Study Questions Risks Of Anti-bleeding Drug During Heart Surgery

"Our study is important because it shows that if aprotinin is used selectively and a drug/lab test interaction is avoided, the drug does not hurt patients' hearts or brains while reducing their need for blood transfusions and reoperations for bleeding," said C. Michael White, Pharm.D., of Hartford Hospital in Hartford, Conn., one of the study authors.

The study was prompted by recent reports suggesting an increased risk of complications--including heart attacks, strokes, and kidney problems--in patients who received aprotinin to reduce bleeding during heart bypass or valve replacement surgery. In response, the U.S. Food and Drug Administration issued an alert limiting the use of aprotinin during heart surgery.

Dr. White and colleagues performed a similar study, but limited to patients treated at Hartford Hospital, where aprotinin was used differently than at most other hospitals. "We thought our results might be different than what most hospitals had seen, because at Hartford Hospital, we reserved drug therapy to patients who would most benefit and we avoided a drug/laboratory test interaction that could have resulted in an increased risk of blood clots," according to Dr. White.

The analysis included 3,348 patients undergoing bypass or valve replacement surgery at Hartford Hospital from 2000 through 2005. In contrast to the previous study, there was no increase in heart attack risk among patients receiving aprotinin, while the risk of stroke was 35 percent lower.

As in the previous study, patients receiving aprotinin had an increased risk of kidney dysfunction after surgery. It was not clear whether the kidney problems were permanent or temporary.

One reason for the conflicting results is that Hartford Hospital limited the use of aprotinin to patients undergoing particularly complex operations (and to patients like Jehovah's Witnesses, who refuse blood transfusions).

Another reason was that the Hartford Hospital doctors avoided a specific lab/drug test interaction that can lead to inadequate anti-clotting treatment. "During bypass or heart valve surgery, patients receive a drug called heparin to prevent blood clot formation," Dr. White explained. "Surgery teams know how much to give because they measure the activated clotting time (ACT). Previous studies have found that aprotinin makes the ACT rise erroneously if celite-ACTs are used. If you are using celite-ACTs to guide heparin dosing in a patient treated with aprotinin, you will think you gave enough heparin when in fact you didn't." This interaction may explain some of the increased risks with aprotinin reported in previous studies.

However, Dr White did not want to dismiss the importance of the previous studies showing harm. "Those studies were important, because they clearly showed that the way aprotinin was used around the world, by and large, was hurting patients more than helping them," said Dr. White. "By using aprotinin selectively and avoiding the celite-ACT test, surgical teams can reduce the risk of bleeding problems during surgery without increasing the risks of heart attack or stroke."