Washington, DCThe tragedy that is Trasylol and the scores of people who have died at the hands of the expensive anti-bleeding drug reads like the plot line of a bad movie. Only in this case, the villain doesn't get it in the end. At least, not yet. That payback may eventually be found in the courts of law as hundreds of lawsuits move forward.
In the meantime, we are left to marvel that sometimes truth is stranger than fiction, and how the warning bells that rang out at various times during this timeline of tragedy, were ignored—until it was too late for thousands.
December 30, 1993—Aprotinin, the scientific name for Trasylol, is awarded approval by the US Food and Drug Administration (FDA) to control excess bleeding in high-risk cardiac patients during surgery. It should be noted that some participants in clinical trials experienced kidney problems. Trasylol was approved anyway.
January 20, 2006—'Transfusion', a medical journal, publishes the findings of a study by Karkouti et al, which suggested an association between aprotinin and kidney problems amongst heart bypass patients.
January 26, 2006—Just six days later, the New England Journal of Medicine publishes the findings of yet another study, and this is the first time we hear the name of Dennis Mangano. The noted California-based researcher spent years studying aprotinin on behalf of a non-profit research institute, and concluded that Trasylol patients presented a 55 percent increase of heart failure and a whopping 181 per cent increase in stroke risk. Mangano's study also found that aprotinin patients were more than twice as likely to experience kidney failure, requiring dialysis.
February 8, 2006—The FDA issues a public health warning, and schedules an advisory committee meeting in seven months to vet the study findings, and decide Trasylol's ultimate fate. Unbeknownst to anyone, Trasylol manufacturer Bayer AG, headquartered in Germany, orders its own study in an attempt to verify, or disprove the findings of Mangano and Karkouti. That study is completed and delivered to Bayer in time for the advisory committee hearing.
September 21, 2006—The FDA convenes an Advisory Committee meeting to discuss Trasylol. Despite overwhelming evidence, the committee dismissed the findings of the two studies presented: Karkouti and Mangano et al, taking exception to the fact that Mangano's exhaustive effort was an observational study, and not the gold standard of a clinical trial. Based on that, the Committee voted to support the existing safety and efficacy position on Trasylol and strongly supported its continuance. The third study funded by Bayer and supporting the findings of the other two, was never presented at the hearing. The author of the Bayer study, horrified that his report was not brought forward at the Advisory Committee hearing, approached the FDA.
September 27, 2006—Bayer AG formally reveals to the FDA the existence of its own observational study, which, like the previous two, revealed the risk for stroke, congestive heart failure, kidney damage and death.
September 29, 2006—The FDA reveals publicly that Bayer had failed to disclose the study, and issues a safety warning to the medical community. Bayer explains the oversight as a regrettable human error.
October 13, 2006—Bayer suspends two employees in what appears, it has been reported, an attempt to explain and justify the oversight. Bayer suggests initially that the report was withheld because it was preliminary in nature, but later admitted that the study should have been presented to the Advisory Committee panel, and it undertook the suspension of two Bayer employees. The FDA issues a safety warning.
December 15, 2006—Trasylol product labeling is strengthened on the basis of an ongoing FDA review of Trasylol commenced at the beginning of the year. Trasylol was mandated to carry a black box warning for the potential of kidney damage, and its use limited to certain situations.
September 12, 2007—Yet another FDA Advisory Panel convenes, this time with all study material in hand. Incredibly, however, the Review Panel concludes that the benefits of aprotinin continue to outweigh the risks, and Trasylol is allowed to continue.
November 5, 2007—Trasylol is finally taken off the market after a Canadian clinical trial was halted due to an alarming death rate amongst aprotinin patients. The FDA, Health Canada as well as the German health authority combined to urge Bayer to pull Trasylol. Bayer agreed, subject to analysis of the Canadian BART findings. Dr. Dennis Mangano estimates that 1,000 lives were lost each month to Trasylol, and over 20,000 lives in the nearly two years it took to finally pull Trasylol from the market.
Lawsuits are expected to number into the thousands, as Trasylol patients and the families of those who have died litigate for pain, suffering and loss. Recently Trasylol patients have sued for financial hardship, given the cost of the drug. Trasylol came in at about $1000 per injection, vs. about $50 for alternatives.