Cardiac Surgery Drug Increases Death Rate

A large study of aprotinin, a drug used to limit bleeding during cardiac surgery, has shown that it increases death rates and damages kidney function.

Researchers at Duke University Medical Center (Durham, NC, USA) collected prospective data on 10,275 patients who underwent coronary-artery bypass surgery (CABG) between 1996 and 2005; 1181 of them also underwent valve surgery. Of these, 1,343 patients (13.2%) received aprotinin, 6776 patients (66.8%) received aminocaproic acid (another drug used to limit bleeding), and 2029 patients (20.0%) received no therapy. The researchers analyzed the data in a logistic-regression model predicting each patient's likelihood of receiving aprotinin on the basis of preoperative characteristics and to models predicting long-term survival (up to 10 years) and decline in renal function, as measured by increases in serum creatinine levels.

The researchers found that in the risk-adjusted model, survival was worse among patients treated with aprotinin, with a main-effects hazard ratio for death of 1.32 when compared with patients receiving no antifibrinolytic therapy, and 1.27 for the comparison with patients receiving aminocaproic acid. The study also found that patients who received either aminocaproic acid or no therapy did not have the high rates of poor kidney function seen in the aprotinin group, but did not have a greater risk-adjusted incidence of dialysis. The study was published in the February 21, 2008, edition of The New England Journal of Medicine (NEJM).

"We were looking for an association between exposure to the drug and subsequent adverse outcomes,” said lead author Dr. Andrew Shaw, M.D., an associate professor in the department of anesthesiology. "We found an increased incidence of death in patients who received aprotinin. That higher death rate seemed to persist even when we were able to control for the differences seen between the patient groups.”

Aprotinin, a drug manufactured by Bayer (Leverkusen, Germany) that gained U.S. Food and Drug Administration (FDA) approval in 1993, was temporarily suspended from marketing in the U.S. in November 2007 after the Canadian BART (Blood conservation using antifibrinolytics) study (also published in the NEJM), found similar findings. The drug is used routinely during cardiac surgery, particularly on high-risk patients, to reduce bleeding and the need for blood transfusion. According to previously published research, patients undergoing cardiac surgery receive approximately one fifth of all the red cell transfusions in the United States, and each unit transfused is known to increase the risk of infection.


Related Links:
Duke University Medical Center
Bayer