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Concerns raised on bleeding drug

CHICAGO -- A drug widely used to prevent excessive bleeding during heart surgery appears to raise the risk of dying in the five years afterward by nearly 50 percent, an international study found.

The researchers said replacing the drug -- aprotinin, sold by Bayer AG under the brand name Trasylol -- with other, less expensive medications for a year would prevent 10,000 deaths worldwide over the next five years.

The findings were more bad news for Trasylol: The same scientists found the drug raised the risk of kidney failure, heart attacks, and strokes in a study published last year. Most of the deaths in the new study were related to those problems.

Bayer said in a statement that the findings are unreliable because Trasylol tends to be used in more complex operations and the researchers' statistical analysis did not fully account for the complexity of the surgery cases.

Nevertheless, the drug company said it will "work with regulatory agencies and external experts in the field to further evaluate the findings."

The study, published in today's Journal of the American Medical Association, intensifies questions about how best to track the safety of drugs after they have gone on the market. The Food and Drug Administration approved aprotinin in 1993.

Last year's study and other research led the FDA to review Trasylol's safety and order stronger warning labels in December. But that action wasn't strong enough, said Dr. Dennis Mangano of the nonprofit Ischemia Research and Education Foundation, lead author of both studies.

The FDA is already reviewing aprotinin's safety. The new study is an important contribution to that review, which could result in additional warnings, said Dr. Dwaine Rieves, deputy director in the FDA's Division of Medical Imaging and Hematology Products.

The drug works by blocking enzymes that dissolve blood clots, and Mangano speculated that clotting problems caused the deaths.

Mangano advised patients to ask their doctors what drug, if any, they will be given to slow bleeding during heart surgery and about the risks. Past patients should find out whether they have been given aprotinin so that their doctors can watch for problems, he said.

"I believe that for the vast majority of coronary bypass patients the drug should not be used," Mangano said. But he said the drug should remain on the market because some very high-risk patients may benefit from it.

Dr. Brett Sheridan, a heart surgeon with the University of North Carolina Health Care System who was not involved in the study, said that several years ago he quit giving aprotinin almost entirely because he had seen more kidney damage in patients who got the drug.

"It's not a perfect study, but the data are compelling enough that we have to use aprotinin judiciously," Sheridan said of the new research.

The study followed 3,876 patients who had heart bypass surgery at 62 medical centers in 16 nations. Researchers compared patients who received aprotinin to patients who got other drugs or no antibleeding drugs. Over five years, 20.8 percent of the aprotinin patients died, versus 12.7 percent of the patients who received no antibleeding drug.

Researchers found that patients who got Trasylol ran a 48 percent higher risk of dying in the five years afterward.

The other drugs, both cheaper generics, did not raise the risk of death significantly.

Cost varies depending on dosage and length of surgery, but a two-hour bypass surgery might require $792 in Trasylol, compared with $7 to $35 for a generic.

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