Blood Drug Trades Benefit for Risk: New Thinner Reduces Heart Attacks but Increases Serious Bleeding

Nov 05, 02:10 AM

Current Headlines: By John Fauber, Milwaukee Journal Sentinel

Nov. 5--ORLANDO -- When the blood-thinning drug aspirin became standard therapy for heart patients in the 1970s, doctors knew they were making a tradeoff: fewer heart attacks, strokes and cardiovascular deaths, but an increase in serious bleeding.

Next came the blood-thinning drug Plavix (clopidogrel) in the late 1990s and more of the same: fewer cardiovascular deaths, but also more cases of serious and potentially fatal bleeding.

Now a new study involving 13,608 people with severe heart disease has found that the experimental blood-thinner prasugrel reduced heart attacks, strokes and cardiovascular disease deaths by 19% compared with clopidogrel in patients who had undergone procedures to open blocked coronary arteries.

And once again the risk of bleeding increased.

Like aspirin and clopidogrel before it, prasugrel works by preventing platelets in the blood from sticking together. And like the other drugs, it seriously ramps up the risk of bleeding. A total of 146 people in the study who got prasugrel (2.4%) experienced major bleeding, compared with 111 (1.8%) who got clopidogrel.

"This is pushing it further," said Matthew Wolff, a cardiologist at the University of Wisconsin Hospital and Clinics in Madison. "The question is, where does it start becoming a bad deal?"

Whether prasugrel eventually is approved by the Food and Drug Administration and whether it someday becomes standard therapy in the treatment of serious heart disease remains to be seen.

But doctors who were not associated with the trial said the drug potentially could be used in hundreds of thousands of heart patients each year in the United States. The drug it is seeking to replace, clopidogrel, is one of the most prescribed drugs in the world and now is being taken by millions of Americans.

The research was presented Sunday at the American Heart Association's annual meeting in Orlando and published online in the New England Journal of Medicine.

"The U.S. public wants everything to be 100 percent safe," said Raymond Gibbons, a cardiologist and professor of medicine at the Mayo Clinic. "Everything we do has risk."

Gibbons, who was not a part of the study, said he believed the potential benefits of prasugrel outweighed the risks.

Prasugrel is a more potent anti-platelet agent than aspirin and clopidogrel, which now are standard therapy for people who undergo angioplasty and have stents placed in their coronary arteries. As might have been predicted, it reduced heart attacks and strokes and increased serious bleeding, said Spencer King, a cardiologist at Piedmont Hospital in Atlanta and spokesman for the American College of Cardiology.

King, who was not a co-author of the prasugrel study but served on the committee that monitored the safety of the drug, said prasugrel likely will be approved and many doctors will want to use it.

"A lot of it will depend on pricing," he said.

He noted that clopidogrel, which costs about $4 a day, will become a generic drug in 2011, which means it likely will be substantially cheaper than prasugrel if prasugrel gets FDA approval.

But that is not a sure thing, and additional research may have to be done because of the increased bleeding risk, said Gordon Tomaselli, a professor of medicine at Johns Hopkins School of Medicine.

"This is going to be a very troubling finding for the FDA," said Tomaselli, who was not a part of the trial.

The study's authors said using prasugrel resulted in 23 fewer heart attacks for every 1,000 patients treated, compared with clopidogrel. But there were six additional cases of major bleeding, or a 32% increase.

Still, even with the additional bleeding the sum of all negative events was lower in the prasugrel group (14% vs. 12%) over the 15 months of the study.

"I think this is definitely an approvable drug," said senior author Elliott Antman, a professor of medicine at Harvard Medical School.

The study was funded by Daiichi Sankyo and Eli Lilly, the makers of the drug. Antman and most of the study's co-authors have financial arrangements with those companies as well as Sanofi-aventis and Bristol-Myers Squibb, which sell clopidogrel.

Antman noted that much of the bleeding risk occurred in a small group of patients: those who had a prior stroke or who were older than 75 or who weighed less than 132 pounds.

He said it makes sense that the drug would cause more problems for an "elderly grandmother than a large, muscular body builder."

Not giving it to the high-risk patients could eliminate a lot of the bleeding risk, he said.

UW's Wolff said one potential problem with the trial was the way the drugs were administered. For most of those in the trial, the two drugs were given during the angioplasty procedure rather than before, which is the recommended method.

That's because in about 10% of angioplasties doctors learn during the procedure that the patient actually needs a much more invasive operation known as coronary artery bypass surgery.

Because of the high bleeding risk, those patients must then remain in the hospital for up to a week until the bleeding risk is reduced before the surgery can be done.

That adds a great deal of time and expense, Wolff said.

While the study might have compared the two drugs when they were given before the procedure started, the reality is that most doctors don't give clopidogrel until after the procedure starts, the same way they likely would use prasugrel, he said.

He added, "This study is very promising."

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