Yourlawyer.com (Trasylol News)

Trasylol Lawsuit Claims Bayer Failed to Warn of Side Effects

Fri, 04 Sep 2009 00:00:00 -0700

Bayer has been sued over Trasylol, a drug used to prevent bleeding during heart bypass surgery that was withdrawn from the market in May 2008. According to MadisonRecord.com, the lawsuit alleges that Bayer did not warn of the possible serious side effects linked to Trasylol.

Trasylol was approved by the US Food & Drug Administration (FDA) 1993 and, before it was withdrawn, had been used in a third of all heart surgery patients in the US. However, Trasylol has been the subject of concern for years, and its safety has been reviewed several times. In October 2007, the Canadian Data Safety Monitoring Board stopped a Trasylol trial – known as the BART clinical study – after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany.

Bayer decided to take Trasylol off the market for good after an analysis of the Canadian study was published in a May 2008 issue The New England Journal of Medicine. The analysis found that of the 2,331 people enrolled in the Canadian study, the death rate among Trasylol patients was 6 percent, while the rate for those being treated with other drugs – namely Amicar or Cyklokapron – was 4 percent. That represented an increased death rate of 53 percent for Trasylol patients, which translates to one extra death for every 50 patients treated with Trasylol.

The latest Trasylol lawsuit was filed in Illinois' St. Clair County Circuit Court by a man and woman who claim their use of Trasylol led to renal damage, renal insufficiency and multi-system organ failure. According to the complaint, when Trasylol first came to market, Bayer provided no warnings about its link to renal toxicity. The side effect first was revealed in an online "Transfusion" article dated Jan. 20, 2006, according to the complaint. Another study was published in the "New England Journal of Medicine" on Jan. 26, 2006, reporting Trasylol's association with serious renal toxicity and ischemic events.

That prompted the FDA to take another look at the drug, but an agency advisory panel it warnings on Trasylol did not need to be strengthened. However, according to the complaint, a Bayer-paid study of 67,000 patients had confirmed that Trasylol increased the risk of renal failure, heart attack and stroke, and suggested that those treated with the drug faced an increased risk of death, kidney failure and congestive heart failure. The lawsuit alleges that Bayer knew of these study results, but didn't disclose them to the FDA. A Harvard researcher who had worked on the study informed the FDA of its findings just after the advisory panel made its recommendation.

In December 2006, the FDA finally did direct Bayer to update the Trasylol label to include a warning that it increases the risk of kidney damage. The revised label also specified that the drug should be given only to patients who are at an increased risk for blood loss and blood transfusion.

Another Trasylol Study Finds Cheaper Drugs Less Risky

Thu, 04 Dec 2008 00:00:00 -0800

Another study is questioning the safety of Trasylol (aprotinin). Trasylol, a drug made by Bayer for use in cardiac surgery, was withdrawn from the market last year amid safety concerns.

Trasylol was approved by the US Food & Drug Administration (FDA) in 1993 and, before it was withdrawn, had been used in a third of all heart surgery patients in the US. However, Trasylol has been the subject of concern for years, and its safety has been reviewed by the FDA several times.

Last October, the Canadian Data Safety Monitoring Board stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany.

Bayer decided to take Trasylol off the market for good after an analysis of the Canadian study was published this past May in The New England Journal of Medicine. The analysis found that of the 2,331 people enrolled in the BART study, the death rate among Trasylol patients was 6 percent, while the rate for those being treated with other drugs known as lysine analogues - namely tranexamic acid or aminocaproic acid - was 4 percent. That represented an increased death rate of 53 percent for Trasylol patients, which translates to one extra death for every 50 patients treated with Trasylol.

According to this new study, Trasylol is much riskier than less expensive alternatives. To reach that conclusion, researchers at the Institute for Clinical Evaluative Sciences (ICES) in Toronto reviewed 49 randomized trials comparing Trasylol to tranexamic acid or aminocaproic acid. The review, which appears in the Canadian Medical Association Journal, included new information from the earlier BART study.

"Compared with aprotinin, lysine analogues are almost as effective, are cheaper and do not appear to increase mortality," the authors concluded after reviewing the randomized trials. "Either tranexamic acid or epsilon aminocaproic acid should be recommended to prevent bleeding after cardiac surgery," the team wrote.

Trasylol Named in Two Lawsuits

Fri, 10 Oct 2008 00:00:00 -0700

Trasylol, Bayer AG's now-withdrawn anti-bleeding medication, is the subject in two Illinois lawsuits. One of the plaintiffs claims Trasylol was the cause of her husband's death, and the other alleges the drug caused him to suffer acute renal failure. Bayer permanently withdrew Trasylol from the market in May 2008, after a study found that it increased patients' risk of death by more than 50 percent.

Trasylol was approved by the US Food & Drug Administration (FDA) 1993 and, before it was withdrawn, had been used in a third of all heart surgery patients in the US. However, Trasylol has been the subject of concern for years, and its safety has been reviewed several times. Last October, the Canadian Data Safety Monitoring Board stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany.

Bayer decided to take Trasylol off the market for good after an analysis of the Canadian study was published in a May issue The New England Journal of Medicine. The analysis found that of the 2,331 people enrolled in the Canadian study, the death rate among Trasylol patients was 6 percent, while the rate for those being treated with other drugs - namely Amicar or Cyklokapron - was 4 percent. That represented an increased death rate of 53 percent for Trasylol patients, which translates to one extra death for every 50 patients treated with Trasylol.

According to complaints filed last month in St. Clair County Circuit Court, both Gary Harms and Richard Kopsie were given Trasylol during a coronary artery bypass graft surgery. 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. Both required dialysis treatment. Kopsie died on March 23, 2003, at the age of 53 as a result of Bayer's negligence, his widow, Linda Kopsie, claims.

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

Linda Kopsie is seeking a judgment in excess of $1.1 million, plus costs and attorney's fees. Harms is seeking a judgment in excess of $550,000, plus costs and attorney's fees.

Trasylol Gone for Good

Thu, 15 May 2008 00:00:00 -0700

Trasylol is being removed from the market for good. Bayer AG had suspended marketing of Trasylol, a drug used to prevent bleeding during heart surgery, in November, after a clinical trial found patients treated with Trasylol were dying at higher rates than others. Now, the results of that trial are in, and the death risk has been confirmed. Yesterday, Bayer notified the Food & Drug Administration (FDA) that it was removing the remaining Trasylol stock from the market.

Trasylol was approved in 1993 and has been used in a third of all heart surgery patients in the US. However, Trasylol has been the subject of concern for years, and its safety has been reviewed several times. Last November, the Canadian Data Safety Monitoring Board had stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany.

Now, an analysis of that Canadian trial is set to be published next week. According to media repots, the study found Trasylol increased chances of death by 54 percent, compared to two much-cheaper drugs. Six percent of the Trasylol patients died within 30 days of surgery, compared with 4 percent who got either Amicar or Cyklokapron, despite a slightly lower percentage of the Trasylol patients suffering from massive bleeding or needing transfusions. The researchers found those who died in the Trasylol group had a much higher proportion of heart complications after surgery, including heart attacks.

The Canadian study is just one of several that have illustrated the deadly consequences of Trasylol, and many health advocates believe it should have been removed from the market years ago. In September 2006, Dr. Dennis Mangano presented a study he authored to the FDA which found that Trasylol increased the risk of kidney failure requiring dialysis, as well as death. Ealier this year, Mangano told “60 Minutes” the he believes Trasylol should have been taken off the market when he published his study in 2006. Between the study’s publication and November 2007, when Bayer removed the drug, “There were approximately 431,000 patients who received the drug,” Mangano. “As I calculated, 22,000 lives could have been saved. It’s about a 1,000 lives per month.”

Even Bayer had evidence of Trasylol's death risk, but withheld it for a time. Bayer executives attended Mangano’s presentation in order to defend Trasylol. What they did not tell the FDA was that their own Trasylol study, known as the I3 drug report, confirmed Mangano’s findings. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes. Bayer claims that this was an oversight, as the company’s management was not informed of the report until after the safety review.

In December 2006, the FDA updated the Trasylol label to include a black box warning - the agency’s strictest safety notice - stating that the drug placed patients at a high risk of kidney failure. Then in September 2007, even while agreeing with the assessment that Trasylol had a high risk of causing fatal side-effects, an FDA advisory panel voted that Trasylol should stay on the market.

Bayer faces nearly 80 lawsuits over Trasylol. As late as February, the company had maintained that it would eventually return Trasylol to the market. Yesterday, Bayer changed its tune, and said it was removing Trasylol supplies from all countries where it remained in the supply chain, except where local authorities wanted to keep it in the market for special access programs.

Trasylol Named in 78 Lawsuits, Bayer Says

Mon, 28 Apr 2008 00:00:00 -0700

Bayer AG has been hit with 78 lawsuits over the drug Trasylol. In November, Bayer suspended Trasylol sales after a Canadian study linked it to a higher risk of death.

Trayslol was approved in 1993, and was used to prevent bleeding during open heart surgeries. Since its approval, about a third of all heart surgery patients in the US have been treated with Trasylol. Trayslol was the subject of several Food & Drug Administration (FDA) safety reviews before it was finally pulled from the market last year.

In December 2006, following an advisory panel meeting that September, the FDA updated the Trasylol label to include a black box warning - the agency’s strictest safety notice - stating that the drug placed patients at a high risk of kidney failure and death. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries.

Another FDA advisory panel that met in September 2007 agreed with the assessment that Trasylol had a high risk of causing serious side-effects, and it recommended that Trasylol undergo further clinical testing. However, the FDA panel also voted that Trasylol should stay on the market. Then in November, the Canadian Data Safety Monitoring Board had stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany.

Earlier this year, Trasylol researcher Dr. Dennis Mangano told the television show "60 Minutes" that studies had indicated Trasylol was dangerous years before it was removed from the market. In September 2006, Dr. Mangano presented a study he authored to the FDA which found that Trasylol increased the risk of kidney failure requiring dialysis, as well as death.   Mangano told “60 Minutes” that he believes Trasylol should have been taken off the market when he published his study in 2006. Between the study’s publication and November 2007, when Bayer removed the drug, “There were approximately 431,000 patients who received the drug,” Dr. Mangano said. “As I calculated, 22,000 lives could have been saved. It’s about a 1,000 lives per month.”

