The new study, as reported by Forbes.com, includes an examination of Trasylol use in 49 randomized clinical trials, and also includes new information from the Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) study, published earlier this year. The findings of the new study, which was conducted by Canadian and Australian reserachers, will be published in the Jan. 20 issue of the Canadian Medical Association Journal.

Trasylol had been used extensively since 1987, and was only pulled from the U.S. market by manufacturer Bayer in November 2007. It seems incredible that a product that recent tests have proved significantly more dangerous than other similar drugs could have flown under the radar for 20 years.

The BART study revealed that patients treated with Trasylol were 53 percent more likely to die than patients treated with similar drugs. The study compared Trasylol (aprotinin) with two other drugs, Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid).

The new Canadian-Australian study confirms the BART results, saying Trasylol carries a higher risk of death, and, to add insult to injury, a significantly higher price tag than its alternatives.

According to the Forbes report, some of the blame for Trasylol’s longevity in the marketplace is being placed on the U.S. Food and Drug Administration.

SOURCE: Trasylol Recall › Follow-up to Canadian BART study confirms Trasylol risks

The FDA cannot identify a patient population in which the use of Trasylol (aprotinin) outweighs the risk, Dr. John K. Jenkins, director of the FDA’s Office of New Drugs, said at an early morning news conference Monday.

However, he added, “The suspension will include a slow phase-out of Trasylol from the marketplace, to decrease the possibility of shortages of the alternative drugs.” And he added that Bayer could continue to supply the drug if physicians can identify specific patients who would benefit from it.

“Studies have found that Trasylol can increase the risk of kidney damage compared with other drugs,” Dr. Gerald Dal Pan, the FDA’s director of the Office of Surveillance and Epidemiology, said during the news conference.

In 2006, he added, the FDA limited the use of Trasylol and strengthened its warnings. Subsequently, he said, studies found that Trasylol increased the risk of in-hospital death among patients undergoing cardiac bypass surgery. In addition, Dal Pan said, two studies this year found that the drug increased the long-term mortality of patients who had undergone bypass surgery.

The suspension follows news last month that a major Canadian trial of the drug was terminated because of an increase in deaths for cardiac surgery patients using it.

The trial was designed to show that Trasylol was better than other drugs in controlling bleeding, Dal Pan said. “That study was halted because Trasylol appeared to increase the risk for death compared with two other drugs,” he said.

Based on these findings, the FDA requested last week that Bayer suspend Trasylol pending further review, Dal Pan added.

In a company statement on its Web site Monday, Bayer stressed that the suspension was temporary. “Bayer believes that the totality of the available data continue to support a favorable risk-benefit profile for Trasylol when used according to labeling,” the statement said.

The FDA also said Monday that it plans to do a detailed review of the preliminary results from the Canadian trial before deciding whether to allow Trasylol back on the U.S. market.

Trasylol was first approved by the FDA in 1993, and has had a checkered history since then.

In the Canadian trial, called BART, an elevated 30-day and overall death risk caused the study’s Data Safety Monitoring Board (DSMB) to recommend stopping patient enrollment. The trial had been set to recruit about 3,000 adults who were candidates for a variety of cardiac surgeries and were at high risk of bleeding.

On Sept. 12, a U.S. Food and Drug Administration advisory panel recommended that Trasylol remain on the market, despite mounting evidence that it might have serious side effects.

In February, a study published in the Journal of the American Medical Association found patients on the drug were at greater risk of dying over the next five years than those given two other medications. The same researchers had linked the drug to an increased risk of kidney failure, heart failure and stroke in a study published in 2006.

“Our present findings deal with death,” one of the JAMA study’s authors, Dr. Dennis T. Mangano, said at the time. Mangano, director of the Ischemia Research and Education Foundation, a California-based nonprofit group, said that “the death rate for aprotinin patients far outstrips that for the other two drugs.”

His team’s study tracked the long-term survival of nearly 3,900 heart patients who underwent coronary artery bypass surgery at 62 medical centers worldwide. The researchers tabulated survival at six weeks, six months, and then annually for five years.

The five-year death rate for patients given Trasylol was 20.8 percent, compared to 15.8 percent for those given another drug, aminocaproic acid, and 14.7 percent for those given tranexamic acid. Both alternative drugs are available in generic versions.

