Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia

N Engl J Med. 2007 Apr 19;356(16):1620-30. doi: 10.1056/NEJMoa071359. Epub 2007 Mar 26.

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].).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology
  • Atorvastatin
  • Carotid Arteries / drug effects
  • Carotid Arteries / pathology
  • Carotid Artery Diseases / drug therapy*
  • Carotid Artery Diseases / etiology
  • Carotid Artery Diseases / pathology
  • Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Heptanoic Acids / therapeutic use*
  • Heterozygote
  • Humans
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / complications
  • Hyperlipoproteinemia Type II / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyrroles / therapeutic use*
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*

Substances

  • Anticholesteremic Agents
  • Cholesterol Ester Transfer Proteins
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Heptanoic Acids
  • Pyrroles
  • Quinolines
  • torcetrapib
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00136981