Bayer executives attended Mangano’s presentation in order to defend Trasylol. What they did not tell the FDA was that their own Trasylol study, known as the I3 drug report, confirmed Mangano’s findings.   That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes. Bayer claims that this was an oversight, as the company’s management was not informed of the report until after the safety review.

But even after learning of the I3 drug report, the FDA allowed Trasylol to remain on the market. It wasn't until the BART study that the FDA and Bayer finally moved to protect patients from this dangerous drug. But Bayer still hasn’t given up on Trasylol.   According to “60 Minutes”, the company is still defending Trasylol. Bayer sent a letter to “60 Minutes” claiming that “the available data continue to support a favorable risk-benefit profile for Trasylol when used according to labeling.” According to the program, Bayer plans to assess whether Trasylol can be remarketed after further research. Bayer also says it will "vigorously defend" itself against Trasylol lawsuits.

More Trasylol Studies -- One Previously Withheld by Bayer -- Confirm Death Risks

Thu, 21 Feb 2008 00:00:00 -0800

Two more Trasylol studies have concluded that heart surgery patients are more likely to die if treated with the defective drug. Trasylol, manufactured by Bayer AG, was the subject of several Food & Drug Administration (FDA) safety reviews before it was finally pulled from the market last year. One of the newly released studies was completed prior to a September 2006 FDA advisory panel meeting on Trasylol, but was never submitted by Bayer to the FDA.   Bayer suspended sales of Trasylol at the request of the FDA after Canadian health officials halted a portion of a clinical trial after it was determined that patients in the study treated with Trasylol where more likely to die.

Trasylol was approved in 1993, and was used to prevent bleeding during open heart surgeries. Since its approval, about a third of all heart surgery patients in the US have been treated with Trasylol. In December 2006, following the September meeting, the FDA updated the Trasylol label to include a black box warning - the agency’s strictest safety notice - stating that the drug placed patients at a high risk of kidney failure and death. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries.

Another FDA advisory panel that met in September 2007 agreed with the assessment that Trasylol had a high risk of causing serious side-effects, and it recommended that Trasylol undergo further clinical testing. However, the FDA panel also voted that Trasylol should stay on the market. Then in November, the Canadian Data Safety Monitoring Board had stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany.

Now two more studies have added to fears that Trasylol is dangerous. Bayer funded one of the two new studies, and had the preliminary results ready before the September 2006 federal hearing on the drug’s safety, but did not present them at the meeting.   Bayer has defended its actions by saying the study results at the time where only preliminary and the study itself was flawed. The Bayer study looked at more than 78,000 patients nationwide in a period from January 1, 2003 to March 31, 2006. After adjusting for other factors, the researchers found the risk of death after surgery was 64 percent higher in the Trasylol group than in those taking a comparison drug.

The second Trasylol study looked at more than 10,000 patients who had bypass surgeries at Duke University Medical Center from 1996 through 2005. It found that 6.4 percent of patients who were given Trasylol died within 30 days of the surgery, a rate nearly 2½ times higher than patients who got another drug or who received no treatment for excessive bleeding. At one year after surgery, almost 16 percent of Trasylol patients had died — again, roughly 2½ times higher than the other two patient groups.

A spokesperson for the consumer advocacy group Public Citizen told the Associated Press that the latest Trayslol studies are convincing confirmation of the drug’s dangers. “I just don’t know how much further evidence you need,” said Dr. Sidney Wolfe.   Wolfe added that federal health officials should pursue criminal charges against Bayer for withholding information from its own study from the FDA panel in 2006.

FDA Trasylol Failure Could Have Killed Thousands, Researcher Says

Fri, 15 Feb 2008 00:00:00 -0800

Trasylol, a defective drug manufactured by Bayer AG, may have killed 22,000 people before it was pulled from the market last year. Trasylol was withdrawn in November at the request of the Food & Drug Administration (FDA) after an observational study linked the medicine to kidney failure requiring dialysis and increased death of those patients. But a researcher who presented a Trasylol study to the FDA in 2006 told the TV program “60 Minutes” that thousands of lives would have been saved if the FDA had acted sooner.

Trasylol is a drug used to prevent bleeding during heart bypass surgery, and before it was removed from the market, about a third of all bypass patients had received Trasylol. In September 2006, Dr. Dennis Mangano presented a study he authored to the FDA which found that Trasylol increased the risk of kidney failure requiring dialysis, as well as death. Mangano told “60 Minutes” the he believes Trasylol should have been taken off the market when he published his study in 2006. Between the study’s publication and November 2007, when Bayer removed the drug, "There were approximately 431,000 patients who received the drug," Mangano. "As I calculated, 22,000 lives could have been saved. It’s about a 1,000 lives per month.”

Bayer executives attended Mangano’s presentation in order to defend Trasylol. What they did not tell the FDA was that their own Trasylol study, known as the I3 drug report, confirmed Mangano’s findings. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes. Bayer claims that this was an oversight, as the company’s management was not informed of the report until after the safety review.

The chairman of the FDA committee that held that meeting, Dr. William Hiatt, told “60 Minutes” that he would have voted to remove Trasylol from the market if he had known about Bayer’s study. He also took issue with Bayer's failure to disclose it. "I thought it was unusual. I thought it was truly inappropriate,"

But even after learning of the I3 drug report, the FDA allowed Trasylol to remain on the market. In December 2006, the FDA updated the Trasylol label to include a black box warning - the agency’s strictest safety notice - stating that the drug placed patients at a high risk of kidney failure. Then in September 2007, even while agreeing with the assessment that Trasylol had a high risk of causing fatal side-effects, an FDA advisory panel voted that Trasylol should stay on the market.

It wasn’t until November 2007, when the Canadian Data Safety Monitoring Board had stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. While the patients in the Trasylol clinical trial did experience less serious bleeding, there were more deaths due to hemorrhage in the Trasylol group. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US at the FDA’s request.

But Bayer still hasn’t given up on Trasylol. According to “60 Minutes”, the company is still defending Trasylol. Bayer sent a letter to “60 Minutes” claiming that “the available data continue to support a favorable risk-benefit profile for Trasylol when used according to labeling." According to the program, Bayer plans to assess whether Trasylol can be remarketed after further research.

Trasylol Drug Combo Linked to Deaths

Tue, 12 Feb 2008 00:00:00 -0800

A new Trasylol study is shedding more light on possible reasons behind the drug’s higher-than normal death rate. According to British researchers, while use of the clotting drug aprotinin—known as Trasylol—appears safe during on-pump cardiac surgeries, it appears that combining it with angiotensin-converting enzyme inhibitors—or ACE inhibitors—during off-pump cardiac surgeries shows a significant risk of post-operative kidney dysfunction. Researchers analyzed 9,875 cardiac surgery patients, most of who (5,434) had on-pump cardiac surgery, meaning their hearts were stopped and they were hooked up to a heart-bypass machine during surgery. The other patients had off-pump cardiac surgery, in which surgeons operated on their beating hearts.

Trasylol is used to reduce perioperative blood loss and the need for blood transfusion in those patients undergoing cardiopulmonary bypass during coronary artery bypass graft surgery and who are at an increased risk for blood loss and blood transfusion. ACE inhibitors are used in the treatment of hypertension and congestive heart failure.

The study was prompted by previous research that noted an association between use of aprotinin and renal failure. Drug maker Bayer voluntarily suspended worldwide marketing of aprotinin after preliminary findings from a Canadian study (BART) suggested the drug increased the risk of death. That study was a planned analysis and revealed reduced bleeding, but also a mortality increase that nearly reached conventional statistical significance for patients receiving Trasylol. That trial was halted in October 2007.

Among those who underwent on-pump surgery, there was no significant association between Trasylol and post-operative renal dysfunction, regardless of ACE inhibitor use; however, Trasylol was associated with a more than two-fold increased risk of renal dysfunction among the 848 patients who had off-pump cardiac surgery and who received both Trasylol and ACE inhibitors. "We recommend that it might be beneficial for patients to discontinue any use of an ACE inhibitor before elective off-pump surgery, particularly patients with a history of renal impairment," wrote Dr. Ronelle Moulton and Kai Zacharowski, from the department of anesthesia, Bristol Royal Infirmary, United Bristol Healthcare Trust. Moulton and Zacharowski’s study was published in this week's issue of The Lancet. A complete analysis of the BART findings will not be known for some time, Dr. Derek Hausenloy, of The Hatter Cardiovascular Institute, University College London Hospital and Medical School, and colleagues wrote in an accompanying comment.
"While waiting for that analysis, the use of Trasylol in the U.S. and in some European countries has been necessarily restricted, with the consequence that some high-risk patients having cardiac surgery might not receive optimum therapy," Hausenloy and colleagues noted.

Bayer suspended global Trasylol marketing following consultation with the German Federal Institute for Drugs and Medical Devices (BfArM), the U.S. Food and Drug Administration (FDA), Health Canada, and other health authorities and until final results from the Canadian BART trial can be compiled, received, and evaluated. The BART study is an independent randomized, controlled trial being conducted in high-risk cardiac surgery patients. FDA, Health Canada, and other health authorities have indicated a desire to work with Bayer on a program in which physicians might receive Trasylol for treatment of certain surgical patients with medical need during the suspension period.

Trasylol Sales Suspended After Canadian Study Links Drug to Sudden Death Risk

Mon, 26 Nov 2007 00:00:00 -0800

Trasylol, a drug used to prevent bleeding during heart surgery, was removed from the market by Bayer AG earlier this month after it was linked to a risk of sudden death. According to the Food & Drug Administration, Trasylol may have been responsible for more than 200 fatalities.

The Canadian Data Safety Monitoring Board had stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study's Trasylol patients was nearing "statistical significance". While the patients in the Trasylol clinical trial did experience less serious bleeding, there were more deaths due to hemorrhage in the Trasylol group. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany.

Trasylol was approved in 1993 and since then, several studies have found evidence of dangerous side effects associated with it. Last year, a study published in the Journal of the American Medical Association found that Trasylol increased the risk of death by about 50 percent for some patients. A second 2006 Trasylol study, known as the I3 drug report, suggested that Trasylol increased the risk of a patient dying by 54 percent. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes.

In December, the FDA updated the Trasylol label to include a black box warning - the agency's strictest safety notice - stating that the drug placed patients at a high risk of kidney failure. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries. In September, an FDA advisory panel agreed with the assessment that Trasylol had a high risk of causing serious side-effects, and it recommended that Trasylol undergo further clinical testing. However, the FDA panel also voted that Trasylol should stay on the market.

