A review of torcetrapib/atorvastatin combination therapy covers the chemistry, mechanism, and pharmacokinetics behind their complementary lipid effects (Expert Rev Cardiovasc Ther 2005)

Original title: Torcetrapib/atorvastatin combination therapy

Expert Rev Cardiovasc Ther · 1 September 2005 · 5

Bays H, McKenney J, Davidson M

This review examines the combination of atorvastatin, which primarily lowers LDL cholesterol by inhibiting HMG-CoA reductase and has been shown to reduce coronary heart disease events, with torcetrapib, a CETP inhibitor that primarily raises HDL cholesterol and has generally shown reduced atherosclerosis in rabbit studies. Since statin monotherapy reduces coronary heart disease risk in only a minority of patients relative to placebo, and low HDL cholesterol independently predicts coronary heart disease risk, the authors argue that torcetrapib and atorvastatin together provide striking, complementary improvements across key lipid parameters. The review covers the chemistry, mechanism of action, pharmacokinetics, metabolism, safety and tolerability, and efficacy of the combination, then in development, as a strategy for reducing coronary heart disease risk beyond atorvastatin alone.

Original abstract

Elevated blood levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk for atherosclerotic coronary heart disease (CHD). Atorvastatin is a statin drug that inhibits 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (the rate-limiting step of cholesterol production) and primarily lowers LDL-C levels. Atorvastatin has also been shown to significantly reduce CHD events. However, as with all statins (and all other monotherapy lipid-altering drugs), atorvastatin alone reduces the risk of CHD in only a minority of patients relative to placebo. Conversely, it is low levels of high-density lipoprotein cholesterol that are associated with increased CHD risk. Torcetrapib is a cholesteryl ester transfer protein inhibitor that primarily raises high-density lipoprotein cholesterol levels, and cholesteryl ester transfer protein inhibition has generally been shown to reduce atherosclerosis in rabbits. Taken together, atorvastatin and torcetrapib provide striking improvements in lipid levels, and complementary actions upon important lipid parameters. This review examines the chemistry, mechanism of action, pharmacokinetics, metabolism, safety/tolerability and efficacy of the combination torcetrapib/atorvastatin agent that is currently in development and that provides complementary lipid benefits towards the goal of reducing CHD risk beyond that of atorvastatin alone.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.