Bayer yanks aprotinin off the market pending analysis of BART

Shelley Wood

November 05, 2007

Leverkusen, Germany and West Haven, CT - Aprotinin (Trasylol) manufacturer Bayer has suspended worldwide marketing of the drug, pending final results from the Canadian Blood Conservation Using Antifibrinolytics Trial (BART). As reported by heart wire , enrollment in BART, a high-risk cardiac surgery trial, was halted in mid-October after more patients receiving aprotinin died within the first 30 days of the trial, as compared with patients taking epsilon-aminocaproic acid or tranexamic acid. A company press release notes that while bleeding rates were reduced in the aprotinin arm of the trial—the hypothesized benefit of the drug in this study—mortality "almost reached conventional statistical significance," which was enough for the data and safety monitoring board to suggest the trial be stopped.

The company made the decision to yank aprotinin after consulting with the German Federal Institute for Drugs and Medical Devices (BfArM), the FDA, Health Canada, and other health authorities, a Bayer press release states.

Aprotinin is currently approved for preventing perioperative blood loss and cutting the need for transfusions during pump-supported CABG surgery in high-risk patients. But it has faced a rocky ride since a phase 4 study came out in early 2006 indicating that despite 13 years on the market, the drug appeared to increase the risk of serious end-organ damage, particularly renal failure. The FDA subsequently issued a public-health advisory alerting doctors to the higher risk of renal failure, MI, and stroke. Later last year, an FDA advisory panel ruled that aprotinin was safe if used as indicated, only to learn of additional data that might have swayed its decision. Meeting again a year later, the FDA panel once more recommended that aprotinin stay on the market with stronger warnings, and just last month, a large meta-analysis of randomized trials indicated that aprotinin does not raise the risk of operative thrombosis or death.

Commenting on Bayer's decision to heart wire , FDA advisory panel member Dr Michael Lincoff (Cleveland Clinic, OH)—emphasizing that his views were his own, not the panel's or the FDA's—said he was not surprised by the latest turn of events.

"At the time of the last meeting, I, among others, was concerned, but still felt that, since the only data we were looking at were observational, it still didn't reach the level where one would argue to remove the drug from the market, although I and others expressed very strong concerns that they needed to do a randomized trial of adequate size in the current era of contemporary practice to see whether these risks really were there."

At that time, FDA advisors were worried that BART might not have been adequately powered to pick up important safety signals; Bayer's announcement today suggests that that was not the case. While he did not have specific numbers, Lincoff suggested that the excess risk among aprotinin-treated patients in BART was as high as 40%.

"If that's the case, that's about the same as what we've seen with some of the observational data," Lincoff said. "So I think it's either going to eliminate the use of the drug entirely or reduce it dramatically to a very select group of patients who are at very high risk of bleeding."

For now, Bayer is calling the marketing suspension "temporary" and says it is in the process of collecting data from centers across Canada. It intends to perform a full data analysis before making a final decision on the drug—a process that will take eight weeks or longer, the press release notes.

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