Controversy Surrounding Trasylol (Aprotinin Injections)

Trasylol (Aprotinin Injections) Attorneys

Controversy Surrounding Trasylol (Aprotinin Injections): Study Indicates Possibility of Kidney Failure, Fatal Heart Attacks and Strokes

Trasylol, a drug manufactured by Bayer, has been used in the past in patients undergoing coronary artery bypass grafting (CABG) surgeries. Trasylol (also known as aprotinin injection) is an antifibronolytic agent injected during surgery to control blood loss and to prevent the need for blood transfusions.  Trasylol prevents bleeding during surgery by blocking a protein that dissolves blood clots, and the researchers hypothesize that this mechanism permits small clots that may have formed during the bypass procedure to persist and grow over time, resulting in fatal heart attacks and strokes.

The drug, derived from cattle lung tissue, was first approved by the FDA in 1993.  Trasylol was used in 200,000 bypass surgeries in 2006, a substantial decline from the estimated 600,000 patients who received the drug during bypass surgeries in 2005 and prior years.

trasyolIn January 2006, the Mayo Clinic published in the New England Journal of Medicine (NEJM) results of their study of 4,374 patients who had undergone bypass surgeries and received Trasylol. The Mayo study found that these patients had a more than 200% increased incidence of kidney failure and required dialysis after the surgery. In addition, the Mayo researchers noted a 55% increase in heart attacks and heart failure and 181% increase in strokes, coma, and encephalopathy in CABG patients who received Trasylol versus patients who received other types of antifibrinolytic therapies.  The NEJM study concluded that physicians should stop using Trasylol, as the alternative therapies were safer and less expensive. 

Another study published in January 2006 in Transfusion yielded similar results.  This second study followed 898 patients undergoing cardiac surgery and compared those who received Trasylol versus those receiving an alternative antifibronolytic drug.  Researchers concluded that patients receiving Trasylol had a 20% increased risk of heart attack and a 15% increased risk of stroke; in patients who had pre-existing kidney dysfunction, there was a 69% increased risk of renal failure.  (The incidences of adverse events in this study were smaller because it included fewer patients.)  Both of these early 2006 studies were conducted by non-profit, independent researchers without the financial support of Bayer, and both raised substantial basis for concern over Trasylol.

Months later, in fall 2006, the FDA issued a safety alert indicating that it was still reviewing these early studies, adverse events reported to the FDA, and other information in order to re-evaluate the safety of Trasylol.  At that time, physicians were urged to use caution and to monitor closely CABG patients receiving Trasylol for signs of toxicity reactions. Even though the FDA appears to have taken a strong stand, the safety alert was unusual in that it was highly critical of the two studies that had been published prior to that time - leaving patients and physicians confused. The FDA noted in its alert that pre-marketing clinical studies conducted by Bayer (which only included 3,000 patients) did not show any increased risk of kidney failure, heart attack, stroke or other serious complications except a questionable finding that Trasylol might cause complications that lead to blockages in the bypass graft.

The FDA decided to convene a panel of advisors to review the available data and to provide recommendations in the future about the fate of Trasylol and what information should be provided to physicians and patients.  The FDA has utilized Advisory Panels extensively in the past with mixed results.  Unfortunately, too often it is discovered that members of panels’ were paid consultants to the same manufacturers whose drugs were being reviewed. 

The Advisory Panel tasked with reviewing the safety of Trasylol reached a near-unanimous decision that was largely favorable to Bayer, despite compelling evidence that the drug posed very significant risks to patients. The Advisory Panel ultimately concluded that no change in the warnings for Trasylol was needed at that time, essentially ignoring the significant findings of the two studies from early 2006.

Just six days after the Advisory Panel had concluded its review and issued it decision, Bayer reportedly notified the FDA that, at the time of the Panel review, it had data on 67,000 patients documenting the exact risks of renal failure, stroke and heart failure that had been shown in the earlier studies.  Bayer has since admitted that it failed to disclose existence of the data to the FDA or the Panel.  Even more troubling is the fact that Bayer strongly advocated for the safety of its drug and attempted to discredit independent researchers who had uncovered safety risks - knowing all along that those researchers were, in fact, correct.   Three weeks after the Panel’s decision, Bayer also suspended three clinical studies involving Trasylol, but reassured the media that the trials were not stopped due to any safety concerns.

trasyolThe researchers at Mayo Clinic had offered the FDA “full access” to their data in advance of the Advisory Panel hearing, and had hounded the FDA for months to review the data.  The FDA, however, notified the Mayo Clinic researchers that a review of the Mayo data was not necessary prior to the Advisory Panel meeting.  Additionally, the Mayo Clinic researchers urged the FDA to reconvene the Advisory Panel so that it could conduct a proper (and independent) review of all of the data available so that “a course that puts patient safety at the forefront can be charted.” 

