May 15, 2008; Coalition against Bayer Dangers (Germany)

Heart drug's higher death risk detailed in study

Bayer AG is removing remaining supplies of its heart-surgery drug Trasylol from the market after a long-awaited study found it raised the risk of death compared to two alternatives.
The Coalition against Bayer Dangers has been warning of Trasylol´s risks for years. Please read the Coalition´s countermotion to Bayer´s shareholder meeting that took place in Cologne on April 25:
The medical doctor Professor Dr. Juergen Fischer already gave warnings concerning the dangers of TRASYLOL during the 1980's (see:

May 15, 2008; Toronto Star

Canadian medical report compared Bayer medication to others found to be safer

A massive Canadian study that caused a popular heart surgery drug to be pulled from the shelves last November has shown it increased the risk of death by 50 per cent over two rival medications.
Pharmaceutical giant Bayer AG voluntarily removed the anti-bleeding drug aprotinin, the generic name for Trasylol, from circulation when early results from the University of Ottawa-led study began to reveal its relative risks.
"The ... study will change the way heart surgery is done around the world," said Dr. David Mazer, an anesthesiologist at Toronto's St. Michael's Hospital and a co-author of the paper, the final draft of which was published online yesterday by the New England Journal of Medicine.
"As a result of the ... research, patients and their doctors can have that much more confidence going forward," Mazer told a media briefing in Ottawa this week.
"It was a bit of a surprise in seeing this," said Dr. Paul Hebert, a critical care physician at the Ottawa Hospital and a principal study investigator.
"We've ... shown, we think reasonably definitively, that (aprotinin) increases the risk of death as compared to two alternatives."
Hebert said the study showed that of "every 50 patients treated with aprotinin, one (more) patient would die" over those who received either of the other clotting drugs.
Bayer has never said whether it plans to try to resuscitate aprotinin. And even with the release of the trial data, it is hedging its bets.
"Bayer will continue to carefully review this article, the editorial and (when available) the underlying data on which the authors have based their conclusions and continue to discuss both the restricted access programs for Trasylol and the worldwide temporary marketing suspension of the drug with regulatory authorities," Bayer said in a prepared statement.
"When further conclusions are reached, Bayer will communicate publicly."
But an editorial in the journal predicted the drug is done.
"In all likelihood, this is the end of the aprotinin story," wrote Wayne Ray and Dr. Michael Stein, of the Vanderbilt University Center for Education and Research on Therapeutics in Nashville, Tenn.
The trial – known as BART for Blood Conservation using Antifibrinolytics in a Randomized Trial – took place in 19 centres across Canada, including St. Michael's.
It involved more than 2,400 patients.
The trial was halted last October, about two-thirds of the way through, after it began to show clearly that six per cent of patients who received aprotinin died within 30 days of surgery. This compared to just four per cent of patients who received either of the two alternate medications, tranexamic acid or aminocaproic acid.
"Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative trends in mortality associated with aprotinin use preclude its use in patients undergoing high-risk cardiac surgery," Hebert said, quoting from the paper.
"The risks of aprotinin are greater than its benefits," he continued.
Between one million and 1.25 million heart surgeries are performed worldwide each year, with about 25 per cent of these being "high risk." These include multiple bypass operations and valve work and generally require a bleeding-control drug to reduce the need for transfusions.
All three drugs help to stem such bleeding by inducing scablike clots along surgical incisions.
Researchers theorize aprotinin's superior ability to control bleeding – it was found to be about 20 per cent more effective than the others – may account for the greater risks it poses.
Earlier small-scale studies appeared to indicate that aprotinin was more dangerous than the other two medications, leading the U.S. Food and Drug Administration to issue a 2006 warning on its use.
Millions of patients would have been given the drug over the last decade, researchers say.
The BART study was sponsored by The Canadian Institutes of Health Research and the Ontario health ministry. (Joseph Hall , HEALTH REPORTER)

Oct. 1, 2008, The Madison Record

$2 million sought from Bayer over drug Trasylol

Two Illinois citizens have filed suit against Bayer, seeking more than $2 million and claiming a drug the company produced caused acute renal failure and led to the death of one of the complainant's spouses.

Both Gary Harms and Richard Kopsie were given the drug Trasylol during a coronary artery bypass graft surgery, according to the complaints filed Sept. 25 in St. Clair County Circuit Court.

The drug was approved by the Food and Drug Administration in 1993 for use in patients undergoing the same surgeries as Harms and Kopsie and those who are at an increased risk for blood loss, the suit states.

Harms underwent the surgery in which he was given the drug in 2005 at Des Peres Hospital in St. Louis, while Kopsie had his in August 1996 at Christian Hospital in St. Louis, the suit states.

