WEDNESDAY, Jan. 25, 2006 (HealthDay News) -- A widely promoted drug used to prevent bleeding during heart surgery doubles the risk of kidney failure and increases the risk of heart attack, heart failure and stroke, a study finds.
Two less expensive generic drugs used for the same purpose do not carry the same dangers, said a report in the Jan. 26 issue of the New England Journal of Medicine.
The study looked at data on 4,374 patients who had surgery after heart attacks and is "the largest study yet done," said Dr. Dennis T. Mangano, director of the Ischemia Research and Education Foundation, a California-based nonprofit organization, and lead author of the report.
It compared the outcomes of operations in which patients undergoing coronary artery surgery were given either one of three drugs to reduce bleeding: aprotinin, the newer agent; aminocaproic acid; tranexamic acid; or no drug at all.
The incidence of kidney failure in patients who got aprotinin was more than double that of those who got either of the two other drugs or no drugs at all, the report said. The risk of stroke was 181 percent higher, while the incidence of heart attack or heart failure was 55 percent higher.
The study was done because previous, smaller trials indicated an increased risk associated with aprotinin, but none of them was large enough to be definitive, Mangano said.
Aprotinin was approved by the U.S. Food and Drug Administration in 1993. It is marketed by Bayer HealthCare under the brand name Trasylol.
A statement from Bayer said it "has only just become aware of this observational study" and has not yet reviewed its findings. But the company said the reported increases in risks "are not consistent with the more than 15 years of clinical data and experience Bayer has amassed on this drug." Bayer said its claim of safety was based on controlled trials including almost 6,500 heart-surgery patients.
Mangano countered by saying those studies looked at the effectiveness of the drug, not at its safety. "There is no financial incentive for the drug industry to do safety trials after approval," he said.
And a study looking at safety "would find it very difficult to enroll patients," Mangano said. "You would be telling patients they would get a protein that promotes kidney failure."
The fact that aprotinin is a protein, while the other drugs are different chemically, could account for the reported kidney damage, he said. A protein is taken up by the kidney, where it remains for 24 hours and can change kidney function, Mangano said. He estimated that 10,000 Americans now require artificial kidneys because they were given aprotinin.
The Bayer statement said the new study was not the kind of randomized, controlled trial that is "the accepted standard for the safety and efficacy of drugs."
In an accompanying editorial in the journal, Dr. Gus J. Vlahakes of Massachusetts General Hospital said that "regulatory requirements and the desire to ensure approval often dominate the design of clinical trials."
The desire to get a drug approved quickly often leads to selection in trials of patients who are least likely to have adverse reactions, said Vlahakes, who is chief of cardiac surgery at the hospital. But once a drug is approved, the company is free to push for expanded uses, he said.
The new study shows the need for continued testing of drugs after their first approval, Vlahakes said. "This process of phase 4 testing [after approval] I think is very important and something the FDA might want to require," he said.
In the case of aprotinin, Bayer has proposed its use for all heart-surgery patients, saying the drug can prevent an inflammatory reaction often caused by use of a heart-lung machine during the operation, Vlahakes said. The results of the study "are a strong suggestion that you can't just put aprotinin in the repertoire for all patients," he said.
At Massachusetts General Hospital, heart-surgery patients are generally given one of the older drugs, with aprotinin used "only in select circumstances where we expect to have particular difficulty with bleeding," Vlahakes said. Experience has shown that half the recommended dose is fully effective, he said.
You can learn about heart attack from the National Library of Medicine.