Rockville, MD - The US FDA has issued a public-health advisory alerting doctors who perform cardiac bypass surgery and their patients to two studies suggesting serious adverse events with aprotinin (Trasylol, Bayer), which is used to prevent blood loss during surgery.

One of the studies, reported last month in the New England Journal of Medicine, showed that patients who received aprotinin had higher rates of renal failure, MI, and stroke compared with those treated with other drugs to prevent bleeding or with no treatment [1]. The second study, reported online in Transfusion on January 20, 2006, reported more cases of decreased kidney function in patients treated with aprotinin compared with another treatment to prevent bleeding [2].

The FDA points out that both studies have the limitation of being observational, which prevents a direct assessment of whether aprotinin altered the risk for serious adverse events, even though statistical methods to adjust for possible differences in patient risk factors were used.

The agency says it is evaluating these studies, along with other studies in the literature and reports submitted to the FDA through the MedWatch program, to determine whether labeling changes or other actions are warranted.  

It notes that in premarketing randomized, placebo-controlled clinical studies conducted among approximately 3000 patients undergoing CABG, the risks for serious renal toxicity and cardiovascular events were determined to be similar between patients receiving aprotinin and those receiving placebo. However, in one study assessing coronary graft patency, aprotinin was associated with an increased risk of graft closure.  

The FDA says it will work with the authors of the papers and with Bayer to carefully evaluate the risks and benefits associated with use of aprotinin in CABG, and an advisory committee meeting will be held in the near future to discuss the data.

In the meantime, the agency makes the following recommendations:

• Physicians who use Trasylol should carefully monitor patients for the occurrence of toxicity, particularly to the kidneys, heart, or central nervous system, and promptly report adverse-event information to Bayer or to the FDA MedWatch program.
• Physicians should consider limiting Trasylol use to those situations where the clinical benefit of reduced blood loss is essential to medical management of the patient and outweighs the potential risks.

The FDA notes that aprotinin is the only product approved in the US for the prevention of perioperative blood loss and the need for blood transfusion among patients undergoing CABG. It does not mention other possible alternatives that may be used instead of aprotinin, such as aminocaproic acid and tranexamic acid, which were not associated with any safety issues in the recent NEJM study.