Elevation of high-density lipoprotein cholesterol with torcetrapib does not appear to slow progression of atherosclerotic plaque in coronary arteries, according to late-breaking clinical trial data presented at the scientific session of the American College of Cardiology.

The Investigation of Lipid Level management using coronary UltraSound To assess Reduction of Atherosclerosis by CETP Inhibition and HDL Elevation (ILLUSTRATE) trial enrolled 1,188 patients with coronary artery disease who had a clinical indication for cardiac catheterization; each also underwent a baseline intravascular ultrasound examination. Then, participants 10-80 g atorvastatin adjusted during a 2- to 10-week period until low-density lipoprotein cholesterol levels reached national guidelines.

Patients were then randomized to 60 mg torcetrapib or placebo for two years. At the end of the treatment period, a second ultrasound examination was performed. Researchers measured change in plaque volume in coronary comparing baseline with follow-up ultrasound. They also measured patients' blood cholesterol levels and biomarkers of inflammation at several points during the trial.

Patients in the torcetrapib/atorvastatin group had a 61-percent relative increase in high-density lipoprotein cholesterol levels and a 20-percent relative decrease in low-density levels compared with patients in the atorvastatin/placebo group.

Despite those results, there was no statistical difference between groups in plaque volume change. Plaque volume increased by 0.19 percent in atorvastatin patients and by 0.12 percent in the combination group. Torectrapib was also associated with a substantial increase in blood pressure, averaging 4.6 mm Hg.

Steven Nissen, MD, Chairman of Cardiovascular Medicine at Cleveland Clinic and lead investigator of the clinical trial, presented the study, which was simultaneously published in the New England Journal of Medicine.

All development of the drug was terminated on December 2, 2006 after the safety board monitoring a separate large clinical outcomes trial reported that torcetrapib increased the risk of death and other adverse cardiovascular outcomes.

"We found that the torcetrapib/atorvastatin combination markedly increased good cholesterol levels and lowered bad cholesterol in patients. Unfortunately this drug also substantially raised blood pressure and failed to slow the buildup of plaque," Nissen said. "It is yet to be determined of this failure represents a problem unique to torcetrapib or predicts a lack of efficacy for the entire class of similar drugs. These findings further demonstrate the great difficulty in developing therapies to disrupt the atherosclerotic disease process."