After the 2006 report from Mangano’s group, the FDA advised doctors to carefully monitor Trasylol patients for kidney, heart and brain damage — an action taken after Bayer disclosed study data showing that it increased the risk of death, kidney damage, congestive heart failure and stroke.

The drug does have its defenders.

Dr. T. Bruce Ferguson Jr., associate director of cardiothoracic and vascular surgery at East Carolina University, wrote an accompanying editorial to the JAMA study. He said he believed the study “was inadequate to address the question they were asking because of the way the database was designed.”

“The most important factor they were unable to control was why patients got aprotinin,” Ferguson said. “There were no data to address that issue, and therefore it cannot account for physician-related bias.”

For example, the higher rate of death and other complications linked to the drug might be due to aprotinin being prescribed for “higher-risk patients who could be expected to have a worse outcome and higher mortality,” Ferguson said. Other studies have shown that “in carefully selected patients, aprotinin is a good drug,” he said.

The information used in the study was thorough and complete, Mangano countered. “In terms of the database, we had between 7,000 and 10,000 pieces of data per patient from 59 centers in 16 countries, including 23 of the 25 top cardiac centers in the United States,” he said.

“The findings speak for themselves,” Mangano added. “I think they are as accurate as you can get.”

He believes that the drug’s use should be restricted to about 5 percent of patients in whom other drugs could not be used.

SOURCE: Trasylol Recall › Trasylol Pulled From Worldwide Market

Known as BART, the study randomly administered one of three drugs to the patients: Trasylol, Cyklokapron (tranexamic acid) and Amicar (aminocaproic acid).

BART sought to answer questions about Trasylol’s safety and efficacy, despite the fact that the drug has been in use for over twenty years. Was Trasylol more effective than alternative drugs in controlling bleeding during cardiac surgery? And, how did rates of death, organ failure, and other serious complications measure in Trasylol compared to the alternative drugs?

Experts conducting the study found that Trasylol’s safety risks were so high, they ended the trial before its scheduled completion. Death rates among Trasylol patients were alarmingly higher than in patients who were given the alternative therapies. Dr. Paul C. Herbert, a critical care physician at Ottawa Hospital and one of the lead investigators, told BusinessWeek magazine that Trasylol represented a 53% increase in risk in dying compared to the other drugs. That “translates into for every 50 patients treated with aprotinin, one patient would die,” he explained.

Strangely, earlier Trasylol tests were small and not designed to study death. Information about the drug’s toxicity in some patients, therefore, remained hidden.

Dr. Eric J. Topol, director of the Scripps Translational Science Institute and dean of the Scripps School of Medicine, reacted to the results of BART with the same frustration as many North American consumers. In remarks made to BusinessWeek magazine, he wondered “why it takes so long for the truth to come out.”

“How many patients were lost because of this misadventure in therapeutics?” he asked.

SOURCE: Trasylol Recall › One in fifty Trasylol patients dies

Beginning immediately, Trasylol will belong to a class of drugs that require a special protocol for use. Patients who are at a high risk for blood loss during coronary artery bypass graft surgery may receive Trasylol if no alternative therapies are appropriate. In such cases, physicians must follow a special treatment protocol and submit it to the FDA for approval. The physician must show that the benefits of administering Trasylol outweigh the risks.

Trasylol is an antifibrinolytic drug that reduces excessive bleeding by slowing the breakdown of blood clots during heart surgery. In October 2007, the Data Safety Monitoring Board (DSMB) recommended the discontinuation of patient enrollment in a randomized Canadian study of aprotinin. The study was stopped once data suggested an increased risk of death in patients who had received Trasylol.

The FDA will reassess its special treatment protocol for Trasylol once it receives and has reviewed data from the study’s researchers. According to the FDA’s statement, “the FDA oversight requires comprehensive and thorough studies of a drug not only during the pre-market review phase but throughout the drug’s life cycle.” Many critics of the FDA object to the administration’s method of drug approval, which, they argue tests effectiveness of new medicines but not safety.

SOURCE: Trasylol Recall › FDA announces withdrawal of remaining Trasylol