title: Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia.
abstract: BACKGROUND
  Torcetrapib, an inhibitor of cholesteryl ester transfer protein, may reduce atherosclerotic vascular disease by increasing levels of high-density lipoprotein (HDL) cholesterol.
  
  
  METHODS
  A total of 850 patients with heterozygous familial hypercholesterolemia underwent B-mode ultrasonography at baseline and at follow-up to measure changes in carotid intima-media thickness. The patients completed an atorvastatin run-in period and were subsequently randomly assigned to receive either atorvastatin monotherapy or atorvastatin combined with 60 mg of torcetrapib for 2 years.
  
  
  RESULTS
  After 24 months, in the atorvastatin-only group, the mean (+/-SD) HDL cholesterol level was 52.4+/-13.5 mg per deciliter and the mean low-density lipoprotein (LDL) cholesterol level was 143.2+/-42.2 mg per deciliter, as compared with 81.5+/-22.6 mg per deciliter and 115.1+/-48.5 mg per deciliter, respectively, in the torcetrapib-atorvastatin group. During the study, average systolic blood pressure increased by 2.8 mm Hg in the torcetrapib-atorvastatin group, as compared with the atorvastatin-only group. The increase in maximum carotid intima-media thickness, the primary measure of efficacy, was 0.0053+/-0.0028 mm per year in the atorvastatin-only group and 0.0047+/-0.0028 mm per year in the torcetrapib-atorvastatin group (P=0.87). The secondary efficacy measure, annualized change in mean carotid intima-media thickness for the common carotid artery, indicated a decrease of 0.0014 mm per year in the atorvastatin-only group, as compared with an increase of 0.0038 mm per year in the torcetrapib-atorvastatin group (P=0.005).
  
  
  CONCLUSIONS
  In patients with familial hypercholesterolemia, the use of torcetrapib with atorvastatin, as compared with atorvastatin alone, did not result in further reduction of progression of atherosclerosis, as assessed by a combined measure of carotid arterial-wall thickness, and was associated with progression of disease in the common carotid segment. These effects occurred despite a large increase in HDL cholesterol levels and a substantial decrease in levels of LDL cholesterol and triglycerides. (ClinicalTrials.gov number, NCT00136981 [ClinicalTrials.gov].).
authors: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.j.kastelein@amc.uva.nl
authors: John J P
authors: JJ
authors: Kastelein
authors: Sander I
authors: SI
authors: van Leuven
authors: Leslie
authors: L
authors: Burgess
authors: Greg W
authors: GW
authors: Evans
authors: Jan A
authors: JA
authors: Kuivenhoven
authors: Philip J
authors: PJ
authors: Barter
authors: James H
authors: JH
authors: Revkin
authors: Diederick E
authors: DE
authors: Grobbee
authors: Ward A
authors: WA
authors: Riley
authors: Charles L
authors: CL
authors: Shear
authors: William T
authors: WT
authors: Duggan
authors: Michiel L
authors: ML
authors: Bots
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D011804:Quinolines; C483909:torcetrapib; D000069059:Atorvastatin