News
ACAT inhibitor unsuccessful at limiting atherosclerosis
Trial findings released last week at the American Heart Association scientific sessions 2005 in Dallas, Texas, have cast doubt on whether a promising novel drug class can slow the progression of atherosclerosis.
The trial, known as ACTIVATE, found that the acyl-coenzymeA: cholesterol O-acyltransferase (ACAT) inhibitor pactimibe did not reduce atheroma volume, measured using intravascular ultrasound, and might even increase it in some areas.
Presenting investigator Steve Nissen (Cleveland Clinic, Ohio, USA) said that, despite the negative findings, lessons had been learned.
"I would call this a successful failure because there are at least a half a dozen drugs in this class that are under development and I would recommend to those companies that they reconsider whether they want to move forward or not," he said.
ACAT inhibitors have reduced the progression of atherosclerosis in previous studies in mice, in certain cases even reversing it.
The ACAT Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE) study aimed to examine whether the agent had similar effects in 534 men and women with symptomatic coronary artery disease from 52 US medical centers.
Participants were randomly assigned to receive 100 mg pactimibe or placebo for 18 months, in addition to conventional therapy including statins.
Intravascular ultrasound performed at the start of the study and at the end of follow-up revealed that the primary endpoint of change in percent atheroma volume increased significantly in both groups and showed a trend towards being greater with pactimibe.
In addition, secondary endpoints of change in atheroma volume of the total artery and also in the most diseased segment showed significantly greater regression with placebo than pactimibe (p=0.04 and p=0.01, respectively).
However, Nissen noted that pactimibe was not associated with an increased risk of myocardial infarction, stroke, and other cardiovascular disease endpoints.
"So while it did slightly increase the progression rate of the disease, there was no evidence of clinical harm."