Between 1993 and February 2006, the FDA received 235 reports "that noted death in patients who received Trasylol" to control bleeding during heart-bypass surgery. So far the FDA has been unable to confirm the exact number of deaths for the past 19 months. However, the number of Trasylol death reports was expected to jump during that period following several studies warning the drug could cause kidney damage, stroke and heart failure.

According to Bayer, once the complete BART dataset is available, the company will work with health authorities to evaluate whether these data have any impact on the positive benefit-risk assessment for Trasylol. At that time the temporary marketing suspension will be reevaluated.

Trasylol Deaths Exceed 200, FDA Says

Mon, 19 Nov 2007 00:00:00 -0800

Trasylol, a defective drug made by Bayer AG, may have killed more than 200 people, according to the Food & Drug Administration (FDA). Trasylol, used to prevent bleeding during heart surgeries, was pulled from the market earlier this month, after it was linked to an increased risk of death.

The FDA had asked Bayer to suspend sales of Trasylol, known generically as aprotinin, after a clinical trial involving the drug was halted. The Canadian Data Safety Monitoring Board had stopped the Trasylol trial after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. While the patients in the Trasylol clinical trial did experience less serious bleeding, there were more deaths due to hemorrhage in the Trasylol group. When news of the Canadian trial broke, the FDA initially issued guidelines that said doctors who were considering using Trasylol should be aware of the risks and benefits of the drug, as well as the accumulating data suggesting Trasylol increases the risk of death compared to other antifibrinolytic medications.   But a few days later, the FDA and Bayer agreed that sales of Trasylol would be suspended while the agency reviewed its safety.

Over the weekend, the “New York Post” published a report that Trasylol has been linked to more than 200 deaths. According to the newspaper, The FDA received 235 reports "that noted death in patients who received Trasylol" to control bleeding during heart-bypass surgery from 1993, when the drug was approved, through February 2006. The FDA was unable to confirm the exact number of deaths for the past 19 months, the newspaper said.   The number of Trasylol death reports was expected to jump during that period following several studies warning the drug could cause kidney damage, stroke and heart failure.

Trasylol was approved in 1993 and is used during heart bypass surgeries to prevent bleeding. Last year, a study published in the Journal of the American Medical Association found that Trasylol increased the risk of death by about 50 percent for some patients. A second 2006 Trasylol study, known as the I3 drug report, suggested that Trasylol increased the risk of a patient dying by 54 percent. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes.

In December, the FDA updated the Trasylol label to include a black box warning – the agency’s strictest safety notice – stating that the drug placed patients at a high risk of kidney failure. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries. In September, an FDA advisory panel agreed with the assessment that Trasylol had a high risk of causing serious side-effects, and it recommended that Trasylol undergo further clinical testing. However, the FDA panel also voted that Trasylol should stay on the market.

But the evidence of an increased death rate found by the Canadian Trasylol trial was more than the FDA could ignore, and the agency took the drastic step of asking Bayer to remove it from the market. It is not known when – or if – Bayer will be able to market Trasylol again.

Trasylol Pulled From World Market by Bayer AG

Wed, 07 Nov 2007 00:00:00 -0800

Trasylol, an anti-bleeding medication, was pulled from the market earlier this week following concerns that it put patients at a high risk of death. The German pharmaceutical firm Bayer AG announced that it would stop worldwide sales of Trasylol after a Canadian Trasylol study was suspended after a data analysis found that patients treated with Trasylol had higher risk of death than other patients in the trial. Trasylol is the trade name for aprotinin, approved by the FDA in 1993. Approximately 200,000 patients around the globe used the product last year, more than half of them in the United States. The drug decreases bleeding during surgery, making risky transfusions unnecessary. Worldwide sales so far in 2007 total approximately $135 million, according to Bayer, with $91 million of those sales within the U.S. Trasylol blocks the enzymes that dissolve blood clots.

Two other older drugs are also used for this purpose. A clinical study by the Ottawa Health Research Institute was evaluating Trasylol versus the other drugs in 3,000 valve-surgery and heart bypass patients. When the study indicated that the drug was more effective in stopping bleeding – but caused 50% more deaths than the other two alternatives due to hemorrhage – the Canadians halted the medical trial.

After a preliminary review of the Canadian findings, the U.S. Food and Drug Administration asked Bayer AG to stop selling the drug. Just a month ago, the FDA had recommended keeping Trasylol on the market, despite preliminary reports about serious side effects and potential increase in fatalities. The agency’s Dr. John Jenkins, who heads the FDA’s Office of New Drugs, denied that the earlier recommendation was a mistake, even though the regulatory group now says it “cannot identify a specific patient population where we believe the benefits of using Trasylol outweighs the risk.” Bayer is reported to have withheld an earlier unfavorable study from the U.S. agency due to a “regrettable human error.”

Bayer’s withdrawal of Trasylol coincided with the annual meeting of the American Heart Association (AHA) in Orlando, FL. Physicians attending the scientific gathering had mixed feelings about the drug’s withdrawal. The AHA spokesman Dr. Timothy Gardner said that Trasylol was “particularly useful for certain patients.” The drug’s official web page within the Bayer AG site claims that Trasylol “breaks the chain of events caused by bypass-induced SIRS (systemic inflammatory response syndrome).” An update on the same site announces Bayer’s suspension of sales around the world, but describes the suspension as “temporary.” Bayer AG is based in Frankfurt, Germany. Referring to the Canadian study, Bayer said it would “work with health authorities to evaluate whether these data have any impact on the positive benefit-risk assessment for Trasylol."

Trasylol to Undergo another FDA Safety Review After Canada Halts Clinical Trial

Mon, 29 Oct 2007 00:00:00 -0700

Trasylol will be the subject of yet another Food & Drug Administration (FDA) safety review, after a clinical trial involving the drug was halted because of indications that Trasylol increased patients’ risk of dying. Just last month, an FDA advisory panel had recommended that the clotting drug be allowed to remain on the market, despite the fact that it was linked to serious side effects like kidney failure.

Trasylol, known generically as aprotinin, is marketed by Bayer AG. Trasylol was approved in 1993 and is used during heart bypass surgeries to prevent bleeding. Last year, a study published in the Journal of the American Medical Association found that Trasylol increased the risk of death by about 50 percent for some patients. A second 2006 Trasylol study, known as the I3 drug report, suggested that Trasylol increased the risk of a patient dying by 54 percent. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes.

Last December, the FDA updated the Trasylol label to include a black box warning – the agency’s strictest safety notice – stating that the drug placed patients at a high risk of kidney failure. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries. In September, an FDA advisory panel agreed with the assessment that Trasylol had a high risk of causing serious side-effects, and it recommended that Trasylol undergo further clinical testing.   But the FDA panel also voted that Trasylol should stay on the market.

The latest Trasylol troubles began last week, after it was learned that Canadian regulatory authorities had halted a clinical trial that was comparing the effectiveness of Trasylol with other similar drugs.   The Canadian Data Safety Monitoring Board had stopped the Trasylol trial after a data analysis indicated that 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. While the patients in this Trasylol clinical trial did experience less serious bleeding, there were more deaths due to hemorrhage in the Trasylol group.

Last week, the FDA issued new guidance on Trasylol based on the Canadian findings.   In issuing this latest warning, the FDA said that that doctors who are considering using Trasylol should be aware of the risks and benefits of the drug, as well as the accumulating data suggesting Trasylol increases the risk of death compared to other antifibrinolytic medications.

The FDA also announced that it would be conducting another review of Trasylol’s safety in light of the Canadian clinical trial. Depending on its findings, the FDA could decide to once again modify Trasylol’s label, or it could take other regulatory action to restrict its use.

Trasylol Clinical Trail Halted Due to Bleeding, Death Risk

Thu, 25 Oct 2007 00:00:00 -0700

A Trasylol clinical trial has been halted according to the Food & Drug Administration (FDA) because patients enrolled in the study who took Trasylol had a higher risk of death from bleeding. The FDA’s decision to end the Trasylol clinical trial is just the latest disturbing news about this defective drug, which has also been linked to kidney failure.

Trasylol, known generically as aprotinin, is marketed by Bayer AG. Trasylol was approved in 1993 and is used during heart bypass surgeries to prevent bleeding. The drug works by blocking enzymes that dissolve blood clots. Trasylol has been undergoing an FDA safety review since 2006 when studies linked the drug to serious side effects, including kidney failure, heart attacks and stroke. Last December, the FDA updated the Trasylol label to include a black box warning – the agency’s strictest safety notice – stating that the drug placed patients at a high risk of kidney failure. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries.

The Trasylol clinical trail that was ended had been comparing its effectiveness with similar drugs, known as antifibrinolytic drugs. According to an FDA notice, the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. While the patients in this Trasylol clinical trial did experience less serious bleeding, there were more deaths due to hemorrhage in the Trasylol group.

The FDA convened an advisory panel last month to look at the drug’s safety problems, after two other studies linked Trasylol to an increased risk of death. One of those studies, known as the I3 drug report, suggested that Trasylol increased the risk of a patient dying by 54 percent. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes. The I3 drug report was withheld from the FDA by Bayer prior to another September 2006 advisory panel meeting on Trasylol’s safety. Bayer claims that this was an oversight, as the company’s management was not informed of the report until after the safety review.

A second study published last year in the Journal of the American Medical Association also suggested that Trasylol increased the risk of death by about 50 percent for some patients. During that study’s five-year examination period, 223 deaths occurred among 1072 patients treated with Trasylol.

While the September advisory panel meeting ended with a recommendation that Trasylol be allowed to remain on the market, the panel also said that the drug merited further study. In issuing this latest warning, the FDA said that that doctors who are considering using Trasylol should be aware of the risks and benefits of the drug, as well as the accumulating data suggesting Trasylol increases the risk of death compared to other antifibrinolytic medications. The FDA said it would be reevaluating Trasylol’s safety record, and could consider making further labeling changes or taking other regulatory action.

Trasylol Should Remain on Market Says FDA Panel, Despite Risk of Kidney Failure and Death

Thu, 13 Sep 2007 00:00:00 -0700

Drug Safety reviewers say Trasylol should remain on the market, despite being linked to an increased risk death. Yesterday, a Food & Drug Administration (FDA) advisory panel voted 16-1 to recommend that the FDA allow continued sales of Trasylol, although the experts on the panel concluded that more studies of the drug’s safety were needed.

