title: Torcetrapib/atorvastatin combination therapy.
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.
authors.affiliation: L-MARC Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. HBays@aol.com
authors.forename: Harold
authors.initials: H
authors.lastname: Bays
authors.forename: James
authors.initials: J
authors.lastname: McKenney
authors.forename: Michael
authors.initials: M
authors.lastname: Davidson
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; C483909:torcetrapib; D000069059:Atorvastatin