In a separate November 2006 letter to the NEJM, another Mayo Clinic researcher concluded:

“The FDA and its Advisory Committee should take a conservative, protective stance when independent evidence regarding drug safety presents itself.  Instead, they appear to be protecting the drug rather than the patient.”

Dr. Jerry Avorn of Harvard, also weighed in on the issue:

 “Many aspects of the aprotinin saga are familiar to observers of the drug evaluation process:  a product is approved because it is more effective than placebo, worries emerge about its safety, few or no adequately powered controlled trials are conducted to address these issues, and payers spend huge sums on the drug, despite the dearth of evidence that it is better than older, cheaper agents.  The healthcare system has a hard time performing drug-safety analyses, in large part because it relies on the pharmaceutical industry to conduct most research on the risks and benefits of medications.  It is naïve to expect companies to voluntarily fund studies that could sink lucrative products; the FDA lacks the regulatory clout to require them, and despite the $220 billion we spend on drugs each year, we apparently can’t find the resources to provide public support for these studies, even if the results could be of great clinical importance and save millions of dollars.” 

Dr. Avorn further commented:  “Bayer has admitted that its suppression of the study was a ‘mistake,’ but this is not the first time the company has behaved in this manner.  When Bayer was accused of hiding data unfavorable to its cholesterol-lowering drug cerivastatin (Baycol) before it was taken off the market in 2001, litigation uncovered a memorandum from a company executive arguing against performing a study of its risk. ‘If the FDA asks for bad news, we have to give,’ read the memo, ‘but if we don’t have it, we can’t give it to them.’” 

Did the FDA pull Trasylol from the market after so much controversy and in the face of damning safety information?

Did the FDA punish Bayer for its deceit?  

Sadly, the FDA took neither of these actions.

Instead, the FDA issued yet another Safety Alert to patients and physicians in December 2006, which strengthens the warnings regarding the risks of death, kidney failure, congestive heart failure, and stroke as noted in the studies in 2006 (and as noted in the data on 67,000 patients suppressed by Bayer).  The alert also indicates that studies of the drug before approval showed that some patients were experiencing anaphylactic and hypersensitivity reactions.    

In a sad postscript, another study was published in JAMA by the Mayo Clinic in February 2007, involving the review of medical records from 3,900 bypass surgery patients at 62 medical centers in 16 countries.  This study concluded that use of Trasylol increased patients’ long-term risk of dying by nearly 50% over patients who did not receive any drugs to prevent bleeding complications, and that Trasylol appears to have the ability to cause harm for five years after its use.  The study estimates that 10,000 patient deaths worldwide could have been prevented if Trasylol had not been used. Bayer, once again, has publicly criticized the validity of this study.  Dr. Mangano, author of two of the independent studies, commented:  “In good conscious, I could not administer Trasylol to [any] patients, especially given the availability of safer alternatives.  The least that should be done is to inform the patient that the risk of going on dialysis is increased two- to three-fold and there are alternatives.” 

On November 5, 2007, the FDA announced that it had reached an agreement with Bayer to suspend marketing of Trasylol.   Around that same time, results were published from a Canadian study that showed an increased risk of death associated with Trasylol, very similar to the results produced by previous studies.

A study published in May 2008 in the New England Journal of Medicine noted that the “study could have been done by the company [Bayer] five to ten years ago.” Finally, on May 14, 2008, not long after publication of the NEJM article, Bayer announced that it had completed the process of removing Trasylol from the shelves of hospitals and warehouses around the country and production and marketing of the drug worldwide was suspended. 

Following publicity over safety issues relating to Trasylol and its ultimate withdrawal from the market, multi-district litigation proceedings in federal court were established.  Judge David Middlebrooks from West Palm Beach in the Southern District of Florida presides over the cases.  Most of the cases pending in the MDL involve plaintiffs who suffered renal insufficiency, renal failure, or died after being exposed to Trasylol in connection with a bypass procedure.  As of January 2010, 644 individual lawsuits had been filed against Bayer by plaintiffs and their survivors who were injured by Trasylol.

If you or a loved one took Bextra and has suffered from heart attack, stroke, or renal injury, the attorneys at Searcy Denney Scarola Barnhart & Shipley represent unfortunate people fallen victims to Trasylol. Our attorneys are available to consult with you regarding your potential Trasylol claim. Please fill out our contact form, or call us to learn more and arrange for a confidential free consultation.

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