Trasylol, marketed by Bayer AG, is used during heart bypass surgeries to prevent bleeding. The drug works by blocking enzymes that dissolve blood clots. Trasylol has been undergoing an FDA safety review since 2006 when studies linked the drug to serious side effects, including kidney failure, heart attacks and stroke. Last December, the FDA updated the Trasylol label to include a black box warning – the agency’s strictest safety notice – stating that the drug placed patients at a high risk of kidney failure. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries.

The FDA decided to convene this latest advisory panel after two other studies linked Trasylol to an increased risk of death. One of those studies, known as the I3 drug report, suggested that Trasylol increased the risk of a patient dying by 54 percent. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes. A second study published last year in the Journal of the American Medical Association also suggested that the risk of death increased by about 50 percent for some patients. During that study’s five-year examination period, 223 deaths occurred among 1072 patients treated with Trasylol.

The I3 drug report was withheld from the FDA by Bayer prior to a September 2006 advisory panel meeting on Trasylol’s safety. Bayer claims that this was an oversight, as the company’s management was not informed of the report until after the safety review.

For its part, Bayer denies that the last two studies are evidence that Trasylol is linked to high death rates, although the company has conceded that the drug is associated with higher rates of kidney failure. The company also says that Trasylol significantly reduces the need for blood transfusions during bypass surgery. Trasylol has been under fire for the past several years, in part because of the studies suggesting it is dangerous, but also because several generic drugs, specifically Amicar and Cyklokapron, have been found to be a safer choice for bypass patients, and cost just a fraction of what Bayer charges for Trasylol.

While the advisory panel did recommend that Trasylol be allowed to remain on the market, it also found that the drug merits further study. The FDA is not obligated to follow the advice of advisory panels, although in most cases it does.

Trasylol Kidney, Death Risks to Be Investigated by FDA Advisory Panel

Tue, 11 Sep 2007 00:00:00 -0700

Trasylol, a drug used to prevent bleeding during heart bypass surgeries that has been linked to kidney failure, will face the scrutiny of a Food & Drug Administration (FDA) advisory panel for the second time since 2006. The FDA undertook its first review of Trasylol in September 2006 after two studies found that the drug doubled the risk of kidney failure for patients undergoing bypass surgery. Since that first review, two other studies have found that Trasylol could increase the risk of death.

On its website, the FDA said that the purpose advisory panel safety review scheduled for tomorrow is to “provide recommendations about the overall risk-benefit assessment for Trasylol”. The FDA said that the panel would be paying special attention to information not submitted during the 2006 Trasylol safety review. Shortly before last September’s meeting, Trasylol’s manufacturer, Bayer Pharmaceuticals, received one of the two studies linking the drug to an increased risk of death, but Bayer did not pass the information on to the advisory panel. Bayer claims that this was an oversight, as the company’s management was not informed of the report until after the safety review. The results from that study, known as the I3 drug report, suggested that Trasylol increased the risk of a patient dying by 54 percent. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes. A second study published last year in the Journal of the American Medical Association also suggested that the risk of death increased by about 50 percent for some patients. During that study’s five-year examination period, 223 deaths occurred among 1072 patients treated with Trasylol.

The first Trasylol safety review resulted in changes to the drug’s label. Last December, the FDA updated the Trasylol label to include a black box warning – the agency’s strictest safety notice – stating that the drug placed patients at a high risk of kidney failure. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were risk for significant blood loss during bypass surgeries. This time around, the FDA will ask the panel about strengths and weaknesses in the latest Trasylol studies. The last two studies were observational, and did not involve clinical trials.

For its part, Bayer denies that the last two studies are evidence that Trasylol is linked to high death rates, although the company has conceded that the drug is associated with higher rates of kidney failure. Trasylol has been under fire for the past several years, in part because of the studies suggesting it is dangerous, but also because several generic drugs, specifically Amicar and Cyklokapron, have been found to be a safer choice for bypass patients, and cost just a fraction of what Bayer charges for Trasylol.

Heart surgery drug linked to death risk

Wed, 07 Feb 2007 00:00:00 -0800

A drug widely used to prevent excessive bleeding during heart surgery appears to raise the risk of dying in the five years afterward by nearly 50 percent, an international study found.

The researchers said replacing the drug aprotinin, sold by Bayer AG under the brand name Trasylol with other, cheaper medications for a year would prevent 10,000 deaths worldwide over the next five years.

The findings were more bad news for Trasylol: The same scientists found the drug raised the risk of kidney failure, heart attacks and strokes in a study published last year. Most of the deaths in the new study were related to those problems.

Bayer said in a statement that the findings are unreliable because Trasylol tends to be used in more complex operations and the researchers' statistical analysis did not fully account for the complexity of the surgery cases.

Nevertheless, the drug company said it will "work with regulatory agencies and external experts in the field to further evaluate the findings."

The study, published in Wednesday's Journal of the American Medical Association, intensifies questions about how best to track the safety of drugs after they have gone on the market. The Food and Drug Administration approved aprotinin in 1993.

Last year's study and other research led the FDA to review Trasylol's safety and order stronger warning labels in December. But that action wasn't strong enough, said Dr. Dennis Mangano of the nonprofit Ischemia Research and Education Foundation, lead author of both studies.

The FDA is already reviewing aprotinin's safety. The new study is an important contribution to that review, which could result in additional warnings, said Dr. Dwaine Rieves, deputy director in the FDA's Division of Medical Imaging and Hematology Products.

The drug works by blocking enzymes that dissolve blood clots, and Mangano speculated that clotting problems caused the deaths.

Mangano advised patients to ask their doctors what drug, if any, they will be given to slow bleeding during heart surgery and about the risks. Past patients should find out if they have been given aprotinin so their doctors can watch for problems, he said.

"I believe that for the vast majority of coronary bypass patients the drug should not be used," Mangano said. But he said the drug should remain on the market because some very high-risk patients may benefit from it.

Dr. Brett Sheridan, a heart surgeon with the University of North Carolina Health Care System who was not involved in the study, said several years ago he quit giving aprotinin almost entirely because he had seen more kidney damage in patients who got the drug.

"It's not a perfect study, but the data are compelling enough that we have to use aprotinin judiciously," Sheridan said of the new research.

The study followed 3,876 patients who had heart bypass surgery at 62 medical centers in 16 nations. Researchers compared patients who received aprotinin to patients who got other drugs or no anti-bleeding drugs. Over five years, 20.8 percent of the aprotinin patients died, versus 12.7 percent of the patients who received no anti-bleeding drug.

When researchers adjusted for other factors, they found that patients who got Trasylol ran a 48 percent higher risk of dying in the five years afterward.

The other drugs, both cheaper generics, did not raise the risk of death significantly.

Cost varies depending on dosage and length of surgery, but a two-hour bypass surgery might require $792 in Trasylol, compared with $7 to $35 for one of the generics.

The study was not a randomized trial, meaning that it did not randomly assign patients to get aprotinin or not. In their analysis, the researchers took into account how sick patients were before surgery, but they acknowledged that some factors they did not account for may have contributed to the extra deaths.

Aprotinin joins the painkiller Vioxx, drug-coated stents and other drugs and devices where safety concerns arose after the products were on the market.

"We don't know enough about what happens with drugs and devices once they go into the public domain," said Dr. Bruce Ferguson of East Carolina University, who wrote an editorial accompanying the new study. Drug companies will have to help pay for a better system of post-market safety research because the government can't afford to do it alone, he said.

Similarly, Mangano said: "I would love to see something change as a result of this."

Last week, FDA officials announced plans to assess safety in the first 18 months a drug is on the market.

The earlier study prompted at least two lawsuits against Bayer, including one from 78-year-old Tennessee resident Ada Williams, who was given the drug during heart surgery in 2004.

"She has to live the rest of her life on dialysis three days a week to keep her alive," said her attorney.

Costly bypass medication may raise death risk later

Wed, 07 Feb 2007 00:00:00 -0800

An expensive drug given to coronary artery bypass surgery patients to prevent excessive bleeding is linked to an increased risk of dying as long as five years after the operation, researchers report Wednesday.

More than 4 million patients worldwide have received aprotinin, sold as Trasylol, since 1985, the scientists write in the Journal of the American Medical Association. The Food and Drug Administration approved Trasylol for use in coronary bypass surgery patients in 1993. Last year, it was used 246,000 times in the U.S., the researchers say.

Trasylol has been under scrutiny for at least a year and has raised anew concerns about monitoring the safety of drugs once they're on the market. The new study is a followup to one the authors published in January 2006 that linked Trasylol to serious kidney problems, heart attacks and strokes in patients undergoing coronary bypass surgery. Another study, posted online in January 2006 and published in March, also linked Trasylol to kidney trouble.

The studies spurred the FDA to convene an advisory panel, which in September voted unanimously that Trasylol should stay on the market. The next week, the FDA announced it had just learned of another study, by Trasylol maker Bayer, which the company had not mentioned at the advisory panel meeting. That study suggests that Trasylol might increase the risk of serious kidney damage, death, heart failure and strokes, the FDA said in December, when it announced updated labeling for the drug. The label now warns about kidney problems and says that Trasylol should be used only in coronary bypass surgery patients who are at an increased risk for excessive bleeding.

The new, multi-center international study compared the death rates of four groups of patients who had undergone bypass surgery: 1,072 given Trasylol, 834 given aminocaproic acid; 442 given tranexamic acid and 1,374 who didn't receive any medication to prevent excessive bleeding. Patients who got aprotinin were about 50% more likely to die in the five years after surgery than patients who received no drug. Neither of the other drugs was linked to a significantly higher risk of death than no treatment.

Trasylol costs $1,300 per use, compared with $44 for aminocaproic acid and $11 for tranexamic acid, says lead author Dennis Mangano, head of the Ischemia Research and Education Foundation in San Bruno, Calif. Before his first study came out in January 2006, says Mangano, about half of U.S. coronary bypass surgery patients received Trasylol. But, he says, use of the drug dropped 37.5% in the first half of 2006.

"I think that clinicians are going to pay attention, and I think the use of the drug will drop again," he says.

In a statement responding to the new study, Bayer said that doctors tend to give Trasylol to the sickest of patients, which could skew findings about the drug's safety. Based on its initial review, "Bayer believes that the results of this study should not serve as a basis for affecting the use of aprotinin."

Keyvan Karkouti, lead author of the other paper last year linking Trasylol to kidney problems, called Mangano's new report "a good paper, and it definitely raises more questions and concerns."

