Raising fresh concerns about a widely used heart-surgery medicine, a study released Tuesday reported that the drug Trasylol increased patients' long-term risk of dying by nearly 50%.
An estimated 10,000 deaths worldwide could be avoided over the next five years if Trasylol were not used, according to the report in the Journal of the American Medical Assn.
The study, funded by the San Bruno, Calif.-based Ischemia Research and Education Foundation, said Trasylol was unnecessary for most patients because safer and cheaper alternatives were available. The drug, also known by its generic name, aprotinin, is used to control bleeding during open-heart surgery.
Dr. Dennis T. Mangano of the foundation and lead author of the study said Trasylol should be restricted to patients with the highest risk of bleeding complications.
"I would use this drug as a last resort," he said.
But an editorial in the journal accompanying the study, written by Dr. T. Bruce Ferguson Jr. of the Brody School of Medicine at East Carolina University, said the study could not be considered conclusive because it was an observational study that tracked patients after they had been treated. The gold standard is a clinical trial in which patients are randomly assigned to specific treatment groups.
The study was the latest to question the safety of Trasylol, which was approved by the Food and Drug Administration in 1993.
Last year, Mangano and other researchers linked Trasylol to a higher risk of kidney failure, heart attack, heart failure and stroke. Following that report, which was published in the New England Journal of Medicine, the FDA added a warning about kidney failure to Trasylol's product label.
Responding to the latest study, the FDA said it would include the new findings in an ongoing safety review of Trasylol, which could lead to labeling changes or other actions.
Trasylol was used in 200,000 cardiac bypass surgeries worldwide last year, according to the report, a substantial decline from 2005, when the drug was used in 600,000 surgeries. About 1 million bypass surgeries are performed worldwide each year.
"Many surgeons have stopped using it entirely," said Dr. Alfredo Trento, chairman of cardiothoracic surgery at Cedars-Sinai Medical Center. "If something happens to a patient and you have used Trasylol, it is an uncomfortable position to be in."
The study examined records on nearly 3,900 patients who had heart bypass surgery at 62 medical centers in 16 countries. Researchers compared patients who received Trasylol with those who received an alternative drug to control bleeding or took no drug at all.
After five years, 20.8% of patients who received Trasylol died, compared with 12.7% who received no medicine. After making adjustments to account for patient differences and other factors, those who received Trasylol had a 48% higher risk of death over five years compared with patients who received no drugs to control bleeding, researchers said.
Patients who received one of the alternative drugs, aminocaproic acid or tranexamic acid, faced no additional risk of death. The disadvantages of Trasylol remained after accounting for confounding factors such as diabetes or high blood pressure, researchers said.
It wasn't clear why Trasylol's increased risks lingered for five years. The drug prevents bleeding in surgery patients by blocking a protein that dissolves clots. Mangano said it was possible that the drug allowed small clots that formed during surgery to persist. Over time, these clots could become large enough to block an artery, causing a heart attack or stroke, he said.
Bayer, the German drug company that markets Trasylol, said in a statement that the statistical methodology used in the study to account for health differences among patients was "not reliable." In addition, the study did not account for differences in clinical practices across countries, Bayer said.
The company's handling of safety concerns about Trasylol caused a stir in September, when it failed to provide to the FDA a study detailing serious health risks.
Two weeks ago, Bayer stopped three clinical trials of Trasylol in non-cardiac patients, a decision the company said was unrelated to safety concerns.