According to a report on 60 Minutes, the delay in taking Trasylol off the market after the publication of Dr. Dennis Mangano's groundbreaking study showing elevated risks of kidney damage (including dialysis), heart attack and stroke may have cost 22,000 lives. Dr. Mangano estimates that as many as 1,000 people per month died as a result of the use of Trayslol during Coronary Artery Bypass Graft surgery from the publication of his article in January, 2006 until the drug's withdrawal in November of 2007.
On February 21 2008, two studies were published in the New England Journal of Medicine. Both studies confirmed that Trasylol causes an increased risk of death and kidney damage compared to alternative medicines or no medicine at all. Trasylol is an antifibrinolytic agent used during cardiac surgery to reduce the risk of blood transfusions. However, for patients that require the use of such a medication, two alternatives exists - aminocaproic acid and tranexamic acid - both of which are substantially less expensive than Trasylol. According to the two most recent articles and Dr. Mangano's study, aminocaproic acid and tranexamic acid are equally effective in reducing the risk of needing blood transfusions due to blood loss but present none of the health problems that Trasylol presents.
According to the February 2008 article by Dr. Andrew Shaw, et al., "survival was worse among patients treated with [Trasylol], with a main-effects hazard ratio for death of 1.32 (95% confidence interval, 1.12 to 1.55) for the comparison with patients receiving no antibrinolytic therapy (P=0.003) and 1.27 (95% CI, 1.10 to 1.46) for the comparison with patients receiving aminocarpoic acid (P=0.004).
In addition to the Shaw article, an article by Dr. Schneeweiss, et al., is also being published in the New England Journal of Medicine this month. This is the study that was actually funded by Bayer and withheld from the FDA until after a pivotal Advisory Committee meeting on Trasylol. This study concludes that the risk of death is 64% higher with Trasylol compared to aminocaproic acid (relative risk, 1.64; 95% confidence interval, 1.50 to 1.78).
Trasylol is a drug used to control bleeding and limit the need for blood transfusions in patients undergoing Coronary Artery Bypass Grafting surgery. Several studies have linked Trasylol to a nearly doubling of the risk of kidney failure resulting in the need for dialysis. Because Trasylol is administered intravenously after the patient is under anesthesia, patients are unaware that they have received this dangerous drug.
Bayer failed to disclose the findings from its own research to the FDA that confirmed the drug increased the risk of these serious side effects. The study, conducted at Bayer’s request, examined the hospital records of 67,000 patients undergoing CABG procedures. About half of these patients received Trasylol while the other half received one of the cheaper, safer alternatives (one dose of Trasylol can cost upward of $1,400).
The study suggests that the patients who received Trasylol were at an increased risk for death, kidney failure, heart attack and stroke. Bayer had received the results of the study at the time of the FDA advisory board committee meeting held to discuss the safety of the drug, yet failed to mention the study’s existence or it’s results.
WEDNESDAY, Jan. 25 (HealthDay News) -- A widely promoted drug used to prevent bleeding during heart surgery doubles the risk of kidney failure and increases the risk of heart attack, heart failure and stroke, a study finds.
Two less expensive generic drugs used for the same purpose do not carry the same dangers, said a report in the Jan. 26 issue of the New England Journal of Medicine.
The study looked at data on 4,374 patients who had surgery after heart attacks and is "the largest study yet done," said Dr. Dennis T. Mangano, director of the Ischemia Research and Education Foundation, a California-based nonprofit organization, and lead author of the report.
It compared the outcomes of operations in which patients undergoing coronary artery surgery were given either one of three drugs to reduce bleeding: aprotinin, the newer agent; aminocaproic acid; tranexamic acid; or no drug at all.
The incidence of kidney failure in patients who got aprotinin was more than double that of those who got either of the two other drugs or no drugs at all, the report said. The risk of stroke was 181 percent higher, while the incidence of heart attack or heart failure was 55 percent higher.
