TUESDAY, Feb. 6, 2007 (HealthDay News) -- Patients given aprotinin, a drug used to limit blood loss in heart bypass surgery, are at greater risk of dying over the next five years than those given two other medications, a new study finds.
The report, published in the Feb. 7 issue of the Journal of the American Medical Association, comes from the same group that last year linked aprotinin to an increased risk of kidney failure, heart failure and stroke.
"Our present findings deal with death," said study author Dr. Dennis T. Mangano, director of the Ischemia Research and Education Foundation, a California-based nonprofit group. "The death rate for aprotinin patients far outstrips that for the other two drugs."
The 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 aprotinin 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.
Aprotinin was approved for use in high-risk cardiac surgery patients by the U.S. Food and Drug Administration in 1993. After last year's report from Mangano's group, the FDA advised doctors to carefully monitor aprotinin patients for kidney, heart and brain damage -- an action taken after Bayer Pharmaceuticals, which markets the drug as Trasylol, disclosed study data showing that it increased the risk of death, kidney damage, congestive heart failure and stroke.
The FDA has taken no further action since then, and "what they will do with this new data is beyond me," Mangano said. "A more important indicator is whether or not surgeons are going to use it."
Last year's report led to a 37 percent reduction in surgeons' use of aprotinin, Mangano said. "Clinicians, more than anyone else, will decide whether this drug should be on the market or its use should be limited," he said.
Aprotinin 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 new study. He believes 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."
"The findings speak for themselves," Mangano said. "I think they are as accurate as you can get."
He believes that aprotinin's use should be restricted to about 5 percent of patients in whom other drugs could not be used.
"And the surgeon would have to tell each patient before using this drug that there is literature out there showing that this drug is associated with renal [kidney] failure and death," Mangano said. "For the vast majority of patients, there are the two other alternatives."
There's more on cardiac surgery at the U.S. National Library of Medicine.