Taking on Trasylol

San Bruno, CAIn medicine, some of the most hard-hitting drug research often comes from organizations far removed from the healthcare mainstream. Take the case of Trasylol, for example.

Trasylol is the brand name for Aprotinin, a drug approved by the U.S. Food and Drug Administration in 1993 to reduce bleeding during heart surgeries. Trasylol is made by pharmaceutical giant Bayer—an international conglomerate comprised of 106,000 employees working in 350 companies around the world, with its headquarters in Leverkusen, Germany.

In 2006 and 2007, the Ischemia Research and Education Foundation (IREF) published back-to-back studies that offered devastating critiques of Trasylol's safety record. The first study demonstrated that Trasylol doubled the risk of kidney failure in patients. The second study indicated the drug increased the risk of death.

Based out of San Bruno, California, IREF is a self-described, "independent, non-profit biomedical research organization founded in 1987 and dedicated to performing quality medical and scientific research that saves and extends lives."

IREF works closely with a companion organization called the Multicenter Study of Perioperative Ischemia (McSPI) Research Group, which was founded in 1989. Ischemia refers to the reduction of the blood supply to parts of the human body. A researcher named Dr. Dennis Mangano founded both organizations.

"The broad IREF/McSPI Investigator Network ... is now composed of nearly 300 research centers around the world, representing leading institutions and scientists," explains the iref.org website. "The goodwill and collaboration of these centers over time allows us to provide a cohesive, matured system for the accumulation of large-scale databases as well as rapid commencement, conduction and completion of complex U.S. and global clinical trials."

In January 2006, IREF released the results of what it called "the first comprehensive, observational non-industry sponsored analysis of Aprotinin's safety." The results—which were published in the New England Journal of Medicine—were not pretty.

According to IREF, the study proved that Aprotinin "doubled a patient's risk of kidney failure and increased the risk of heart attack, heart failure and stroke."

"Our study provides compelling evidence of Aprotinin's serious risks, and strongly suggests discontinuation of use and replacement with either of the two alternative generic and far less costly medications proven safe in this study," Dr. Mangano was quoted as saying in an IREF press release.

To conduct their study, IREF researchers examined data from 4,374 patients around the world who were receiving either Aprotinin or one of two generic equivalent drugs.

Using the same data, IREF came to an even more shocking conclusion in a follow-up study one year later. Use of Aprotinin "has now been proven to increase a patient's risk of dying during the first five years after cardiac surgery," announced an IREF press release from February 2007.

"Over the past 20 years, more than four million patients worldwide have received Trasylol and in the United States, approximately 246,000 had received it in 2005," stated the press release.

"Had Aprotinin been replaced with either of the two safer generic drugs, even for one year, as many as 2,000 deaths per year over the subsequent five years (or 10,000 deaths overall) could have been avoided, with savings of at least $1 billion in healthcare costs and at least $250 million in drug costs."

The results of this latest study were published in the Journal of The American Medical Association (JAMA).

This latest attack on Trasylol triggered the ire of the mighty Bayer empire. In a press release from February 2007, Bayer blasted the IREF's research techniques. Among other things, Bayer said IREF researchers examined patients based all over the world, who might be receiving different levels of care.

Bayer made some sound points but most observers would draw a different lesson: IREF proved that it's possible for an independent David to draw blood from a medical Goliath, no matter how many resources the latter has on their side.