The RADIANCE 1 trial finds torcetrapib worsens common carotid thickening in familial hypercholesterolemia despite raising HDL to 81.5 mg per dL (N Engl J Med 2007)

Original title: Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia

N Engl J Med · 26 March 2007 · 8

Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, Revkin JH, Grobbee DE, Riley WA, Shear CL, Duggan WT, Bots ML et al.

In 850 patients with heterozygous familial hypercholesterolemia, researchers tested whether torcetrapib could slow carotid atherosclerosis after an atorvastatin run-in period, randomizing patients to atorvastatin monotherapy or atorvastatin plus torcetrapib 60 mg for 2 years. After 24 months, the torcetrapib-atorvastatin group reached HDL cholesterol of 81.5 mg per dL and LDL cholesterol of 115.1 mg per dL, versus 52.4 and 143.2 mg per dL with atorvastatin alone, but systolic blood pressure rose 2.8 mmHg more with torcetrapib. The primary efficacy measure, maximum carotid intima-media thickness increase, was similar between groups (0.0047 versus 0.0053 mm per year, p = 0.87), while the secondary measure for the common carotid artery showed progression with torcetrapib (+0.0038 mm per year) versus regression with atorvastatin alone (-0.0014 mm per year, p = 0.005), showing torcetrapib failed to slow atherosclerosis progression and was linked to disease progression in the common carotid segment despite substantially improved lipids.

Original 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].).

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.