Trasylol: Pivotal Study Could Have Happened Sooner

New York, NYOne of the lead authors of a pivotal Canadian study that most experts say will spell the end of Trasylol, has suggested that Bayer AG could have undertaken a similar study ten years ago. In that time, thousands have died.

Dr. Paul Hebert, a critical care physician at Ottawa Hospital in Canada's capitol city told the Wall Street Journal recently that "this study could have been done by the company five, to ten years ago," amidst previous reports linking Trasylol with heart and other problems—not to mention saving patients and the health-care system a ton of money, given the spread in cost between Trasylol and alternatives.

A dose of aminocaproic acid, widely felt as equally effective in mitigating bleeding during cardiac surgery but without the risks associated with Trasylol, comes in at about $4 per dose.

Compare that to $1400 per dose for Trasylol. Little wonder, at the Bayer AG Annual Stockholders Meeting in Leverkusen, Germany back in April that Bayer Chairman Werner Wenning announced that 2007 was Bayer's "most successful year to date."

Trasylol had been under suspicion for several years, with various red flags revealed in recent months amidst the tidal wave of press accompanying the Fall of Trasylol.

Then along came noted researcher Dennis Mangano who, working on behalf of a non-for-profit institute, released his exhaustive observational study suggesting that Trasylol proved a serious risk, while no more effective than less-expensive alternatives. Soon to be facing an expert panel debating the merits of Trasylol, Bayer commissioned its own observational study in an effort to disprove Mangano's findings.

When the new study was found to support, and agree with the conclusions of the Mangano study, Bayer was faced with appearing before a US Food and Drug Administration (FDA) expert panel with at least two studies that challenged the safety of Trasylol.

Interestingly, the study commissioned by Bayer and received by Bayer prior to the FDA hearing, never made it to the FDA hearing. When called on the 'oversight' later, Bayer claimed that a grievous human error had been made, and disciplined two employees.

The outcome of the hearing, of course, went in Bayer's favor. Panelists were at odds with the fact Mangano's study was observational and not a clinical trail, long considered the gold standard. The availability of one other small study, which also supported Mangano's findings, was not enough for the panel to recommend Trasylol be taken off the market.

That was in September 2006. A year later the exercise was repeated, only now with the additional study that was missing in action a year earlier. And yet somehow, in spite of mounting evidence, the FDA panel concluded that the benefits of Trasylol continued to outweigh the risks.

The so-called BART trial in Canada changed all that. First, it was a true clinical trial, where Trasylol was compared with two other drugs. Second, it was publicly funded (and therefore no chance of bias), and fairly in-depth, involving 2,331 patients in 19 Canadian cardiac centers. The study found that Trasylol was marginally effective at decreasing massive bleeding, but the benefit did NOT outweigh the substantial risks. Of the 108 patients who expired, the group experiencing "cardiogenic shock, right ventricular failure, congestive heart failure or myocardial infarction was higher in the aprotinin (Trasylol) group than in the other two groups."

Finding that Trasylol was associated with a 54 percent increase in the relative risk of death, the BART trial was halted. Bayer AG, the German-based pharmaceutical giant, responded by calling a halt to the marketing of Trasylol. However, the drug was never banned, or recalled. It wasn't until the BART trial findings were published in the New England Journal of Medicine last month—amounting to yet another nail in the Trasylol coffin—that Bayer decided to recall any remaining vials of Trasylol from hospitals, physicians and other supply chains.

However, Bayer has not backed away from its assertion that the marketing suspension of Trasylol was anything but temporary, and the drug has not been banned. It is still approved for limited use by the FDA, albeit with cautions.

Meanwhile Dr. Hebert, of Ottawa Hospital, says that clearly Trasylol should not be used for high-risk cardiac surgery patients, together with the comment that the manufacturer could have conducted a detailed clinical trial akin to BART five or ten years ago when various red flags were emerging, but did not.

Mangano asserts that thousands of lives would have been lost needlessly in that time, while Bayer was happily accepting $1400 per dose of Trasylol, and watching its anti-bleeding drug progress towards a billion-dollar annual sales plateau.

That won't be happening now, obviously. However, in spite of the Trasylol fallout, 2007 was a good year for Bayer AG financially. A record-breaking year.

Patients who have been harmed, or the families of patients who have died from complications brought on by Trasylol, may want to heed that observation in concert with their Trasylol lawyer.