The study was done because previous, smaller trials indicated an increased risk associated with aprotinin, but none of them was large enough to be definitive, Mangano said.
Aprotinin was approved by the U.S. Food and Drug Administration in 1993. It is marketed by Bayer HealthCare under the brand name Trasylol.
A statement from Bayer said it "has only just become aware of this observational study" and has not yet reviewed its findings. But the company said the reported increases in risks "are not consistent with the more than 15 years of clinical data and experience Bayer has amassed on this drug." Bayer said its claim of safety was based on controlled trials including almost 6,500 heart-surgery patients.
Mangano countered by saying those studies looked at the effectiveness of the drug, not at its safety. "There is no financial incentive for the drug industry to do safety trials after approval," he said.
And a study looking at safety "would find it very difficult to enroll patients," Mangano said. "You would be telling patients they would get a protein that promotes kidney failure."
The fact that aprotinin is a protein, while the other drugs are different chemically, could account for the reported kidney damage, he said. A protein is taken up by the kidney, where it remains for 24 hours and can change kidney function, Mangano said. He estimated that 10,000 Americans now require artificial kidneys because they were given aprotinin.
The Bayer statement said the new study was not the kind of randomized, controlled trial that is "the accepted standard for the safety and efficacy of drugs."
In an accompanying editorial in the journal, Dr. Gus J. Vlahakes of Massachusetts General Hospital said that "regulatory requirements and the desire to ensure approval often dominate the design of clinical trials."
The desire to get a drug approved quickly often leads to selection in trials of patients who are least likely to have adverse reactions, said Vlahakes, who is chief of cardiac surgery at the hospital. But once a drug is approved, the company is free to push for expanded uses, he said.
The new study shows the need for continued testing of drugs after their first approval, Vlahakes said. "This process of phase 4 testing [after approval] I think is very important and something the FDA might want to require," he said.
In the case of aprotinin, Bayer has proposed its use for all heart-surgery patients, saying the drug can prevent an inflammatory reaction often caused by use of a heart-lung machine during the operation, Vlahakes said. The results of the study "are a strong suggestion that you can't just put aprotinin in the repertoire for all patients," he said.
At Massachusetts General Hospital, heart-surgery patients are generally given one of the older drugs, with aprotinin used "only in select circumstances where we expect to have particular difficulty with bleeding," Vlahakes said. Experience has shown that half the recommended dose is fully effective, he said.
Heart drug may boost risk of death, FDA says
Nightly News with Brian Williams, U.S. - Feb 20, 2008
One Thousand Lives A Month
CBS News, U.S. - Feb 17, 2008
Researcher Estimates 22,000 Lives Could Have Been Saved Had Trasylol Been Pulled Earlier...
Canada NewsWire (press release), Canada - Mar 30, 2007
Trasylol(R) is a drug injected during heart bypass surgery to help reduce bleeding and the need for blood transfusions. - Trasylol(R) should only be used ...
Bypass Drug may Raise Death Rate
WFIE-TV, IN Feb 9, 2007
Nearly 21 percent of people who received aprotinin (Trasylol) died within five years of their surgery, compared to about 13 percent of those who didn't ...
Heart Surgery Drug Raises Death Risk, Study Finds
FOX News - Feb 7, 2007
The researchers said replacing the drug — aprotinin, sold by Bayer AG under the brand name Trasylol — with other, cheaper medications for a year would...
Newsinferno.com, NY - Feb 7, 2007
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 ...
Newsinferno.com, NY - Jan 27, 2007
Bayer HealthCare announced it is discontinuing three clinical trials for their drug, Trasylol, citing recent FDA-approved label changes. ...
Bayer Discontinues Trasylol(R) Clinical Trial Program In Non-CABG Indications
Medical News Today (press release), UK - Jan 26, 2007
Bayer HealthCare has decided to end three ongoing clinical studies investigating the safety and efficacy of Trasylol(R) (aprotinin injection) on transfusion ...