Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia
Date
2007
Authors
Kastelein J.J.P.
Van Leuven S.I.
Burgess L.
Evans G.W.
Kuivenhoven J.A.
Barter P.J.
Revkin J.H.
Grobbee D.E.
Riley W.A.
Shear C.L.
Journal Title
Journal ISSN
Volume Title
Publisher
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. Copyright © 2007 Massachusetts Medical Society.
Description
Keywords
acetylsalicylic acid, angiotensin receptor antagonist, atorvastatin, beta adrenergic receptor blocking agent, cholesterol, dipeptidyl carboxypeptidase inhibitor, ezetimibe, torcetrapib, cholesterol ester transfer protein, heptanoic acid derivative, high density lipoprotein cholesterol, hypocholesterolemic agent, low density lipoprotein cholesterol, pyrrole derivative, quinoline derivative, adult, article, atherosclerosis, blood pressure, carotid artery, carotid artery obstruction, cholesterol blood level, clinical trial, combination chemotherapy, controlled clinical trial, controlled study, dose response, double blind procedure, drug dose titration, drug effect, drug efficacy, familial hypercholesterolemia, female, heart infarction, human, ischemia, major clinical study, male, monotherapy, multicenter study, priority journal, randomized controlled trial, side effect, stroke, blood, carotid artery disease, disease course, drug antagonism, drug combination, echography, heterozygote, hyperlipoproteinemia type 2, middle aged, pathology, prospective study, Adult, Anticholesteremic Agents, Atherosclerosis, Carotid Arteries, Carotid Artery Diseases, Cholesterol Ester Transfer Proteins, Cholesterol, HDL, Cholesterol, LDL, Disease Progression, Double-Blind Method, Drug Therapy, Combination, Female, Heptanoic Acids, Heterozygote, Humans, Hyperlipoproteinemia Type II, Male, Middle Aged, Prospective Studies, Pyrroles, Quinolines
Citation
New England Journal of Medicine
356
16
356
16