Popular heart surgery drug linked to heart attacks

Clotting drugs like Trasylol are given to some patients during heart surgery to reduce bleeding.

The study findings suggest that two other drugs -- aminocaproic acid and tranexamic acid -- work just as well as Trasylol in controlling bleeding, but are safer and cheaper due to the availability of generic versions.

In an interview with Reuters Health, lead author Dr. Dennis T. Mangano likened the potential scenario with Trasylol, produced by Bayer AG, to what happened with Vioxx, Merck's COX-2 inhibitor that was pulled from the market in September 2004 after being tied to MI and stroke.

"It's a 'Vioxx 2,' but it's a little bit different," Mangano, from the Ischemia Research and Education Foundation in San Bruno, California, said. "The frequency of (adverse) events we see is far greater with (Trasylol) than with Vioxx. The other thing that is disturbing is that the drug has been in use for 13 years and a million patients have received it. Why am I coming along now and finding these results and why haven't they been found before?"

The new study, which Dr. Mangano called the biggest study to investigate aprotinin, included 4,374 heart surgery patients who received Trasylol, aminocaproic acid, tranexamic acid or no agent.

A total of 3,013 patients underwent surgery to open a blocked coronary artery and 1,361 underwent more complex procedures. In the former group, Trasylol use significantly increased the risk of heart attack, stroke and kidney failure compared with patients who received no treatment. In the latter, the drug was associated with an increased risk of renal failure only.

None of these increased risks were seen with aminocaproic acid or tranexamic acid, but both drugs were similar to Trasylol in reducing bleeding.

Mangano said that if a doctor elects to use Trasylol and the patient develops kidney failure or another complication, his actions are going to be hard to defend.

In a statement released to Reuters Health, Bayer AG commented that the findings "are not consistent with the more than 15 years of clinical data and experience Bayer has amassed on this drug." Bayer emphasized that a randomized trial "is the accepted standard for the assessment of the efficacy and safety of drugs," not the observational type of study used by Mangano's group.

Anticipating this criticism, Mangano "said that once you have an embedded practice with a drug you cannot easily do a randomized trial to assess drug safety." He added that "he expects Bayer to put up a battle. You don't get a $600 million per year drug, well on its way to a blockbuster, and give it up easily."

In a related commentary, Dr. David Hunter, a statistician from the Harvard School of Public Health in Boston, notes that observational studies may provide "the only source of evidence on the side effects of drugs" and calls the research by Mangano's team "the type of study that may be a model for the future." He goes on to list several reasons why observational studies may be better suited to uncovering side effects than are randomized trials.

SOURCE: The New England Journal of Medicine, January 26, 2006.