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Drug used in coronary artery bypass graft surgery may increase risk of death

February 07, 2007

Aprotinin, a drug used for limiting blood loss in patients undergoing cardiac surgery, is associated with an increased risk of death during five years following the surgery, according to a new study in the February 7 issue of JAMA.

Aprotinin was first approved for use in high-risk patients needing coronary artery surgery in the United States in 1993. As background information in the article, the authors state that more than 4 million patients worldwide have received aprotinin since 1985, principally during cardiac surgery. Annual use has increased to 600,000 patients (2005) throughout the world, including 246,000 uses in the United States in the past year. The safety of aprotinin came under scrutiny in 2006. An "observational study reported that aprotinin use was associated with a doubling to tripling of the risk of perioperative renal [kidney] dysfunction and failure requiring dialysis in patients undergoing primary, repeat or complex coronary artery surgery."

Dennis T. Mangano, Ph.D., M.D., from the Ischemia Research and Education Foundation, San Bruno, Calif., and colleagues assessed survival rates at six weeks, six months and annually for five years for 3,876 patients undergoing coronary artery bypass graft (CABG) surgery at 62 medical centers around the world. The researchers examined death rates of these patients according to the use of three medications used to lessen bleeding—aminocaproic acid and tranexamic acid, aprotinin, or no anti-bleeding agent.

"During five years, 223 deaths occurred among 1,072 aprotinin-treated patients (20.8 percent), a death rate nearly two-thirds greater than control patients (128 deaths among 1,009 patients, 12.7 percent)," the researchers found. "Rates were similar for aminocaproic acid patients (132 deaths among 834 patients, 15.8 percent) and for tranexamic acid patients (65 deaths among 442 patients, 14.7 percent)."

"We estimate that over the past year, aprotinin was prescribed worldwide to at least 200,000 cardiac surgery patients having a profile similar to patients in our study. For such patients, our study found a 5-percent absolute increase in five-year mortality (1 percent per year for five years) associated with aprotinin use, compared with either aminocaproic or tranexamic acid use."

"These findings indicate that in addition to the previously reported acute renal and vascular safety concerns, aprotinin use is associated with an increased risk of long-term mortality following CABG surgery. Use of aprotinin among patients undergoing CABG surgery does not appear prudent because safer and less expensive alternatives (i.e., aminocaproic acid and tranexamic acid) are available," the authors conclude.

JAMA and Archives Journals