Rating Atherosclerotic Disease Change by Imaging With a New CETP Inhibitor - 2 - RADIANCE 2 – 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 mixed hyperlipidemia.

Study Design

Study Design:

Patients Screened: 2,918
Patients Enrolled: 752
Mean Follow Up: Mean 22 months
Mean Patient Age: Mean age, 57 years
Female: 36

Patient Populations:

Triglycerides >1.7 mmol/L and a concurrent LDL cholesterol that was high enough to qualify for statin treatment according to the US National Cholesterol Education Program (NCEP) Adult Treatment Panel guidelines

Primary Endpoints:

Annualized rate of change in maximum IMT for 12 carotid segments

Secondary Endpoints:

Annualized rate of change in maximum CIMT for each site; mean CIMT common carotid

Drug/Procedures Used:

Following a run-in phase in which all patients were treated with atorvastatin titrated to an achieved low-density lipoprotein (LDL) level of 2.59, 3.37, or 4.14 mmol/L, dependent on their calculated cardiac risk, patients were randomized in a double-blind manner to treatment with torcetrapib (60 mg; n = 377) in addition to atorvastatin compared with atorvastatin alone with matching placebo (n = 375). Carotid ultrasound was performed at randomization and every 6 months for 24 months.

Principal Findings:

Baseline lipid means were high-density lipoprotein (HDL) of 1.23 mmol/L, LDL of 2.60 mmol/L, total cholesterol of 4.77 mmol/L, and triglycerides of 1.88 mmol/L. Average dose of atorvastatin used in the study was 13.3 mg in the torcetrapib plus atorvastatin group and 13.2 mg in the atorvastatin monotherapy group.

At study end, HDL cholesterol was significantly increased from baseline in the torcetrapib group to 2.00 mmol/L, but stayed at 1.21 mmol/L in the atorvastatin monotherapy group (p < 0.001 for between-group comparison). Likewise, LDL reductions were greater with torcetrapib than atorvastatin monotherapy (final LDL 2.17 mmol/L vs. 2.66 mmol/L, 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 (0.025 mm/y for the torcetrapib group vs. 0.030 mm/y for atorvastatin monotherapy, p = 0.46). The rate of change differed in several subgroups. Change in maximum CIMT for each of the four common carotid-artery sites also did not differ between the torcetrapib group and the atorvastatin monotherapy group (0.022 mm/y vs. 0.020 mm/y, p = 0.65), nor did change in mean CIMT for the common carotid artery (0.013 mm/y vs. 0.008 mm/y, p = 0.06).

Serious vascular adverse events occurred in 17 patients in the torcetrapib group and 13 patients in the atorvastatin alone group. Final systolic blood pressure was 5.4 mm Hg higher in the torcetrapib group than the atorvastatin monotherapy group (127.9 mm Hg vs. 121.2 mm Hg, p < 0.001).


Among patients with mixed hyperlipidemia, 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.

In a large outcomes trial, mortality was increased with torcetrapib, prompting the trial to be discontinued and the development of the drug to be discontinued; however, the reason for the increased mortality is unknown at this time since the full findings of the trial have not yet been reported. As with other imaging trials of torcetrapib in different populations, torcetrapib was not associated with regression of atherosclerotic disease despite a marked increase in HDL cholesterol and reduction in LDL cholesterol during the study. Blood pressure increased significantly with torcetrapib in the present study, as has been observed in other trials of torcetrapib.


Bots ML, Visseren FL, Evans GW, et al. Torcetrapib and carotid intima-media thickness in mixed dyslipidaemia (RADIANCE 2 study): a randomised, double-blind trial. Lancet 2007;370:153-60.

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, Statins, Echocardiography/Ultrasound

Keywords: Cholesterol, LDL, Carotid Intima-Media Thickness, 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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