The development of this drug was originally terminated by Pfizer after a separate clinical trial reported that it increased the risk of death and other adverse cardiovascular outcomes.
In the trial patients were then randomized to receive either 60mg of torcetrapib plus Lipitor (atorvastatin), or a placebo plus Lipitor for two years. Patients in the torcetrapib/Lipitor group experienced a 61% increase in HDL or good cholesterol levels and a 20% decrease in LDL or bad levels, as compared with patients in the Lipitor-only group.
Despite those results, there was no statistical difference between the two groups in plaque volume changes. In the study, plaque volume increased by 0.19% in the Lipitor-only patients and by 0.12% in the combination group. Torectrapib was also associated with a substantial increase in blood pressure, averaging 4.6 mm.
“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 build up of plaque,” said Dr Steven Nissen, a Cleveland Clinic heart specialist.
“It is yet to be determined if 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.”
The development of drugs to raise HDL cholesterol has been a key research priority because, despite lowering LDL cholesterol with statin drugs, many patients continue to experience heart attacks, stroke or sudden cardiac death.