Rockville, MD - Increasing mortality throughout the first 30 days of a randomized trial among surgical patients who received aprotinin (Trasylol, Bayer), compared with other antifibrinolytic agents, has put the brakes on further enrollment, announced the US Food and Drug Administration, which said it received the news on October 19, 2007 from the study's data safety monitoring board [1]. Signs that the drug may present an untoward risk have been reported frequently.

In the Canadian Blood Conservation Using Antifibrinolytics: A Randomized Trial in a Cardiac Surgery Population (BART), which included patients undergoing various types of surgery who were at increased risk for bleeding complications, the apparent aprotinin risk hadn't reached statistical significance but was judged unlikely to improve.

BART had been designed to determine whether aprotinin would be better than either epsilon-aminocaproic acid or tranexamic acid in preventing "massive bleeding" associated with cardiac surgery, the announcement said.

Aprotinin is currently approved for preventing perioperative blood loss and cutting the need for transfusions during pump-supported CABG surgery in high-risk patients, according to the agency. "In light of the preliminary BART study findings, the FDA anticipates reevaluation of the overall risks and benefits of Trasylol. This reevaluation may result in the need to revise the labeling or other regulatory actions," it noted. For now, it said, healthcare providers should be mindful of accumulating data suggesting aprotinin can increase mortality compared with the other antifibrinolytics. 

The announcement closely follows the publication of a massive meta-analysis of randomized trials suggesting that aprotinin does not raise the risk of operative thrombosis or death [2] and comes on the heels of recommendations from two FDA advisory committees to keep the drug on the market.

The meta-analysis, lead author Dr David A Henry (Institute for Clinical Evaluative Science, Toronto, ON) had told heartwire at the time, was "reassuring on safety," although it couldn't rule out an adverse effect on renal function. He had also pointed to BART as a forthcoming study that should help clarify the relative safety, efficacy, and cost-effectiveness of the different antifibrinolytics.