In Canada, says Karkouti, an anesthesiologist at the University of Toronto, only bypass patients at the highest risk of bleeding 5% of bypass patients at his hospital receive Trasylol. Trasylol has been shown to be more effective than no treatment in that group, Karkouti says, but trials comparing its generic competitors with a placebo in high-risk patients haven't been done, because no drug company stands to gain from such a study. He says a Canadian study that's randomizing 3,000 moderate- to high-risk patients to Trasylol or one of its two generic competitors is expected to provide more answers about the drugs' relative safety and effectiveness.

International study: Five-year death rate higher in heart surgery patients who are given aprotinin

Wed, 07 Feb 2007 00:00:00 -0800

Patients who are given a widely used drug to prevent excessive bleeding during heart surgery are at increased risk of dying within five years following their operations, medical researchers have found in the largest study of its kind.

Results from an international analysis that focused on a drug called aprotinin, sold under the brand name Trasylol, revealed the risk of death increased by nearly 50 percent in patients given the drug during bypass operations. The medication, made by Bayer AG, was federally approved in 1993.

"I think something radical needs to be done," Dr. Dennis Mangano of the nonprofit Ischemia Research and Education Foundation in San Bruno, Calif., said, calling for a change in how the FDA approves drugs.

As lead investigator of the international research, Mangano found 20.8 percent of patients given aprotinin died of complications, which he said, could be directly traced to the drug. In the control group, only 12.7 percent of patients died. More than 3,800 patients at 62 medical centers in 16 countries were involved in the study.

Aprotinin obstructs the activity of enzymes that dissolve blood clots and thus affects numerous biological pathways involved in clotting. Because it affects so many pathways, Mangano said, the effects of the drug do not diminish after surgery. Vessels throughout the body continue to be affected, including the complex labyrinth of vessels throughout the kidneys. Mangano discovered last year that kidney failure can be a consequence. In this study, he found that patients were vulnerable to heart failure, heart attacks and strokes.

"The thrombosis takes months to years to manifest in death," he said.

In a statement yesterday, Bayer lambasted Mangano's study, which is published in today's issue of the Journal of the American Medical Association. The pharmaceutical giant labeled data in both of Mangano's studies "unreliable." Bayer officials said they "will work with regulatory agencies and external experts in the field to further evaluate the findings."

Even though aprotinin is not a household name, it has been given to an estimated 4 million patients. Not long after its approval, reports of liver toxicity began surfacing, doctors say.

"This is a very important study," said Dr. Stephen Lahey, chief of cardiovascular surgery at Maimonides Medical Center in Brooklyn. He said that while at Harvard University a decade ago, he and colleagues abandoned use of aprotinin after noticing complications.

Issues involving aprotinin are "unbelievably politically charged," Lahey said, "because the company that makes it is a very, very big company and it has a lot of literature saying aprotinin is fine." He was not involved in the research.

Mangano said if surgeons globally used either of two cheaper and less potent medications for a year, 10,000 lives would be spared over five years.

Aprotinin, drug used in cardiac surgery, heightens death risk: study

Wed, 07 Feb 2007 00:00:00 -0800

Researchers have found that as drug used to staunch blood loss in patients undergoing cardiac surgery can raise the risk of death over the medium term. According to a new study published in the February 7 issue of the Journal of the American Medical Association, the drug, aprotinin, was used on more than four million people worldwide since 1985 mainly for heart surgery.

Scientists from the Ischemia Research and Education Foundation in San Bruno, California found that aprotinin is associated with a increased risk of death in the five years after the surgery.

Their observational study of 3,876 patients at 62 medical centers around the world showed aprotinin use "was associated with a doubling to tripling of the risk of perioperative renal (kidney) dysfunction and failure requiring dialysis in patients undergoing primary, repeat or complex coronary artery surgery," the scientists said in a summary of the study.

"We estimate that over the past year, aprotinin was prescribed worldwide to at least 200,000 cardiac surgery patients having a profile similar to patients in our study," they said.

"For such patients, our study found a five percent absolute increase in five-year mortality (one percent per year for five years) associated with aprotinin use."

"Use of aprotinin among patients undergoing (coronary artery bypass graft) surgery does not appear prudent because safer and less expensive alternatives (i.e., aminocaproic acid and tranexamic acid) are available," the authors conclude.

Bayers Heart-Surgery Drug Increases Risk of Death

Wed, 07 Feb 2007 00:00:00 -0800

Bayer’s controversial heart-surgery drug aprotinin, marketed as Trasylol, is under fire yet again thanks to a new study that found that the drug carries with it an increased risk of long-term mortality. Trasylol is a widely used drug intended to reduce bleeding during open-heart surgery. The study appears in the February 7 issue of the Journal of the American Medical Association.

Researchers, led by Dr. Dennis T. Mangano of the Ischemia Research and Education Foundation (IREF), concluded that “in addition to the previously reported acute renal and vascular safety concerns, aprotinin use is associated with an increased risk of long-term mortality following CABG [coronary artery bypass graft] surgery. Use of aprotinin among patients undergoing CABG surgery does not appear prudent because safer and less expensive alternatives (ie, aminocaproic acid and tranexamic acid) are available.”

The new observational study of 3876 patients from 62 medical centers was conducted between November 11, 1996, and December 7, 2006. Survival rates were assessed at 6 weeks, 6 months, and annually for 5 years after CABG surgery. The results were rather alarming: During the five-year examination period, 223 deaths occurred among 1072 aprotinin-treated patients, equal to 20.8 percent of the group. That death rate was nearly two-thirds greater than that of control patients (12.7 percent). After controlling for various patient factors, the results showed that Trasylol patients faced a 48 percent greater risk of death within a five-year period than those not using any medication.

Patients treated with aminocaproic acid had a death rate of 15.8 percent and those treated with tranexamic acid patients had a death rate of 14.7 percent, meaning either of these two alternative therapies carries with it a significantly lower mortality risk than aprotinin. Significantly, the authors noted that “serious safety concerns extend beyond the perioperative period” and that “their consequences likely continue over months to years following administration of aprotinin.”

The findings of this study may have serious clinical implications. As the researchers wrote, “We estimate that over the past year, aprotinin was prescribed worldwide to at least 200,000 cardiac surgery patients having a profile similar to patients in our study. For such patients, our study found a 5 percent absolute increase in 5-year mortality (1 percent per year for 5 years) associated with aprotinin use, compared with either aminocaproic or tranexamic acid use. Thus, in 2006 alone, had aprotinin been replaced with either of these generic agents, we estimate that approximately 2,000 deaths per year for the next 5 years (or 10,000 total deaths) might have been avoided.”

In an editorial accompanying the report, Dr. T. Bruce Ferguson Jr. wrote, “This past year has been a complicated one for aprotinin, an antifibrinolytic serine protease inhibitor used to lessen bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Thirteen years after the initial approval of aprotinin by the U.S. Food and Drug Administration, the report by Mangano and colleagues … will intensify the debate about the benefits and risks associated with use of this drug. Perhaps more important, this aprotinin story illuminates the larger issue of postmarket safety evaluation surrounding drugs and devices in the current medical environment.”

Bayer has suffered a number of setbacks related to Trasylol in recent months. An IREF study published early last year reported an increase in the possibility of kidney failure, heart attack, and stroke in Trasylol patients compared to those treated with other drugs. A second study also noted an increased risk of kidney damage.

In addition, on September 27, 2006, a week after the FDA held a public meeting of the Cardiovascular and Renal Drugs Advisory Committee to discuss the safety and risk-benefit profile for Trasylol, Bayer admitted to having conducted an additional internal study, which found that, in addition to severe kidney damage, Trasylol may increase the chance for death, congestive heart failure, and strokes. A few weeks ago, the company decided to halt three clinical trials that were intended to expand the approved usage of the drug, which currently is only approved for use in the course of coronary artery bypass graft surgery.

Bayer said the findings of this most recent study were “not reliable,” citing “major differences in clinical practice among the contributing countries” and questioning the authors’ “methodological and analytical approaches.”

FDA strengthens safety warning on aprotinin label

Mon, 18 Dec 2006 00:00:00 -0800

The FDA has strengthened the label safety warning for the antifibrinolytic drug aprotinin (Trasylol, Bayer), emphasizing the importance of limiting use of the agent to patients undergoing CABG.

The labeling change comes after months of FDA review, culminating in a Cardiovascular and Renal Drugs Advisory Committee hearing in late September 2006. The committee's conclusions—that the drug is a safe and effective way to reduce bleeding complications in high-risk CABG—have been eclipsed in recent months by ongoing debate over new data pointing to increased risk of death, serious kidney damage, congestive heart failure, and stroke with the drug, as reported by heartwire.

In an FDA press release issued last Friday, Dr Steven Galson, director of the agency's Center for Drug Evaluation and Research, explained, "The purpose of the label change is to inform physicians and patients about the risks associated with Trasylol and to ensure they understand the new warnings and use the product as directed by the label."

The new labeling emphasizes that aprotinin should be used only in patients undergoing CABG with cardiopulmonary bypass, who are at an increased risk for blood loss and blood transfusion. The new label also warns that aprotinin increases the risk of kidney damage and provides suggestions for managing and reducing risk of hypersensitivity reactions.

Commenting on the labeling changes for heartwire, Dr William Hiatt (University of Colorado Health Sciences Center, Denver), who chaired the committee hearing in September, said it was appropriate for the FDA to focus on renal risks. "In our Cardio Renal review, the strongest safety signal in the data we had before us was the renal damage, and it appears that the FDA is keying on that, which is appropriate."

Hiatt continued, "I strongly agree that physicians need to stick to the labeled indications for Trasylol, given the potential for safety concerns. The FDA is also emphasizing the need to stay on label, which is appropriate."

Hiatt also reminded heartwire that at the time the FDA panel met to review aprotinin, one safety study—by Mangano et al—had not been independently reviewed by the FDA and that a second analysis commissioned by the drug manufacturer did not come to light until after the committee hearing. Ongoing review of that information may necessitate further action. Accordingly, said Hiatt, "The most important phrase [in the FDA's announcement of the labeling changes] is the second-to-last sentence, that the review is 'continuing and may result in other actions.' I support that approach, too."

FDA Approves New Warning for Bayer Drug

Fri, 15 Dec 2006 00:00:00 -0800

Government health officials said Friday they have approved a new label for Bayer's Trasylol that highlights the possible risk of kidney damage associated with taking the drug.

