May 15, 2008 04:30 AM
A massive Canadian study that caused a popular heart surgery drug to be pulled from the shelves last November has shown it increased the risk of death by 50 per cent over two rival medications.
Pharmaceutical giant Bayer AG voluntarily removed the anti-bleeding drug aprotinin, the generic name for Trasylol, from circulation when early results from the University of Ottawa-led study began to reveal its relative risks.
“The … study will change the way heart surgery is done around the world,” said Dr. David Mazer, an anesthesiologist at Toronto’s St. Michael’s Hospital and a co-author of the paper, the final draft of which was published online yesterday by the New England Journal of Medicine.
“As a result of the … research, patients and their doctors can have that much more confidence going forward,” Mazer told a media briefing in Ottawa this week.
“It was a bit of a surprise in seeing this,” said Dr. Paul Hebert, a critical care physician at the Ottawa Hospital and a principal study investigator.
“We’ve … shown, we think reasonably definitively, that (aprotinin) increases the risk of death as compared to two alternatives.”
Hebert said the study showed that of “every 50 patients treated with aprotinin, one (more) patient would die” over those who received either of the other clotting drugs.
Bayer has never said whether it plans to try to resuscitate aprotinin. And even with the release of the trial data, it is hedging its bets.
“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,” Bayer said in a prepared statement.
“When further conclusions are reached, Bayer will communicate publicly.”
But an editorial in the journal predicted the drug is done.
“In all likelihood, this is the end of the aprotinin story,” wrote Wayne Ray and Dr. Michael Stein, of the Vanderbilt University Center for Education and Research on Therapeutics in Nashville, Tenn.
The trial – known as BART for Blood Conservation using Antifibrinolytics in a Randomized Trial – took place in 19 centres across Canada, including St. Michael’s.
It involved more than 2,400 patients.
The trial was halted last October, about two-thirds of the way through, after it began to show clearly that six per cent of patients who received aprotinin died within 30 days of surgery. This compared to just four per cent of patients who received either of the two alternate medications, tranexamic acid or aminocaproic acid.
“Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative trends in mortality associated with aprotinin use preclude its use in patients undergoing high-risk cardiac surgery,” Hebert said, quoting from the paper.
“The risks of aprotinin are greater than its benefits,” he continued.
Between one million and 1.25 million heart surgeries are performed worldwide each year, with about 25 per cent of these being “high risk.” These include multiple bypass operations and valve work and generally require a bleeding-control drug to reduce the need for transfusions.
All three drugs help to stem such bleeding by inducing scablike clots along surgical incisions.
Researchers theorize aprotinin’s superior ability to control bleeding – it was found to be about 20 per cent more effective than the others – may account for the greater risks it poses.
Earlier small-scale studies appeared to indicate that aprotinin was more dangerous than the other two medications, leading the U.S. Food and Drug Administration to issue a 2006 warning on its use.
Millions of patients would have been given the drug over the last decade, researchers say.
The BART study was sponsored by The Canadian Institutes of Health Research and the Ontario health ministry.