Bayer Halts Sale of Drug Used in Heart Surgery
Trasylol Linked to Deaths After Procedure

By Rob Stein
Washington Post Staff Writer
Tuesday, November 6, 2007

Under pressure from government regulators around the world, Bayer announced yesterday that it is suspending global sales of a drug widely used to control bleeding during heart surgery, after a study found that patients receiving the medication were at increased risk of dying compared with those who received two other drugs.

U.S., German and Canadian regulators pushed Bayer to stop selling Trasylol until authorities could complete a detailed review of a Canadian study that was halted two weeks ago when a preliminary analysis indicated that those given the medication were more likely to die in the 30 days after the procedures.

Because there are only two other drugs available for such patients, the Food and Drug Administration said it would work with the company to slowly phase out Trasylol to make sure hospitals have the adequate supplies of the alternatives. The agency also left open the possibility that the drug may be permitted for specific patients if doctors can identify those for whom the benefits outweigh the risks.

At present, however, the FDA "cannot identify a specific patient population where we believe the benefits outweigh the risks," said John K. Jenkins, director of the FDA's office of new drugs.

Bayer said that it is working with the FDA, the German Federal Institute for Drugs and Medical Devices, and Health Canada but that the medication can be used safely.

"Bayer believes that the totality of the available data continue to support a favorable risk-benefit profile for Trasylol when used according to labeling," the company said in a statement.

More than 4.77 million patients have received the drug since it was approved in 1993. In 2006, approximately 110,000 U.S. patients and 87,000 patients outside of the United States received Trasylol, the company said. The FDA did not have any estimates for how many deaths the drug may have caused.

The announcement culminates mounting concerns about the drug, also known as aprotinin. The drug was approved to minimize bleeding in patients undergoing bypass surgery, one of the most common procedures.

The first red flag went up in January 2006 after two studies found that Trasylol increased the risk of kidney damage, heart failure, heart attacks and strokes. That prompted the agency to convene a panel of experts to review the drug's safety, and based on its recommendations, the FDA restricted use of Trasylol and added new warnings to its label.

But the FDA subsequently learned that Bayer had failed to inform the advisory panel or the agency about another study that showed the drug might be linked to increased deaths. That prompted the agency to issue an unusual public health advisory and convene another panel of experts in September. That committee said more data were needed.

The agency finally asked the German company to suspend sales after the Ottawa Health Research Institute halted a study designed to compare Trasylol with two other drugs in 2,970 patients undergoing multiple types of heart surgery. An independent board monitoring the study analyzed preliminary data from 2,163 patients and found a trend toward an increase in mortality in those receiving Trasylol. If confirmed in the final analysis, this trend would translate into approximately two additional deaths per 100 patients receiving the drug, the researchers said.

Jenkins defended the FDA's handling of the issue, pointing to the two advisory panels that recommended the drug remain on the market.

"It's important to recall what this drug is approved for. It is approved to reduce serious bleeding in patients undergoing cardiac surgery where bleeding can be serious, even life-threatening," Jenkins said.

Bayer estimates worldwide sales of the drug were roughly $135 million for the nine months through September. The United States accounted for about $91 million.

"Once the complete . . . data set is available, Bayer will work with health authorities to evaluate whether these data have any impact on the positive benefit-risk assessment for Trasylol. At that time the temporary marketing suspension will be re-evaluated," the company said.