Fatal flaw? Antibleeding drug faces new safety questions.

A drug commonly used to slow bleeding during heart surgery increases a patient's risk of dying during the next 5 years, a new study suggests.

U.S. heart surgeons have used the drug, called aprotinin, for 14 years. But last year, researchers reported that people receiving it had heightened risks of kidney problems, heart attack, and stroke. Those findings prompted the U.S. Food and Drug Administration to change the labeling on aprotinin to limit its use to coronary-bypass surgery patients at high risk of blood loss.

In the new study, researchers analyzed the risk of death from any cause for 3,876 heart-bypass surgery patients during the first 5 years after their operations. Some patients had received aprotinin during surgery, while others got one of two other drugs that are sometimes used during coronary-bypass surgery but have been approved to suppress bleeding only under other circumstances. Patients who had received no antibleeding agent served as a comparison group.

The people who had received aprotinin were about 60 percent more likely to die within 5 years than were the patients who had gotten no drug. In contrast, mortality among people who received one of the other drugs was no higher than that in the comparison group, the scientists report in the Feb. 7 Journal of the American Medical Association (JAMA).

The alternative drugs--aminocaproic acid (Amiear) and tranexamic acid (Cyklokapron)--are less expensive than aprotinin and just as effective at decreasing bleeding during bypass surgery, says study coauthor Dennis T. Mangano of the Ischemia Research and Education Foundation in San Bruno, Calif.

However, many surgeons prefer aprotinin to the alternative drugs to reduce bleeding during heart surgery, says epidemiologist Jeremiah R. Brown of Dartmouth-Hitchcock Medical Center in Lebanon, N.H. "They say it gives them a cleaner [surgical] field" in which to operate, he says.

Aprotinin is marketed as Trasylol by Bayer Pharmaceuticals in Levekusen, Germany.

Cardiologist Robert A. Harrington of the Duke University School of Medicine in Durham, N.C., says that the new study suffers because doctors chose which of the treatments to deliver--rather than randomly assigning them to patients.

Indeed, in these operations, patients who received aprotinin or the alternative drugs were more likely to have undergone complex surgery than were the patients who received no antibleeding drug, notes physician T. Bruce Ferguson Jr. of East Carolina University School of Medicine in Greenville, N.C., writing in the same issue of JAMA. Despite adjustments for patient differences, the potential for biases makes this study controversial, he says.

Meanwhile, heart surgeons wrestle with a trade-off, Harrington says. Does reducing the need for a blood transfusion with the FDA-approved use of aprotinin outweigh the adverse effects that the drug might have later? A randomized trial might settle the issue, Harrington says.