The ILLUSTRATE trial finds no significant slowing of coronary atheroma progression from torcetrapib despite reaching an LDL-to-HDL ratio below 1.0 (N Engl J Med 2007)

Original title: Effect of torcetrapib on the progression of coronary atherosclerosis

N Engl J Med · 26 March 2007 · 8

Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, Ruzyllo W, Bachinsky WB, Lasala GP, Tuzcu EM, ILLUSTRATE Investigators

This intravascular ultrasound trial in 1,188 patients with coronary disease tested whether torcetrapib could slow coronary atherosclerosis progression. After atorvastatin lowered LDL cholesterol below 100 mg per dL, patients were randomized to atorvastatin monotherapy or atorvastatin plus torcetrapib 60 mg daily, with disease progression assessed by repeat intravascular ultrasound in 910 of the 1,188 patients (77%) after 24 months. Torcetrapib-atorvastatin produced an approximate 61% relative increase in HDL cholesterol and a 20% relative decrease in LDL cholesterol, reaching an LDL-to-HDL ratio below 1.0, but was also associated with a 4.6 mmHg rise in systolic blood pressure. The primary efficacy measure, percent atheroma volume, increased 0.19% with atorvastatin alone versus 0.12% with torcetrapib-atorvastatin (p = 0.72), a non-significant difference, though a secondary measure of normalized atheroma volume showed a small favorable effect for torcetrapib (p = 0.02) with no significant difference in the most diseased vessel segment. The findings show no significant slowing of coronary atherosclerosis progression from torcetrapib despite its substantial lipid benefits.

Original abstract

Background: Levels of high-density lipoprotein (HDL) cholesterol are inversely related to cardiovascular risk. Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor, increases HDL cholesterol levels, but the functional effects associated with this mechanism remain uncertain.

Methods: A total of 1188 patients with coronary disease underwent intravascular ultrasonography. After treatment with atorvastatin to reduce levels of low-density lipoprotein (LDL) cholesterol to less than 100 mg per deciliter (2.59 mmol per liter), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated intravascular ultrasonography in 910 patients (77%).

Results: After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib-atorvastatin therapy was an approximate 61% relative increase in HDL cholesterol and a 20% relative decrease in LDL cholesterol, reaching a ratio of LDL cholesterol to HDL cholesterol of less than 1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib-atorvastatin group (P=0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (P=0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment.

Conclusions: The CETP inhibitor torcetrapib was associated with a substantial increase in HDL cholesterol and decrease in LDL cholesterol. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects. (ClinicalTrials.gov number, NCT00134173 [ClinicalTrials.gov].).

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