Rating Atherosclerotic Disease Change by Imaging With a New CETP Inhibitor - RADIANCE 1 – Presented at ACC 2007


The goal of the trial was to evaluate the effect of treatment with torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, in addition to atorvastatin compared with atorvastatin alone on disease progression among patients with heterozygous familial hypercholesterolemia.

Study Design

Study Design:

Patients Enrolled: 904
Mean Follow Up: 24 months
Mean Patient Age: Mean age, 46 years
Female: 51

Patient Populations:

Heterozygous familial hypercholesterolemia and eligible for statin treatment, as per NCEP Adult Treatment Panel III

Primary Endpoints:

Annualized rate of change in maximum IMT for 12 carotid segments

Secondary Endpoints:

Maximum CIMT for each site; mean CIMT common carotid

Drug/Procedures Used:

Following a 6- to 14-week run-in phase in which all patients were treated with atorvastatin titrated to achieve National Cholesterol Education Program (NCEP) recommended low-density lipoprotein (LDL) levels, patients were randomized in a double-blind manner to treatment with torcetrapib (60 mg; n = 450) in addition to atorvastatin compared with atorvastatin alone with matching placebo (n = 454). Carotid ultrasound was performed at randomization and every 6 months for 24 months.

Principal Findings:

Baseline lipid means were high-density lipoprotein (HDL) of 52 mg/dl, LDL of 138 mg/dl, total cholesterol of 213 mg/dl, and triglycerides of 97 mg/dl. Average dose of atorvastatin used in the study was 56.5 mg.

At study end, HDL cholesterol was significantly increased from baseline in the torcetrapib group to 81.5 mg/dl, but stayed at 52 mg/dl in the atorvastatin monotherapy group (p < 0.001 for between-group comparison). Likewise, LDL reductions were greater with torcetrapib than atorvastatin monotherapy (final LDL 115.1 mg/dl vs. 143.2 mg/dl, p < 0.001). All other final lipid parameters also favored the torcetrapib group.

There was no difference in the primary endpoint of annualized rate of change in maximum carotid intima-media thickness (CIMT) for 12 carotid segments between treatment groups (0.0053 mm/year for the torcetrapib group vs. 0.0047 mm/year for atorvastatin monotherapy, p = 0.87). Change in maximum CIMT for each of the four common carotid-artery sites showed progression in the torcetrapib group and regression in the atorvastatin monotherapy group (0.0040 mm/year vs. -0.0042 mm/year, p = 0.02 between groups), as did change in mean CIMT for each of the four common carotid artery sites (0.0038 mm/year vs. -0.0014 mm/year, p = 0.005 between groups).

Serious adverse events occurred more frequently in the torcetrapib group (12.4% vs. 8.6%), as did serious cardiovascular events (5.3% vs. 2.4%). Final systolic blood pressure was 2.8 mm Hg higher in the torcetrapib group than the atorvastatin monotherapy group (121.7 mm Hg vs. 119.0 mm Hg).


Among patients with heterozygous familial hypercholesterolemia, treatment with the CETP inhibitor torcetrapib in addition to atorvastatin was not associated with a reduction in disease progression or regression compared with atorvastatin alone through 2 years of treatment.

Despite a marked increase in HDL cholesterol and reduction in LDL cholesterol during the study, torcetrapib was not associated with regression of atherosclerotic disease and was actually shown to have worsening disease progression compared with atorvastatin monotherapy for the secondary endpoints of maximum CIMT and mean CIMT in the common carotid. These findings add to the growing body of pathophysiologic information surrounding torcetrapib. However, none of the data presented so far provide a clear-cut explanation for the increase in mortality that was reported in the large outcomes trial with torcetrapib. Full results of the outcomes trial are not yet available. As with other trials of torcetrapib, blood pressure was increased in the present study with torcetrapib.


Kastelein JJ, van Leuven SI, Burgess L, et al. Effect of Torcetrapib on Carotid Atherosclerosis in Familial Hypercholesterolemia. N Engl J Med 2007;356:356:1620-1630.

Presented by Dr. John J. Kastelein at the American College of Cardiology Annual Scientific Session, New Orleans, LA, March 2007.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Homozygous Familial Hypercholesterolemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Echocardiography/Ultrasound

Keywords: Carotid Intima-Media Thickness, Cholesterol, LDL, Hyperlipoproteinemia Type II, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Quinolines, Blood Pressure, Heptanoic Acids, Hypercholesterolemia, Pyrroles, Carotid Artery, Common, Cholesterol Ester Transfer Proteins, Cholesterol, HDL, Triglycerides, Disease Progression

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