WEDNESDAY, May 14, 2008 (HealthDay News) -- A new Canadian study confirms that people given Trasylol, a drug used to reduce bleeding during heart surgery, face a 53 percent increased risk of death.
Trasylol's German maker, Bayer AG, suspended marketing in the United States last November after preliminary results from this trial revealed problems with the medication. On Wednesday, following release of the new findings, the U.S. Food and Drug Administration said the manufacturer had begun removing any remaining stock of the drug from the U.S. market.
"In the trial, we asked whether aprotinin [Trasylol] was more effective at reducing massive bleeding during high-risk heart surgery compared to other drugs," lead investigator Dr. Dean A. Fergusson, from the University of Ottawa Centre for Transfusion Research, said during a teleconference Monday.
"We also asked were serious complications, such as death and organ failure, lower for aprotinin compared to the two other drugs," Fergusson said.
The report was released online Wednesday by the New England Journal of Medicine and will appear in its May 29 issue.
In the Canadian trial, known as BART, Trasylol was compared with two similar drugs Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid).
During the trial, 2,331 high-risk cardiac patients undergoing heart surgery were randomly assigned to one of the three drugs.
"The most important outcome of the trial was a bit of surprise," co-principal investigator Dr. Paul C. Hebert, a critical care physician at Ottawa Hospital, said during Monday's teleconference.
The rate of death from Trasylol was 6 percent versus 3.9 percent and 4 percent for the other two drugs, Hebert said. "This represents a 53 percent of relative risk of dying, which translates into for every 50 patients treated with aprotinin, one patient would die," he said.
Most of the deaths associated with Trasylol were from cardiac complications, Hebert said. Because of the significant increased risk of death, the trial was stopped in October 2007, before the scheduled completion date.
The researchers concluded that while Trasylol may have a small advantage in reducing massive bleeding, the increased risk of death precluded the use of the drug in patients undergoing high-risk heart surgery. "That's the statement at the end of the paper, and we stick by it," Hebert said.
However, despite the drug being pulled off the market in many countries, Bayer continues to sell Trasylol in some areas of the world.
"Trasylol, currently under temporary market suspension worldwide, continues to be available in some countries under special access programs as reviewed and agreed to with the relevant regulatory bodies in those markets," said Bayer spokeswoman Staci Gouveia.
Gouveia noted that Bayer is continuing to keep its options open as to whether it will try to reintroduce the drug.
"Bayer will continue to carefully review this article, the editorial and [when available] the underlying data on which the authors have based their conclusions and continue to discuss both the restricted access programs for Trasylol and the worldwide temporary marketing suspension of the drug with regulatory authorities," Gouveia said.
But one expert thinks the results of this trial end the use of Trasylol during cardiac surgery.
"For all practical purposes, unless there is surprising new data, the BART findings preclude future use of aprotinin in cardiac surgery, even though we don't fully understand why the increased risk of death occurs," said Wayne A. Ray, director of the Division of Pharmacoepidemiology at Vanderbilt University School of Medicine and author of an accompanying journal editorial.
Ray noted that the results of this trial were different from those of other trials, which found no increased risk of death.
"However, this was because the earlier trials were mostly small and not designed to study death," Ray said. "Future studies of drugs to prevent blood loss in cardiac surgery must be designed to look at death and other important clinical consequences, rather than only focusing on blood loss."
Another expert thinks the study starkly shows the dangers of Trasylol.
"This is yet another striking demonstration of the risk of aprotinin," said Dr. Eric J. Topol, director of the Scripps Translational Science Institute and dean of the Scripps School of Medicine.
Trasylol had been on the market since 1987 and was widely used.
The big questions remaining are "why it takes so long for the truth to come out? And how many patients were lost because of this misadventure in therapeutics?" Topol said.
Topol thinks there is enough blame to go around. "Did the clinical community accept it too readily? Was the manufacturer not willing to do the appropriate trials?" he asked.
The U.S. Food and Drug Administration is also very high on the blame list, Topol said. "The FDA has to be considered part of the problem," he said. "Why weren't trials like this part of the early approval process, rather than getting the data many years later?"
For more on heart bypass surgery, visit the U.S. National Library of Medicine.