More than 600,000 people worldwide were treated with the drug in 2005, according to Bayer, which collected $291 million in sales from Trasylol. Annual revenue for the company was $34.7 billion in 2005.

Trasylol is the only drug approved by the FDA to reduce blood loss during coronary artery bypass surgery. The new label states that the drug should only be used on patients who are at an increased risk for blood loss and blood transfusion during the surgical procedure.

FDA began reassessing the safety of the drug earlier this year, when two separate studies suggested the drug was linked to heart attack, stroke and kidney problems. In September, Bayer submitted new data to the FDA about risks of Trasylol, days after a public hearing was held to review the drug's labeling. The company said it should have disclosed the results earlier and suspended two senior staff members as a result of the incident.

A Bayer spokesman said the company is still investigating why the results were witheld.

Bayer Suspends 2 Over Trasylol Data

Fri, 13 Oct 2006 00:00:00 -0700

Bayer AG said Friday it suspended two employees involved in the decision to withhold data from federal health officials showing the company's drug Trasylol can cause deadly side effects.

Bayer, headquartered in Germany, is investigating why a study showing that Trasylol can increase the risk of death, kidney damage, heart failure and stroke was not disclosed at a Sept. 21 meeting with the Food and Drug Administration to assess the safety of the drug. The company did not make the study public until more than a week after the meeting.

Trasylol is the only FDA-approved drug used to reduce blood loss during coronary artery bypass surgery.

Based on preliminary investigations the company believes the decision "was a serious error in judgment by two individuals." The drug maker also said it retained Fred Fielding of the law firm Wiley Rein & Fielding to conduct an independent investigation of the decision to withhold the data.

The FDA has been reassessing the safety of Trasylol since February, when two separate studies suggested the drug was linked to heart attack, stroke and kidney problems.

More than 600,000 patients worldwide were treated with the drug in 2005, according to Bayer. The company sold $291 million worth of Trasylol last year. Bayer's annual revenue was $34.7 billion in 2005.

FDA Statement Regarding New Trasylol Data

Fri, 29 Sep 2006 00:00:00 -0700

Since January, 2006, the Food and Drug Administration (FDA) has been conducting a safety review of Trasylol (aprotinin injection). The review was triggered by the results of two published research studies: one that reported an increase in the chance of kidney failure, heart attack and stroke in patients treated with Trasylol compared to those treated with other similar drugs, and the other that reported an increase in kidney dysfunction compared to another drug. On September 21, 2006, FDA held a public meeting of the Cardiovascular and Renal Drugs Advisory Committee to discuss the safety and overall risk-benefit profile for Trasylol. At that meeting, the committee discussed the findings from the two published observational studies, the Bayer worldwide safety review, and the FDA review of its own post-marketing database.

On September 27, 2006, Bayer Pharmaceuticals told FDA that it had conducted an additional safety study of Trasylol. The preliminary findings from this new observational study of patients from a hospital database reported that use of Trasylol may increase the chance for death, serious kidney damage, congestive heart failure and strokes. FDA was not aware of these new data when it held the September 21, 2006, Advisory Committee meeting on Trasylol safety. FDA is actively evaluating these new data and their implications for appropriate use of the drug.

While FDA conducts its evaluation of this new safety study, we recommend the following to healthcare providers:

Physicians who use Trasylol should carefully monitor patients for the occurrence of toxicity, particularly to the kidneys, heart, or brain, and promptly report observed adverse event information to Bayer Pharmaceuticals, the drug manufacturer, or to the FDA MedWatch program, by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), or by the Internet at http://www.fda.gov/medwatch/index.html.
Physicians should consider limiting Trasylol use to those situations where the clinical benefit of reduced blood loss is essential to medical management of the patient and outweighs the potential risks.

These recommendations are similar to those provided in a February 8, 2006, FDA Public Health Advisory and information sheets for health care professionals and patients which were based on the published studies mentioned above. See http://www.fda.gov/cder/drug/infopage/aprotinin/default.htm.

Trasylol works to slow or prevent bleeding, and is used to reduce blood loss and the need for blood transfusion during some types of heart surgeries. Trasylol is made from the lung tissue of cattle.

In the published studies and the recently supplied Bayer study, patients were not assigned at random to receive various treatments, but rather had their treatment chosen by their physician as part of their standard medical care. Consequently, in these safety studies, patients receiving Trasylol may have had a higher chance for serious complications to begin with as compared to patients receiving no treatment or treatment with another drug intended to decrease bleeding. This possibility complicates the assessment of whether the available studies show that Trasylol treatment, rather than other factors, increased the chance for serious kidney or heart complications.

The new study was done for Bayer by a contract research organization. Existing hospital data from 67,000 records of patients undergoing coronary artery bypass graft surgery were examined. 30,000 of the patients were treated with Trayslol and 37,000 were treated with alternate products. Using complex epidemiological and statistical methods, the report suggested that patients receiving Trasylol were at increased risk for death, kidney failure, congestive heart failure and stroke.

Healthcare providers and patients are encouraged to report adverse event information to FDA via the MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), or by the Internet at http://www.fda.gov/medwatch/index.html.

FDA Urges Limited Use of Trasylol Pending Review of Data Showing Increased Risks of Heart Attack, Stroke, and Kidney Failure

Thu, 09 Feb 2006 00:00:00 -0800

The Food and Drug Administration (FDA) has issued an advisory to doctors urging them to limit the use of Bayer AG’s heart-surgery medication, Trasylol, pending an agency review of research that shows the drug causes increased risks serious medical problems including stroke, heart attack, and kidney failure.

Trasylol is widely used to prevent blood loss in patients during artery bypass graft surgery (CABG).

In a statement from the FDA, Dr. Steven Galson, Director of the agency’s Center for Drug Evaluation and Research, said: "We're working to evaluate the potential risks and determine whether there is a need for further action. In the meantime, we advise providers to carefully assess the benefits and risks of the drug for their patients."

While this evaluation is conducted by the FDA, doctors are being urged to limit the use of Trasylol to those cases where the benefit of reducing blood loss during surgery outweighed the potential risks that are now being studied.

The FDA plans to hold an advisory committee meeting later this year to reassess the risk-benefit analysis in light of existing data and to determine whether additional safety measures are required.

Only last month, a report in the New England Journal of Medicine claimed that Trasylol doubled the risk of stroke and kidney failure and increased the chance of heart attack or heart failure by 55%. Bayer said the results were "not consistent with the more than 15 years of clinical data and experience Bayer has amassed on this drug."

Bayer intends to cooperate with the FDA and other regulators while it too analyzes the data. The company also plans to issue an information letter in the next few days to heart surgeons, anesthetists and hospital pharmacists about the drug.

FDA Issues Public Health Advisory for Trasylol

Wed, 08 Feb 2006 00:00:00 -0800

The Food and Drug Administration today issued a Public Health Advisory alerting doctors who perform heart bypass surgery, and their patients, that Trasyolol (aprotinin injection), a drug used to prevent blood loss during surgery, has been linked in two scientific publications to higher risks of serious side effects including kidney problems, heart attacks and strokes in patients who undergo artery bypass graft surgery.

"FDA is conducting a thorough evaluation of the safety profile for this drug in light of the recent publications," said Dr. Steven Galson, Director of FDA's Center for Drug Evaluation and Research. "We're working to evaluate the potential risks and determine whether there is a need for further action. In the meantime, we advise providers to carefully assess the benefits and risks of the drug for their patients."

FDA advises health care providers to be aware of the following:

·    Physicians who use Trasylol should carefully monitor patients for the occurrence of toxicity, particularly to the kidneys, heart or central nervous system and promptly report adverse event information to Bayer, the drug manufacturer, or through the FDA Medwatch program.
·    Physicians should consider limiting Trasylol use to those situations in which the clinical benefit of reduced blood loss is essential to medical management of the patient and outweighs the potential risks.
·    FDA is working with the manufacturer to examine the safety and benefits of Trasylol in light of the recent data and the evolving practice of medicine.
·    Patients should discuss all major risks for heart bypass surgery with their healthcare providers. These include the risks for bleeding and the available ways to lessen the risk for bleeding.

Trasylol (aprotinin injection) is the only product approved by FDA for the prevention of peri-operative blood loss and the need for blood transfusion among patients undergoing coronary artery bypass graft surgery. The drug aids the body's ability to stop bleeding and is used to lessen the bleeding risk during this surgical procedure. This surgery is done to bypass clogged arteries.
.
FDA is evaluating the studies more closely, along with other scientific literature and reports submitted to the FDA through the MedWatch program, to determine if labeling changes or other actions are warranted. One study, published in the New England Journal of Medicine, reported that patients who received Trasylol had higher rates of serious kidney problems, heart attacks, and stroke compared to treatment with other drugs to prevent bleeding or to no treatment; the second study, reported in Transfusion, reported more cases of decreased kidney function in patients treated with Trasylol compared to another treatment to prevent bleeding. A limitation of both studies was that doctors chose which patients were to receive Trasylol or another treatment. It is possible that patients treated with Trasylol may have been sicker than other patients. The studies used complex statistical methods to adjust for possible differences in patient risk factors.

The agency also anticipates convening an advisory committee meeting in 2006 to discuss the existing data about the risks and benefits of Trasylol, and if additional safety measures need to be taken. The FDA will notify health care providers and patients in a timely manner following further scientific investigation of adverse event reports.

FDA also urges health care providers and patients to report adverse event information to FDA via the MedWatch program by phone (1800-FDA-1088), by fax (1-800-FDA-1078) or internet.

The Public Health Advisory is available on line at http://www.fda.gov/cder/drug/advisory/aprotinin.htm.

For more information please visit http://www.fda.gov/cder/drug/infopage/aprotinin/default.htm

FDA Public Health Advisory Aprotinin Injection (marketed as Trasylol)

Wed, 08 Feb 2006 00:00:00 -0800

On January 26, 2006, The New England Journal of Medicine (NEJM) published an article by Mangano et al. reporting an association of Trasylol (aprotinin injection) with serious renal toxicity and ischemic events (myocardial infarction and stroke) in patients undergoing coronary artery bypass grafting surgery (CABG). Another publication (Transfusion, on-line edition, January 20, 2006, Karkouti, et al.) suggests an association between aprotinin administration and renal toxicity among patients undergoing cardiac surgery with cardiopulmonary bypass.

FDA is evaluating these studies, along with other studies in the literature and reports submitted to the FDA through the MedWatch program, to determine if labeling changes or other actions are warranted.

