Results from an eagerly-awaited Canadian study appear to have put paid to any hopes that Bayer may have had of getting its controversial heart surgery drug Trasylol back onto the market.

Bayer voluntarily suspended sales in November 2007 after the aforementioned Canadian study from the Ottawa Health Research Institute, called BART, was stopped because of patient deaths. The company said it was waiting for the release of all the data from the trial before it would consider giving up on Trasylol (aprotinin) but they have just been published in The New England Journal of Medicine and make for miserable reading.

In the trial of 2,331 high-risk cardiac patients undergoing heart surgery, Trasylol was compared with two lysine analogues Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid). The rate of death from any cause for Bayer’s drug was 6% versus 3.9 % and 4% percent for the other two respectively. This represents a 53% of relative risk of dying, noted co-principal investigator Paul Hebert of Ottawa Hospital, which means that for every 50 patients treated with aprotinin, one would die.

The BART authors noted that “in our study, the use of aprotinin did not significantly increase the risk of renal failure or the need for postoperative renal replacement”. However they concluded that “despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend” associated with Trasylol as compared with the lysine analogues “precludes its use in patients undergoing high-risk cardiac surgery”.

"End of the aprotinin story"
In a related editorial piece, Wayne Ray and Michael Stein of Vanderbilt University in Tennessee wrote that the conventional wisdom has been that aprotinin was most beneficial in high-risk surgeries that were likely to cause increased blood loss. However, “it is precisely in this population that BART provides convincing evidence as to the superiority of the lysine analogues”, they say, adding that “although the existence of a class of patients who would benefit from aprotinin is not impossible, it seems highly unlikely”. They conclude by saying that “thus, in all likelihood, this is the end of the aprotinin story”.

Just as the study was released, the US Food and Drug Administration said it had been informed that Bayer is removing remaining supplies of Trasylol from the US market and access will be limited to investigational use and for certain patients who have no alternatives.

The Trasylol saga has been a lengthy one. In October 2006, Bayer acknowledged that it failed to keep the FDA informed of data that could have had a bearing on the outcome of an advisory panel meeting looking at the safety of the drug. This was followed in December 2006 by yet another FDA review which changed the label on the drug to highlight the possible risk of kidney damage associated with taking it. However in September 2007, the agency’s Cardiovascular and Renal Drugs and the Drug Safety and Risk Management Advisory Committees voted 15 to one to keep Trasylol on the market, despite the potential health risks.

Bayer said that it needs to continue to carefully review the NEJM articles and later the underlying data on which the authors have based their conclusions before deciding how to proceed. However, given that the direct pharmacy cost of aprotinin for a four-hour cardiac procedure has been reported to be more than $1,400, as compared with less than $4 for aminocaproic acid, the end seems nigh.