TORONTO - A new analysis of clinical trials of a controversial anti-bleeding drug used in heart surgery says that cheaper, safer alternatives work nearly as well and should be recommended.
The review was rushed to print Tuesday by the Canadian Medical Association Journal in advance of a hearing Wednesday of a panel of experts who have been asked to advise Health Canada on future use of the drug, aprotinin.
"For routine use there is no clear advantage of aprotinin that justifies the apparent increase in mortality and the undoubted increase in cost," said Dr. David Henry, lead author of the review and CEO of the Institute of Clinical Evaluative Sciences in Toronto.
"So that in routine clinical practice, there is not now a role for this drug as an adjunct to cardiac surgery."
Aprotinin - which is sold under the brand name Trasylol - was used to reduce bleeding and minimize the need for blood transfusions during coronary artery bypass surgery. Made by pharmaceutical giant Bayer Inc., the drug was thought to be more effective than older anti-bleeding therapies tranexamic acid and aminocaproic acid.
But a landmark clinical trial comparing aprotinin to the alternatives was stopped in October 2007 when it was found that the rate of deaths among people who were given the drug was higher than that of people who got the older, cheaper drugs.
Called the BART trial and led by researchers at the Ottawa Health Research Institute, that study found the rate of deaths among people who got aprotinin was 50 per cent higher than that of the people who got two older anti-bleeding drugs.
Put another way, they found that for every 100 patients who got aprotinin during high-risk cardiac surgery, six died. For every 100 patients getting tranexamic acid or aminocaproic acid, four died. The findings were published in May in the New England Journal of Medicine.
The drug is currently the subject of a number of class action lawsuits in the United States and Canada.
Based on the BART trial findings, Health Canada asked Bayer last November to suspend marketing the drug in this country. The drug maker complied and announced it was temporarily suspending marketing of the drug worldwide. But it said it would make the drug available through a special access program for the very high risk surgeries in which it is still thought to be the preferred treatment.
Henry and his group have been studying the results of clinical trials of these types of drugs - known as antifibrinolytics - for the past decade for the Cochrane Collaboration, an international not-for-profit organization that aims to improve health care by regularly gathering up the best scientific data about a drug, medical procedure or health intervention and publishing the resulting analysis.
A 2007 Cochrane review on anti-bleeding drugs by Henry and his colleagues found the medications in the class did not increase rates of death or heart attacks in people who were given them during surgery.
With the publication of the BART trial results, the group conducted a new analysis, looking at data from new clinical trials in addition to the previously analyzed studies.
The picture that came into focus, Henry said, is that aprotinin is probably a bit better at controlling bleeding than the other drugs, "but the effects seem to be quite small."
For some patients at severe risk of hemorrhaging during bypass surgery, aprotinin might be the better option, he admitted - but the available data can't help doctors figure out who they are.
"We legislate and regulate for the average individual," Henry said.
"Therefore the regulatory decision will be based on the average individuals, not the exceptional case. And I have to say to be honest that our data don't allow us to . . . clearly identify the subgroup in whom the benefits outweigh the harms. So consequently there is a case to be made for not using the drug."
