Wednesday, February 20, 2008

Drug used in cardiac surgery increases mortality rate, DCRI researchers confirm
By Kelly Winget

A small Canadian study found that a drug used during cardiac surgery to limit bleeding actually damages the kidney and increases patients' death rates. Now the largest study done to date on the drug, led by Duke and DCRI researchers, has confirmed this.

Aprotinin, marketed as Trasylol, was temporarily prohibited from sales in the U.S. in November 2007 after the findings from the first study had been released.

“We're not surprised by the results,” said Andrew Shaw, MB, associate professor of Anesthesiology/Cardiac Division and the lead author of the paper which appears in the February 21 edition of the New England Journal of Medicine . “It's what we expected to find.”

The Duke study is more than twice as large as any other study done on aprotinin. Researchers analyzed data on more than 10,000 patients who had cardiac bypass surgery between 1996 and 2005, when the drug was considered to be safe. A study published in a 2006 issue of the New England Journal of Medicine that found that aprotinin increased the risk of heart attack, stroke and serious kidney damage prompted the Duke research team to analyze its database of patients.

Researchers analyzed the data to see if there was a correlation between receiving the drug and an increase in adverse outcomes. There was a higher death rate among patients who received aprotinin, and this persisted when researchers were able to control for differences between patient groups.

They also found that patients who had received aprotinin had higher serum creatinine levels, an indication that their kidneys were not filtering waste products adequately.

Of the 10,275 patients the researchers reviewed, 13 percent received aprotinin, 67 percent received aminocaproic acid to limit bleeding and 20 percent did not receive either of the drugs. The patients who received aminocaproic acid and the patients who were not administered a drug to limit bleeding did not have the same high death rates or poor kidney function that researchers found in the aprotinin group.

Aprotinin was approved by the Food and Drug Administration in 1993 and was routinely used during cardiac surgery to reduce bleeding and decrease the need for a blood transfusion. The drug was frequently used for high-risk patients. Cardiac surgery patients receive approximately one-fifth of all red blood cell transfusions in the U.S. , and each blood transfusion increases the risk of infection.

The study doesn't address the possibility of the increased mortality rate resulting from a greater number of high-risk patients receiving the drug. Researchers said this study did highlight the importance of conducting observational studies on drugs that are widely used. They added that further study into aprotinin might be necessary.