Trial Cholesterol Drug Strikes Out
Torcetrapib Fails to Slow Plaque Buildup in Arteries
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 plus placebo.
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.
Similarly, in the RADIANCE 1 and 2 studies, people who suffered from inherited cholesterol disorders were randomly assigned to treatment with the Lipitor-torcetrapib combination or Lipitor alone.
Torcetrapib again led to robust increases in HDL cholesterol and dramatic decreases in LDL cholesterol. However, there was again no benefit in plaque buildup. Again, blood pressure increased, although less than in the ILLUSTRATE trial.
“You would think the LDL decrease is more important than the blood pressure increase, so even ignoring HDL, we should have seen benefit,” says researcher John Kastelein, MD, of the Academic Medical Center in Amsterdam. “Something very strange is going on here,” he tells WebMD.
They researchers say they will continue to analyze the data.
There are still many unanswered questions, says James Stein, MD, of the University of Wisconsin Medical School in Madison and chairman of the session at which the results were presented.
"The big question that every scientist and everybody on Wall Street wants to know is whether or not it was the drug or the approach to raising HDL cholesterol. Most people seem to think it's unique to torcetrapib alone, but we still don’t know,” he says.
Nissen says there are three possible reasons why the drug failed. First, increases in blood pressure may have countered any beneficial effects. Second, the rise in blood pressure may reflect some other unique toxicity that doomed the drug to fail. Or third, the strategy itself may be flawed.
HDL Shots Offer Hope
Also at the meeting, researchers reported that infusions of a reconstituted form of HDL slightly slowed plaque buildup in arteries.
“They took blood, extracted HDL, turned it into a product, and reinfused it. The results offer a glimmer of hope,” Nissen says.