WASHINGTON, Jan. 25 (UPI) -- A major independent study indicates Bayer's antifibrinolytic agent Trasylol doubles the risk of kidney failure and causes other serious adverse events, including stroke and heart attack.
The finding is likely to significantly impact sales of the drug, which were expected to be more than $600 million this year.
"The study raises serious questions about the continued use of Trasylol and suggests far less expensive alternatives are available that are equally effective and safe," the study's lead author, Dennis Mangano of the Ischemia Research and Education Foundation in San Bruno, Calif., told United Press International.
Trasylol, which has been on the market for 13 years, reduces the loss of blood during surgery and is typically used during certain heart operations.
Two generic drugs -- aminocaproic acid and tranexamic acid -- were just as effective and safer, the research team concluded in the Jan. 26 issue of The New England Journal of Medicine.
Mangano and colleagues stated in the article that using one of the generic drugs instead of Trasylol worldwide could prevent as many as 11,050 dialysis complications, save $1 billion in healthcare costs and reduce drug costs by $250 million.
The team also estimates that as many as 10,000 patients may now be on dialysis due to Trasylol. "I'm concerned about that, but I'm even more concerned about -- now that we know there is a problem -- how many new patients that receive the drug will develop renal failure," Mangano said.
He noted the life-threatening side effects associated with Trasylol occurred more frequently than those associated with Merck's Vioxx, which was taken off the market in 2004 after it was linked to an increased risk of heart attacks and strokes.
Asked whether he thought Trasylol should be withdrawn from the market, Mangano said that was a regulatory matter that he could not address. But he added, "In good conscience, I could not administer (Trasylol) to this group of patients, especially given the availability of safer alternatives."
If a physician still wants to use the medication, Mangano said, "The least that should be done is to inform the patient that the risk of going on dialysis is increased 2-3 fold and there are alternatives."
In the study, data was collected from more than 4,300 patients undergoing revascularization surgery at more than 69 centers around the world between 1996 and 2000. The patients received either Trasylol, aminocaproic acid, tranexamic acid or no treatment.
The Trasylol group had double the risk of renal failure requiring dialysis usually observed in patients undergoing complex coronary-artery surgery or primary surgery. The group also had a 48-percent increased risk of heart attack, a 109-percent increased risk of heart failure and a 181-percent increased risk of stroke or encephalopathy.
Neither group that received the generic drugs exhibited these increased risks.
Bayer was quick to defend its drug and shed doubt on the new study. The company said it "believes that Trasylol is a safe and effective treatment" and that the "increases in renal failure, myocardial infarction, congestive heart failure and stroke or encephalopathy associated with use of (Trasylol) in patients undergoing coronary-artery surgery are not consistent with the more than 15 years of clinical data and experience Bayer has amassed on this drug."
Bayer noted that clinical trials it has conducted with Trasylol have included more than 3,800 patients who received the drug whereas this current study only consisted of 1,295 patients. The company also faulted the study design, saying it was an observational trial and not a double-blind, randomized controlled trial.
Mangano, however, pointed out that Bayer's trials were small and no one study included as many patients as his current report. Regarding the study design, he said it is nearly impossible to do a randomized, double-blind study once a drug is on the market.
Mangano's colleagues seem to agree with him. Writing in an accompanying perspective, David Hunter, an epidemiologist at the Harvard School of Public Health, said it is an example of the type of study that may be a model for the future.
"Studies such as the one by Mangano and colleagues point the way to the prospective design of studies to assess drug safety and to the collection of as much information as necessary to provide answers of the highest quality," Hunter wrote.
"Substantial questions remain about how to fund and administer these studies, but we need to ensure that skepticism about the value of observational studies does not engender nihilism," he added. "In the absence of evidence from randomized trials, the best-quality data must be made available to ensure the safety of medications."
Gus Vlahakes, of Harvard Medical School and Massachusetts General Hospital, concurred, saying the study illustrates the importance of conducting phase 4 studies.
Noting that efforts are under way to expand Trasylol's indications, which could require higher doses of the drug, Vlahakes wrote in an accompanying editorial, "Phase 4 clinical trials should be required before the indications for pharmaceutical agents are expanded, particularly when increased doses are required or administration in high-risk patients is proposed."
He also encouraged the FDA to support the use of independent clinical research in phase 4 testing. Referring to the recent problems with Vioxx and other COX-2 inhibitors, he said, "Too many pharmacologic agents have entered into clinical practice for which considerable and potentially life-threatening outcomes were recognized only after a large number of patients had been treated."
