Effect of Torcetrapib on Carotid Atherosclerosis in Familial Hypercholesterolemia

• Published in: The New England journal of medicine Vol. 356; no. 16; pp. 1620 - 1630
• Main Authors: Kastelein, John J.P, van Leuven, Sander I, Burgess, Leslie, Evans, Greg W, Kuivenhoven, Jan A, Barter, Philip J, Revkin, James H, Grobbee, Diederick E, Riley, Ward A, Shear, Charles L, Duggan, William T, Bots, Michiel L
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 19.04.2007
• Subjects: Adult; Anticholesteremic Agents - pharmacology; Anticholesteremic Agents - therapeutic use; Apolipoproteins; Atherosclerosis (general aspects, experimental research); Atherosclerosis - drug therapy; Atherosclerosis - etiology; Atherosclerosis - pathology; Atorvastatin Calcium; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular disease; Carotid Arteries - drug effects; Carotid Arteries - pathology; Carotid Artery Diseases - drug therapy; Carotid Artery Diseases - etiology; Carotid Artery Diseases - pathology; Cholesterol; Cholesterol Ester Transfer Proteins - antagonists & inhibitors; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Diet; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; General aspects; Heptanoic Acids - therapeutic use; Heterozygote; Humans; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - complications; Hyperlipoproteinemia Type II - drug therapy; Male; Medical sciences; Middle Aged; Prospective Studies; Pyrroles - therapeutic use; Quinolines - pharmacology; Quinolines - therapeutic use; Cardiovascular disease; Metabolic diseases; Lipids; Hyperlipoproteinemia; Lipoprotein; Cholesterol; Genetic disease; Vascular disease; Medicine; Hypercholesterolemia; Torcetrapib; Carotid; Atherosclerosis; Dyslipemia; Antilipemic agent
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa071359

Since torcetrapib, an inhibitor of cholesteryl ester transfer protein, markedly increases levels of high-density lipoprotein cholesterol and lowers levels of low-density lipoprotein cholesterol, in principle it might have a beneficial effect on atherosclerosis. However, in this clinical trial, torcetrapib had no beneficial effect on carotid atherosclerosis, as assessed by ultrasonographic measurement of carotid intima–media thickness. The reasons for this finding are unclear, but the drug did increase blood pressure slightly. In this clinical trial, torcetrapib had no beneficial effect on carotid atherosclerosis, as assessed by ultrasonographic measurement of carotid intima–media thickness.Published Online March 26, 2007 (DOI:10.1056/NEJMoa071359) Guidelines for the prevention and management of cardiovascular disease focus on reducing levels of low-density lipoprotein (LDL) cholesterol by means of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (collectively referred to as statins). 1 , 2 However, recent meta-analyses have shown that even with the most aggressive treatment, 3 , 4 these drugs reduce the risk of a major coronary event by only 30%. 5 This finding, combined with an estimation that mortality from cardiovascular causes will increase worldwide by 90% by the year 2020, as compared with that in 1990, 6 illustrates the need for new efficacious treatments. A review of four large, prospective epidemiologic studies . . .