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Previous Volume 356:1620-1630 April 19, 2007 Number 16 Next

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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] .)

Source Information

From the Academic Medical Center, University of Amsterdam, Amsterdam (J.J.P.K., S.I.L., J.A.K.); Tygerberg Hospital and Stellenbosch University, Tygerberg, South Africa (L.B.); Wake Forest University, Winston-Salem, NC (G.W.E., W.A.R.); the Heart Research Institute, Sydney (P.J.B.); Pfizer, New London, CT (J.H.R., C.L.S., W.T.D.); and the Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands (D.E.G., M.L.B.).

Drs. Kastelein and Bots contributed equally to this article.

This article (10.1056/NEJMoa071359) was published at www.nejm.org on March 26, 2007.

Address reprint requests to Dr. Kastelein at the Department of Vascular Medicine, Academic Medical Center, Meibergdreef 9, Room F4-159.2, 1105 AZ, Amsterdam, the Netherlands, or at j.j.kastelein{at}amc.uva.nl.

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