The drug caused damage to both Harms's and Kopsie's kidneys, resulting in acute renal failure, Harms and Linda Kopsie claim.

Seth Sharrock Webb of Brown & Crouppen in St. Louis is representing the plaintiffs.

Dialysis is a mandatory treatment when patients suffer from acute renal failure, according to the complaint.

"It is a life support treatment," the suit states. "When healthy, the kidneys remove waste products from the blood and also remove excess fluid in the form of urine. Dialysis treatments have to duplicate both of these functions as dialysis and ultrafiltration."

Bayer issued no warnings until Dec. 15, 2006, on the increased risk of kidney failure because of the drug, despite the fact that by 2006 about 10,000 patients were on dialysis because of their exposure to Trasylol, the suit claims.

It also continued to market the drug until December 2006, even after the company knew the risks associated with it, according to the complaint.

By Nov. 5, 2007, Bayer announced a worldwide suspension of the marketing of Trasylol, and it remains off the market today, the suit states.

Richard Kopsie died on March 23, 2003, at the age of 53 as a result of Bayer's negligence, Linda Kopsie claims.

Before his death, Richard sustained injury, incurred medical costs, suffered from disability and a diminished ability to enjoy life and experienced pain and suffering, according to the complaint.

Linda claims she and Richard's three adult children sustained a loss of companionship, society and consortium because of his death.

She also claims she was responsible for funeral and burial costs.

Harms has suffered physical personal injury, medical expense, loss of consortium, services, love and affection, permanent loss of an important bodily function, permanent impairment of the ability to enjoy life and financial expenses since he was given the drug, the suit states.

He also claims he has sustained emotional and mental distress and anxiety.

Bayer was negligent because it continued to market the product, failed to warn the FDA of safety facts regarding the drug and failed to supply appropriate warnings for the drug, even though it should have known Trasylol's dangerous side effects, according to the complaint.

It also failed to perform adequate testing that would have revealed the drug's dangerous side effects, Linda and Harms claim.

In her 22-count suit, Linda Kopsie is seeking a judgment in excess of $1.1 million, plus costs and attorney's fees.

In his 11-count suit, Harms is seeking a judgment in excess of $550,000, plus costs and attorney's fees. By Kelly Holleran

Canadian Medical Association Journal, news release, Dec. 2, 2008

Another Study Warns of Risk From Cardiac Surgery Drug

A new study casts more doubt on the safety of the drug Trasylol (aprotinin), used to limit bleeding in patients undergoing surgery.
Trasylol is already the subject of controversy in the United States, where it was removed from the market in 2007.
In the new study, Canadian and Australian researchers reviewed findings from 49 randomized clinical trials. They concluded that Trasylol posed a higher risk of death for patients than other anti-bleeding drugs, called lysine analogues.
While Trasylol was somewhat more effective at controlling blood loss and transfusions than lysine analogues, its higher risk of death and significantly higher price are deterrents to its use, said the authors. They recommended tranexamic acid or aminocaproic acid as alternatives to prevent blood loss during surgery.
"Lysine analogues are almost as effective as aprotinin in controlling blood loss, are cheaper, and appear not to increase mortality," concluded Dr. David Henry and his co-authors of the study, which will be published in the Jan. 20 issue of the Canadian Medical Association Journal.
The findings were released early in advance of a Health Canada expert advisory panel meeting scheduled for Wednesday. The panel is expected to make a decision about the use of aprotinin.
The review included new information from the Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) study published by the New England Journal of Medicine earlier this year. That study found that patients treated with aprotinin were 53 percent more likely to die than those treated with two similar drugs, Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid). The death rates were 6 percent, 3.9 percent and 4 percent, respectively.
Due to the significant risk of death associated with Trasylol, the BART study was stopped in October 2007, before the schedule completion date.
In November 2007, Trasylol manufacturer Bayer AG suspended the drug's marketing in the United States after the preliminary results from the BART trial were released. Bayer removed all remaining stocks of the drug from the U.S. market earlier this year. However, the German drug maker continues to sell Trasylol in some areas of the world.
Trasylol has been on the market since 1987 and widely used. At the time of the BART study's release, one expert questioned why the truth about the dangers of the drug took so long to come out and how many patients may have died "because of this misadventure in therapeutics?"
"Did the clinical community accept it too readily? Was the manufacturer not willing to do the appropriate trials?" asked Dr. Eric J. Topol, director of the Scripps Translational Science Institute and dean of the Scripps School of Medicine.
The U.S. Food and Drug Administration is high on the blame list, Topol told HealthDay.
"The FDA has to be considered part of the problem," he said. "Why weren't trials like this part of the early approval process, rather than getting the data many years later?"
More information
The U.S. National Heart, Lung, and Blood Institute has more about coronary artery bypass surgery.