VRN

Background  Torcetrapib, an inhibitor of cholesteryl ester transfer protein, may reduce atheroscle- rotic vascular disease by increasing levels of high-density lipoprotein (HDL) choles- terol. Methods A total of 850 patients with heterozygous familial hypercholesterolemia underwent B-mode ultrasonography at baseline and at follow-up to measure changes in ca- rotid intima–media thickness. The patients completed an atorvastatin run-in period and were subsequently randomly assigned to receive either atorvastatin monother- apy 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–atorva- statin 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 pri- mary 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 in- tima–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). Copyright © 2007 Massachusetts Medical Society. Conclusions In patients with familial hypercholesterolemia, the use of torcetrapib with atorva- statin, as compared with atorvastatin alone, did not result in further reduction of progression of atherosclerosis, as assessed by a combined measure of carotid arte- rial-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.