An expensive drug given to coronary artery bypass surgery patients to prevent excessive bleeding is linked to an increased risk of dying as long as five years after the operation, researchers report Wednesday.
More than 4 million patients worldwide have received aprotinin, sold as Trasylol, since 1985, the scientists write in the Journal of the American Medical Association. The Food and Drug Administration approved Trasylol for use in coronary bypass surgery patients in 1993. Last year, it was used 246,000 times in the U.S., the researchers say.
Trasylol has been under scrutiny for at least a year and has raised anew concerns about monitoring the safety of drugs once they’re on the market. The new study is a followup to one the authors published in January 2006 that linked Trasylol to serious kidney problems, heart attacks and strokes in patients undergoing coronary bypass surgery. Another study, posted online in January 2006 and published in March, also linked Trasylol to kidney trouble.
The studies spurred the FDA to convene an advisory panel
The studies spurred the FDA to convene an advisory panel, which in September voted unanimously that Trasylol should stay on the market. The next week, the FDA announced it had just learned of another study, by Trasylol maker Bayer, which the company had not mentioned at the advisory panel meeting. That study suggests that Trasylol might increase the risk of serious kidney damage, death, heart failure and strokes, the FDA said in December, when it announced updated labeling for the drug. The label now warns about kidney problems and says that Trasylol should be used only in coronary bypass surgery patients who are at an increased risk for excessive bleeding.
The new, multi-center international study compared the death rates of four groups of patients who had undergone bypass surgery: 1,072 given Trasylol, 834 given aminocaproic acid; 442 given tranexamic acid and 1,374 who didn’t receive any medication to prevent excessive bleeding. Patients who got aprotinin were about 50% more likely to die in the five years after surgery than patients who received no drug. Neither of the other drugs was linked to a significantly higher risk of death than no treatment.
Trasylol costs $1,300 per use, compared with $44 for aminocaproic acid and $11 for tranexamic acid, says lead author Dennis Mangano, head of the Ischemia Research and Education Foundation in San Bruno, Calif. Before his first study came out in January 2006, says Mangano, about half of U.S. coronary bypass surgery patients received Trasylol. But, he says, use of the drug dropped 37.5% in the first half of 2006.
I think that clinicians are going to pay attention
“I think that clinicians are going to pay attention, and I think the use of the drug will drop again,” he says.
In a statement responding to the new study, Bayer said that doctors tend to give Trasylol to the sickest of patients, which could skew findings about the drug’s safety. Based on its initial review, “Bayer believes that the results of this study should not serve as a basis for affecting the use of aprotinin.”
Keyvan Karkouti, lead author of the other paper last year linking Trasylol to kidney problems, called Mangano’s new report “a good paper, and it definitely raises more questions and concerns.”
In Canada, says Karkouti, an anesthesiologist at the University of Toronto, only bypass patients at the highest risk of bleeding 5% of bypass patients at his hospital receive Trasylol. Trasylol has been shown to be more effective than no treatment in that group, Karkouti says, but trials comparing its generic competitors with a placebo in high-risk patients haven’t been done, because no drug company stands to gain from such a study. He says a Canadian study that’s randomizing 3,000 moderate- to high-risk patients to Trasylol or one of its two generic competitors is expected to provide more answers about the drugs’ relative safety and effectiveness.