Blood-Loss Drug a Risk to Patients, Research Finds

By Marc Kaufman

A popular drug given to more than a million people since 1993 to limit blood loss during heart surgery doubles a patient’s risk of kidney failure and substantially increases the risk of a heart attack, a major study has found.

The research, being published today in the New England Journal of Medicine with a supportive editorial and commentary, concluded that use of the drug — Bayer Corp.’s aprotinin — causes more than 11,000 patients worldwide to need kidney dialysis each year.

The authors said that in light of their findings, and the fact that two other less harmful and far less expensive alternatives exist, it is no longer “prudent” for doctors to use the drug except in unusual circumstances. If they continue with the drug, the authors said, doctors have a moral obligation to inform patients about the risks.

The Food and Drug Administration said it is reviewing the study and “will make recommendations for best use as soon as possible.” Bayer said it had only recently become aware of the research and it is “not consistent with the more than 15 years of clinical data and experience Bayer has amassed on this drug.”

With the industry and the agency still reeling from the contentious withdrawal of the arthritis drug Vioxx in 2004 because of safety concerns, the new finding underscores how difficult it is to know the risks of a drug once it goes on the market.

“We have a real problem with safety once a drug is approved,” said study lead author Dennis Mangano of the Ischemia Research and Education Foundation in California, a nonprofit group that has been collecting and analyzing the aprotinin data since 1996.

Aprotinin, sold as Trasylol, has been widely studied since it was approved in 1993, but most of the research has focused on its effectiveness.

Mangano’s research, however, found not only a greatly increased rate of kidney failure, but also a 50 percent increase in heart attacks and an almost 200 percent increase in strokes. The study also found that two other generic drugs in a different class were as effective as aprotinin in staunching bleeding after surgery, were safer and cost less than one-tenth the price. In its statement, the FDA said it would now compare the safety of aprotinin and the other products.

The study was based on data collected from 4,374 patients at 69 sites worldwide who underwent heart or coronary artery surgery. About 1,300 were given aprotinin, about 1,300 received no drug to stop bleeding, and more than 800 were treated with each of the two other generic anti-bleeding agents. Although the study was not a placebo-controlled and randomized clinical trial — considered the gold standard for medical research — it followed enough patients to give it “credibility,” wrote Gus Vlahakes, chief of cardiac surgery at Massachusetts General Hospital, in an accompanying editorial.

Mangano said the increased risk of kidney failure makes sense physiologically because it is known that aprotinin, which is derived from the lung tissue of cows, generally stays in the kidneys for 24 hours and can cause damage.

The two other drugs used to limit bleeding in the study are generally excreted quickly by the body.