While FDA is continuing its evaluation, we are providing the following recommendations to healthcare providers and patients:

    * Physicians who use Trasylol should carefully monitor patients for the occurrence of toxicity, particularly to the kidneys, heart, or central nervous system and promptly report adverse event information to Bayer, the drug manufacturer, or to the FDA MedWatch program, as described at the end of this advisory.
    * Physicians should consider limiting Trasylol use to those situations where the clinical benefit of reduced blood loss is essential to medical management of the patient and outweighs the potential risks.

The study reported in the NEJM was an observational study of patients undergoing CABG who received either Trasylol, one of two other drugs intended to decrease peri-operative bleeding (aminocaproic acid or tranexamic acid), or no specific drug treatment.

A limitation of the study was that patients were not assigned at random to receive the treatments, but rather had their treatment chosen by their physician as part of their standard medical care.   Consequently, patients receiving Trasylol may have been at higher risk to begin with for these serious adverse events compared to patients receiving no treatment or treatment with another drug intended to decrease bleeding. This possibility prevents a direct assessment of whether Trasylol altered the risk for serious adverse events. The study investigators used statistical procedures (multivariable logistic regression and propensity-score adjustment) to try to adjust for known differences between the treatment groups. Using these procedures, their study concluded that Trasylol was associated with more adverse outcomes. Other findings in the study suggested that patients receiving higher Trasylol dosages were at greater risk than those receiving lower dosages.

The study reported in the on-line edition of Transfusion was also an observational study that used statistical methodology to compare outcomes from patients undergoing CABG. The patients in this study received, at physician direction, either Trasylol or another drug intended to decrease the risk for perioperative bleeding. This study suggested that Trasylol administration increased the risk for renal dysfunction. This study has some of the same limitations as the NEJM publication.

In pre-marketing clinical studies conducted among approximately 3,000 patients undergoing CABG, the risks and benefits of Trasylol were determined in clinical studies that randomized patients to either a placebo or Trasylol. In these studies, the risks for serious renal toxicity and cardiovascular events were determined to be similar between patients receiving Trasylol and those receiving placebo. However, in one study assessing coronary graft patency, Trasylol administration was associated with an increased risk of graft closure. The FDA will work with the authors of the publications and the manufacturer of Trasylol to carefully evaluate the risks and benefits associated with use of Trasylol in CABG. The FDA anticipates the public presentation of the recently reported information and other data at an advisory committee in the near future. The FDA will notify health care providers and patients in a timely fashion as new information becomes available.

Parker & Waichman, LLP Evaluating Trasylol Claims After Study Links Medication to Kidney Failure, Stroke and Heart Attack -- BAY

Tue, 31 Jan 2006 00:00:00 -0800

Parker & Waichman, LLP (www.yourlawyer.com) announces that, in addition to numerous inquiries from potential clients, it has been retained in a case involving the use of Trasylol and is actively evaluating claims concerning Trasylol, a drug commonly used during heart surgery to reduce blood loss. Trasylol, known generically as Aprotinin, is manufactured by Bayer AG (NYSE:BAY) and is estimated to have generated $600 million in sales in 2005.

A study reported last week in the New England Journal of Medicine shows that Trasylol is linked to serious side effects. The study of 4,374 patients demonstrated that Trasylol at least doubles the risk of kidney failure and stroke, or encephalopathy, and raises the risk of heart failure or heart attack by 55 percent. Parker & Waichman, LLP represents victims of Trasylol and is actively evaluating claims on their behalf. For more information about Trasylol and the study published in the New England Journal of Medicine, please visit www.yourlawyer.com/topics/overview/trasylol or www.trasylol-lawsuit.com.

Trasylol was initially approved by the FDA in 1993 and is indicated to reduce perioperative blood loss and the need for blood transfusion in patients undergoing cardiopulmonary bypass (CPB) in the course of coronary artery bypass graft surgery (CABG). While Trasylol is only approved for specific heart surgeries, it is commonly used for other surgeries including orthopedic procedures. Prior to the publication of the study reported in the New England Journal of Medicine, Bayer AG filed a request with the FDA seeking Trasylol approval for hip and spinal surgeries.

Trasylol, which is derived from the lungs of bovine, is significantly more dangerous than similar drugs used to reduce blood loss. The two generic drugs examined in the New England Journal of Medicine study, aminocaproic acid and tranexamic acid, were found to be significantly safer and just as effective as Trasylol. Furthermore, these generics are significantly less expensive than Trasylol; Trasylol costs more than $1,000 per patient versus $10 to $50 per patient for the generic drugs. The researchers estimated that using one of these generic drugs instead of Trasylol could prevent as many as 11,050 dialysis complications worldwide, and reduce drug costs by $250 million per year.

"This has all the signs of a drug that should not be on the market. It's more dangerous than the alternatives, which are just as effective. It's also more costly to patients and the healthcare system as a whole. There is no reason for this drug to be on the market today," said Jason Mark, an attorney with Parker & Waichman, LLP.

Most surgical patients are unaware of the medications they are given during the course of a surgical procedure. Trasylol is used during surgery, and it is therefore unlikely that patients would be aware that this drug was administered. For this reason, Parker & Waichman, LLP is encouraging all patients who suffered kidney failure, heart attack, heart failure or stroke after any surgical procedure to request a free case evaluation at www.yourlawyer.com/topics/overview/trasylol.

About Parker & Waichman, LLP

Parker & Waichman, LLP is a leading products liability and personal injury law firm that represents plaintiffs nationwide, with offices in New York and New Jersey. Parker & Waichman, LLP has assisted thousands of clients in receiving fair compensation for injuries resulting from defective medications and medical devices. For more information on Parker & Waichman, LLP please visit: www.yourlawyer.com, or call 1-800-LAW-INFO (1-800-529-4636).

CONTACT: Parker & Waichman, LLP
         Jason Mark, Esq.
         (800) LAW-INFO OR (800)529-4636
         jmark@yourlawyer.com
         www.yourlawyer.com

Heart-surgery drug risky, researchers find

Thu, 26 Jan 2006 00:00:00 -0800

A drug widely used during heart surgery to control bleeding doubles the risk of kidney damage, forcing an estimated 10,000 patients onto dialysis each year, according to a new study from a group that is calling for surgeons to abandon its use.

Known as aprotinin, the drug also increases the risk of heart attack 48 percent, heart failure 109 percent and stroke 181 percent, according to a study among nearly 4,400 patients reported today in the New England Journal of Medicine.

The researchers said the drug is not even needed in most cases because there are two generic drugs that cost a tenth as much and are nearly as good at stopping bleeding without increasing risks.

``I wonder how we can ethically prescribe aprotinin when there are alternatives that are safer,'' said Dr. Dennis Mangano of the Ischemia Research and Education Foundation, who led the study.

The drug, which is derived from the lung tissue of cows, was approved by the Food and Drug Administration in 1993. It is used in a significant number of the 1 million heart surgeries performed worldwide each year.

An FDA official said the agency is aware of the study and is reviewing the data.

Bayer, which manufactures the drug and sells it under the brand name Trasylol, said in a statement that it had not yet analyzed the study, but that the results were not consistent with its own experience.

Study: Cardiac Drug Doubles Risk of Kidney Failure

Thu, 26 Jan 2006 00:00:00 -0800

Aprotinin. a drug approved by the FDA, marketed internationally for the last 13 years, and given to an estimated one million surgery patients to limit bleeding has now been proven to double a patient's risk of kidney failure, and increase the risk of heart attack, heart failure, and stroke.

The results, published in this week's New England Journal of Medicine, are based on an independent, non-commercial, observational study conducted by The Ischemia Research and Education Foundation (IREF).

"Our study provides compelling evidence of aprotinin's serious risks, and strongly suggests discontinuation of use and replacement with either of the two alternative generic and far less costly medications proven safe in this study," said IREF founder and principal scientist, Dennis T. Mangano, Ph.D., M.D.

"Certainly, our findings coming on the heels of the Vioxx experience indicate that the problem of drug safety is not only ubiquitous, but also much more elusive than previously thought."

In fact, Mangano said, the findings raise even more troubling concerns, for:

(1) aprotinin has been on the market for three times as long as Vioxx, yet few comprehensive safety studies have been conducted since approval;

(2) the life-threatening complications with aprotinin occurred far more frequently than those with Vioxx; and

(3) far less expensive generic alternatives to aprotinin which are equally effective in limiting bleeding have been available, but have been underused.

The article states that replacing aprotinin with one of two safe generic drugs would annually prevent as many as 11,050 dialysis complications, save at least $1 billion in healthcare (dialysis) costs, and reduce drug costs by at least $250 million.

Each year approximately one million patients worldwide undergo surgical treatment following a heart attack, with the majority of these patients receiving one of three antifibrinolytic agents to limit blood loss during surgery: aprotinin (Bayer Healthcare Pharmaceuticals, Inc.), aminocaproic acid (generic), or tranexamic acid (generic).

The two generic drugs have proven safe in limiting blood loss, and do not have the harmful effects of aprotinin. Patients scheduled for cardiac surgery should consult their physicians and avoid this risk, Mangano said.

Aprotinin was approved by the U.S. Food and Drug Administration in 1993 and is manufactured by Bayer under the brand name Trasylol. Over the past three years, Trasylol sales have accelerated, with 2006 sales projected in excess of $600 million.

"We estimate that as many as 10,000 patients may be unnecessarily on dialysis today due to aprotinin use. This serious impact on human lives underscores once again the necessity for meticulous, post approval surveillance, as well as ongoing, unbiased analysis of drug safety all conducted by entirely independent entities," said Mangano.

"This is easier said than done, however, for the economic forces are and will continue to be substantial, with little corporate incentive to identify safety problems once drugs are approved and marketed."

The New England Journal of Medicine article documents how aprotinin use was associated with a two-fold increase in renal failure requiring dialysis in patients undergoing both complex coronary artery surgery and primary surgery, excluding prior cardiac and current valve surgery.

Among primary surgery patients, Dr. Mangano and colleagues found that aprotinin use also increased risk of myocardial infarction (48 percent), heart failure (109 percent), and stroke (181 percent).

Neither of aprotinin's generic competitors, aminocaproic acid and tranexamic acid, was associated with increased renal, cardiac or cerebral events.

Aprotinin is at least ten times more expensive than its generic competitors.

