Stunning Setback for Heart Drug

The announcement over the weekend that Pfizer had halted development of a potential blockbuster drug intended to treat heart disease dealt a major blow not only to the company, but to heart patients everywhere. Researchers had hoped the drug, torcetrapib, would reduce the risk of heart attack by raising the level of HDL, the "good cholesterol," in the blood. But a clinical trial involving 15,000 patients was stopped when the drug was linked to 82 deaths. That number was significantly higher than the 51 deaths among people in the trial who had not taken torcetrapib. NEWSWEEK’s Julie Scelfo spoke with Dr. Steven E. Nissen, chairman of cardiovascular medicine at the Cleveland Clinic, about torcetrapib and the aborted study. Excerpts:

NEWSWEEK: Just last week Pfizer's chief executive, Jeffrey B. Kindler, said torcetrapib could be among the most important new developments for heart disease in decades. What changed?

Steven E. Nissen: The Data Safety and Monitoring Board for major ongoing trials was looking at patient safety and saw a major increase in risk of death of those patients that got the drug.

How common is it to discover such serious problems in a late-stage trial?

That's when it usually shows up. Until you get to stage three, you haven't exposed many patients to the drug so you really can't see these hazards until you've got thousands of patients taking the drug.

Why was there so much anticipation that this drug would make it to market?

Everybody believed that raising the good cholesterol, HDL, ought to have a beneficial effect. And this drug was very powerful at raising HDL—it could raise it by at least 50 percent--and that led to very high expectations.

How does torcetrapib differ from statin drugs like Lipitor?

Statins lower the bad cholesterol, or LDL, via the liver. This drug works by a different mechanism to raise the good cholesterol, HDL.

Nissen says there were high expectations for torcetrapib

What do these deaths suggest about other drugs that are intended to raise HDL?

There are two possibilities. One is it is an effect due to toxicity of this specific drug, torcetrapib. It's also possible other drugs in the class would cause the same adverse effect, so it's put a chill on developing the entire class.

You were the principal investigator for another torcetrapib study. What did that study examine?

It was looking to see if torcetrapib-treated patients had a slower rate of progress of plaque build-up in coronary arteries. That study will be reported in March at the American College of Cardiology as originally planned.

Are there any other HDL-raising drugs currently in the works?

There are some, but they are a long way off. I don't see anything developing before 2011 at the earliest.

What about Niaspan, a drug containing the B-vitamin niacin?

It's been around a long time. It's actually generically available. The biggest problem we have, however, is that it has a lot of side effects and it's very difficult for many patients to take it. And its effect is only modest.

Does niacin alone have the potential to help raise HDL?

Niacin is very effective. But not everybody can take it. It has a lot of side effects like flushing and itching of the skin.

Are there other, non-pharmacological ways to increase good cholesterol?

You can raise HDL a little bit by modest alcohol intake and also by exercising frequently. But it's tough to move it up significantly. If we see a five or six percent increase that's about as much as we can expect.

So this news was really crushing.

It's terrible. I feel very bad about this on behalf of my patients. Despite statin drugs, a lot of people continue to have heart attacks and strokes. It's the number one cause of death among men and women.