Trial Cholesterol Drug Strikes Out
Torcetrapib Fails to Slow Plaque Buildup in Arteries
March 27, 2007 (New Orleans) -- Three new studies show that the novel
cholesterol drug torcetrapib fails to slow plaque buildup in the arteries.
Torcetrapib was also recently linked to an increased risk of heart attacks
and death. Additionally, the new drug may raise blood pressure, the research
Despite the setbacks, experts say there may still be a role for drugs
similar to torcetrapib aimed at preventing heart disease by raising
"good" HDL cholesterol.
In December, Pfizer Inc. announced it was stopping clinical trials of
torcetrapib because of the increased heart risks associated with its use.
But researchers are continuing to analyze previously accumulated data in
hopes of finding out why the drug failed.
Approach Still Promising
“A lot of people think it's the next big thing, so we need to understand
what went wrong with torcetrapib to move forward,” says Steven Nissen, MD, head
of cardiovascular medicine at The Cleveland Clinic and president of the
American College of Cardiology (ACC).
“We believe the failure doesn't necessarily rule out the possibility that
another drug in the class, one that is completely clean, with no blood pressure
effects and no other evidence of toxicity, could possibly work," he tells
Nissen notes that if Baycol had been the first statin tested and research
had stopped after safety problems emerged, statins would never have been
developed. Baycol, sold by Bayer AG, was withdrawn from the market in 2001
after reports of a severe and sometimes fatal muscle disorder.
“We don’t want to abandon a potentially lifesaving drug, but the bar has
been raised. We have to move forward carefully,” he says.
A Strategy of Boosting HDL
Doctors say there is an urgent need for drugs that fight heart disease in
novel ways. While credited with making a substantial dent in heart disease,
statin drugs that lower "bad" LDL cholesterol don’t help everyone: Some
statin users suffer heart attacks anyway.
“You could put statins in the blood supply, and cardiovascular disease would
still be the leading cause of death. We need something else,” Nissen says.
That’s why doctors have been trying to boost levels of HDL cholesterol,
which ferries cholesterol from the bloodstream to the liver where it can be
Torcetrapib works by inhibiting an enzyme responsible for transforming good
cholesterol into bad cholesterol. “If you block this enzyme, HDL goes up and
LDL goes down,” Nissen says.
Torcetrapib Linked to BP Rise
In the new studies, torcetrapib boosted HDL cholesterol just like it was
supposed to. However, there were negative effects as well.
In one study, known as ILLUSTRATE, 1,188 patients with heart disease were
randomly assigned to receive the statin Lipitor plus torcetrapib or Lipitor
Results showed that torcetrapib boosted levels of HDL by 61% and decreased
LDL by 20%. However, people on the drug experienced a 4.6-point increase in
blood pressure. As shown by imaging, there was no significant difference in
plaque buildup between the two groups.