Multiple Risks of Surgery Drug Seen

Thu, 26 Jan 2006 00:00:00 -0800

A drug widely used during heart surgery to control bleeding doubles the risk of kidney damage, forcing an estimated 10,000 patients onto dialysis each year, according to a study from a group calling for surgeons to abandon its use.

Known as aprotinin, the drug also increases the risk of heart attack by 48%, heart failure by 109% and stroke by 181%, the study of about 4,400 patients reports today in the New England Journal of Medicine.

The researchers added that the drug was not even needed in most cases because there were two generic drugs that cost a tenth as much and were nearly as good at stopping bleeding yet produced no increased risk.

"I wonder how we can ethically prescribe aprotinin when there are alternatives that are safer," said Dr. Dennis T. Mangano of the Ischemia Research and Education Foundation, who led the study.

The drug, which is derived from the lung tissue of cows, was approved by the Food and Drug Administration in 1993. It is used in a significant number of the 1 million heart surgeries performed worldwide each year, largely because it is slightly more effective than alternative drugs and has been well-marketed by its manufacturer, Bayer Corp.

Surgeons and anesthesiologists had suspected potential problems with the drug for many years, but the number of adverse side effects was lost among the huge number of patients given the drug.

"We didn't have good, hard data to prove it," said Dr. O. Wayne Isom, chairman of the department of cardiac and thoracic surgery at New York Presbyterian Hospital/Weil Cornell Medical College.

The results are "pretty much undebatable," Isom said.

The study estimated that the side effects from aprotinin had increased medical costs by more than $1 billion per year worldwide.

A spokesman for the FDA said the agency was aware of the study and was reviewing the data.

Bayer, which sells aprotinin under the brand name Trasylol, said in a statement that it had not analyzed the study but the results were not consistent with its experience.

Bayer, with annual sales of about $40 billion, has predicted about $606 million in sales of the drug this year, nearly triple the $213 million of 2004.

The study was conducted by a consortium of surgeons called the Multicenter Study of Perioperative Ischemia Research Group, sponsored by the Ischemia Research and Education Foundation in San Bruno, Calif. The groups receive no money from pharmaceutical companies.

In other recent studies, the consortium has shown that giving inexpensive beta blockers after major surgery could save 250,000 lives a year, that aspirin use after heart surgery reduces the risk of blood clots, and that the painkiller Bextra is associated with stroke and the impaired healing of wounds.

Mangano said the team started the study because the medical and surgical treatments of heart attacks were contradictory.

Medical treatment uses clot-dissolving agents and a class of drugs that inhibit clotting, called antifibrinolytics, to forestall further attacks.

But in heart surgery, drugs such as aprotinin are used to promote clot formation to prevent internal bleeding.

"But isn't the patient who received aprotinin likely" to have a heart-attack-inducing clot? Mangano asked. "It seems very logical."

The team enrolled 4,374 patients at 69 medical centers in seven countries who were undergoing coronary surgery to reopen a blocked artery.

The control group, which totaled 1,374 patients, received a placebo, while 1,295 received aprotinin, 883 were given epsilon-aminocaproic acid and 822 received tranexamic acid.

Epsilon-aminocaproic acid and tranexamic acid are generic drugs that promote clot formation. A dose of the former costs $11 and a dose of the latter $44; a dose of Trasylol costs $1,300.

The most common side effect in the study was kidney dysfunction or failure, occurring in 8% of those receiving aprotinin and in 4% of those receiving tranexamic acid and 3% of those receiving epsilon-aminocaproic acid or a placebo.

The result is not surprising, Mangano said, because other studies have shown that aprotinin is taken up by tubules in the kidneys and stays there for 24 hours or longer, interfering with normal organ functions.

The side effects were not seen in earlier studies, he said, because they were too limited to illuminate the relatively small difference in incidence between the two groups of patients. The other serious side effects caused by the drug involved even fewer patients.

"If this data is correct, it will change our practices," said Dr. Nicola D'Attellis, a cardiac anesthesiologist at Cedars-Sinai Medical Center in Los Angeles. "This is really going to push people to do other research."

The study also showed that the risk of serious side effects increased with larger doses.

That is significant, Dr. Gus J. Vlahakes of the Harvard Medical School wrote in one of two editorials in the New England Journal of Medicine, because Bayer is initiating trials using aprotinin to reduce inflammation after cardiac surgery. The trials involve higher doses than are now used.

"Now the onus is on [Bayer] to prove that, for any other application, the drug is safe," Mangano said.

Clotting drug increases kidney risk, study finds

Thu, 26 Jan 2006 00:00:00 -0800

A drug commonly used to prevent excessive bleeding in heart-surgery patients greatly increased the risk of kidney failure, a new international study found.

The drug aprotinin marketed under the brand name Trasylol is the second clotting medication in two weeks linked to serious complications.

Heart-bypass patients who were injected with Trasylol during surgery had double the risk of kidney failure and an increased risk of heart problems compared with those who got other drugs, researchers reported in today's New England Journal of Medicine.

"Our findings raise serious concerns regarding the safety of an approved drug intended to limit blood loss in at-risk patients undergoing surgery," wrote Dr. Dennis Mangano of the Ischemia Research and Education Foundation, which led the study.

The San Bruno, Calif.-based foundation is a nonprofit organization founded in 1987 that funds cardiovascular research.

The Food and Drug Administration approved Trasylol in 1993 to control bleeding in patients undergoing open-heart surgery and minimize the need for blood transfusions. The drug works by blocking enzymes that dissolve blood clots.

Trasylol's maker, Germany-based Bayer AG, insists the drug is safe based on its own experiments but said it alerted regulatory authorities in the United States, Canada, Australia and Europe about the latest research.

Trasylol is the latest clotting drug to spark safety concerns. Last week, other researchers reported that the hemophilia drug Novoseven was linked to deaths, heart attacks and strokes in patients who took the drug to treat other types of excessive bleeding, such as cerebral hemorrhages.

Global sales for Trasylol reached $210 million in 2005, according to Bayer. Last month, chief executive Werner Wenning put the sales potential for the drug at more than $600 million.

Trasylol Kidney Failure Lawyer Injury Attorney Recall

Thu, 26 Jan 2006 00:00:00 -0800

DOWNLOAD OUR Trasylol INFORMATION PACKAGE

Trasylol Injury Lawyers / Attorneys

Keywords: Trasylol Kidney Failure Lawyer Injury Attorney Recall

The Trasylol injury lawyers at our firm are currently investigating instances where heart surgery patients died after being treated with Trasylol. Since the Bayer AG drug was brought to market in 1993, it has been used in a third of all open heart surgeries in the US. However, numerous studies have indicated that Trasylol puts such patients at a higher risk of death. In November 2007, Trasylol was finally removed from the market after a portion of a Canadian clinical trial was halted because Trasylol subjects were dying at a higher rate than others in the study. Our Trasylol injury lawyers have concluded that Bayer attempted to cover up Trasylol's deadly side effects, allowing many patients to die needlessly. The Trasylol injury lawyers at our firm will work hard to help the families of Trasylol victims receive the compensation they deserve for their tragic losses.

In November 2007, the Canadian Data Safety Monitoring Board had stopped a Trasylol trial - known as the BART clinical study - after a data analysis indicated that the 30-day mortality risk in the study’s Trasylol patients was nearing “statistical significance”. Following the revelations over the Canadian Trasylol study, Bayer suspended sales of the drug in the US, Canada and Germany. The Trasylol injury lawyers at our firm believe that this dangerous drug should have been removed from the market long ago, and it our intention to hold Bayer accountable for the deaths caused by Trasylol.

FDA, Bayer Slow to Act on Trasylol Death Reports

In September 2006, Dr. Dennis Mangano presented a study he authored to the Food & Drug Administration (FDA) which found that Trasylol increased the risk of kidney failure requiring dialysis. Hs study, published in the Journal of the American Medical Association, also found that Trasylol increased the risk of death by about 50 percent for some patients. Bayer executives attended Mangano’s presentation in order to defend Trasylol, and the defective drug was allowed to remain on the market.

What the Bayer executives did not tell the FDA was that their own Trasylol study, known as the I3 drug report, confirmed Mangano’s findings. That study, which analyzed a database of hospital patients treated with the drug, suggested that Trasylol could also increase the likelihood of serious kidney damage, congestive heart failure and strokes. Bayer claims that this omission was an oversight, as the company’s management was not informed of the report until after the safety review. The Bayer study looked at more than 78,000 patients nationwide in a period from January 1, 2003 to March 31, 2006. After adjusting for other factors, the researchers found the risk of death after surgery was 64 percent higher in the Trasylol group than in those taking a comparison drug.

Following the September 2006 meeting, the FDA updated the Trasylol label to include a black box warning - the agency’s strictest safety notice - stating that the drug placed patients at a high risk of kidney failure and death. The black box warning also cautioned that the use of Trasylol should be reserved only for patients who were at risk for significant blood loss during bypass surgeries.

Another FDA advisory panel that met in September 2007 agreed with the assessment that Trasylol had a high risk of causing serious side-effects, and it recommended that Trasylol undergo further clinical testing. However, the FDA panel also voted that Trasylol should stay on the market. However, in November - just a few months after decision -- the FDA asked Bayer to suspend Trasylol sales after learning of the Canadian study had been halted.

Even after Trasylol sales were halted, other studies continued to show that the drug put patients at a needlessly high risk of death. A Trasylol study released in February 2008 looked at more than 10,000 patients who had bypass surgeries at Duke University Medical Center from 1996 through 2005. It found that 6.4 percent of patients who were given Trasylol died within 30 days of the surgery, a rate nearly 2½ times higher than patients who got another drug or who received no treatment for excessive bleeding. At one year after surgery, almost 16 percent of Trasylol patients had died — again, roughly 2½ times higher than the other two patient groups.

The Trasylol injury lawyers at our firm believe that the vast majority of the deaths were avoidable. Dr. Mangano, the author of the 2006 Trasylol study ignored by the FDA, agrees. In February 2008, Dr. Mangano told “60 Minutes” the he believes Trasylol should have been taken off the market when he published his study in 2006. Between the study’s publication and November 2007, when Bayer removed the drug, “There were approximately 431,000 patients who received the drug,” Mangano. “As I calculated, 22,000 lives could have been saved. It’s about a 1,000 lives per month.”

Legal Help

If you or a loved one were injured by Trasylol, you have valuable legal rights. Please fill out our online form or call 1-800-LAW-INFO (1-800-529-4636) for a free consultation with an experienced Trasylol injury lawyer at our firm.