despite this concern, anacetrapib appears to be safe, well-tolerated and delivers a substantial increases in HDL cholesterol and reductions in LDL cholesterol as monotherapy and when combined with a statin.

Areas covered: We discuss the role of CETP and HDL cholesterol as therapeutic targets, describe the pharmacokinetics and pharmacodynamics of anacetrapib, as well as report on the recent clinical trials.

Expert opinion: The focus of CETP inhibition has shifted from HDL cholesterol-raising to LDL cholesterol-lowering. Although anacetrapib appears to be safe and is effective in altering lipid-related biochemical parameters of interest, its effect on cardiovascular outcomes remains unknown. Extrapolation of LDL cholesterol lowering to improved cardiovascular outcomes is not possible, because LDL and HDL functionality in the setting of anacetrapib treatment is unclear. The results of the phase III REVEAL randomised controlled trial will be critical for anacetrapib to establish a place in clinical care.

KEYWORDS:

• Anacetrapib
• apolipoprotein A-I
• atherosclerosis
• cardiovascular disease
• cholesteryl ester transfer protein inhibitors
• high density lipoprotein
• low density lipoprotein

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

ORCID

Michael M Page http://orcid.org/0000-0002-3593-2073

John R Burnett http://orcid.org/0000-0002-0135-6119