The New England Journal of Medicine reports about the recent drug Trasylol.
September 30 is becoming a day of infamy for drug safety. On that date in 2004, Merck announced that rofecoxib (Vioxx) doubled the risk of myocardial infarction and stroke, and the company withdrew the drug from the market after 5 years of use in more than 20 million patients. On September 30, 2006, a front-page article in the New York Times reported that the Food and Drug Administration (FDA) had issued a warning that the antifibrinolytic drug aprotinin, widely used to reduce perioperative bleeding in patients undergoing cardiac surgery, could cause renal failure, congestive heart failure, stroke, and death.
Some experts had been concerned about aprotinin (Trasylol) ever since its approval in 1993.1 As Hiatt explains in his Perspective article in this issue of the Journal (pages 2171–2173), one of two epidemiologic studies reported early this year provided support for this concern. In an observational study involving 4374 patients who underwent coronary revascularization,2 Mangano et al. found that patients who were given aprotinin had an incidence of postoperative renal failure requiring dialysis that was more than twice that among patients who received different agents. Among patients undergoing uncomplicated coronary-artery surgery, those given aprotinin had a 55% increase in the incidence of myocardial infarction or heart failure and a 181% increase in the incidence of stroke or encephalopathy. The authors advised against further use of the drug, since safer, cheaper alternatives are available.
After the study was published, the FDA moved to convene an advisory committee to reassess the drug’s safety and assembled the relevant data. The committee met on September 21, reviewed the available evidence, and concluded that there was no need for additional warnings on the drug’s official labeling.
What put aprotinin on the front page on September 30, however, was the revelation that its manufacturer, Bayer, had hired a private contract research organization to perform its own large observational study of postoperative complications in patients given the drug. The analysis, completed in time for the FDA meeting, reached conclusions similar to those of Mangano et al. It, too, adjusted for a wide variety of clinical characteristics and showed that patients who received aprotinin had higher mortality rates and substantially more renal damage than those given other treatments. But neither Bayer nor its contractor had provided the report to the FDA or even acknowledged its existence before the meeting.