Fergusson DA et al. for the BART Investigators (2008) A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 358: 2319–2331

Randomized trials have demonstrated that three antifibrinolytic agents—the serine protease inhibitor aprotinin and the lysine analogs aminocaproic acid and tranexamic acid—reduce the need for blood transfusion in cardiac surgery. The data do not, however, support the definitive use of any one drug over the others. The Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) investigators aimed to establish whether aprotinin is superior to the other two agents in minimizing massive bleeding in patients undergoing high-risk procedures.

In this multicenter, blinded, randomized study, adult patients who were scheduled to undergo high-risk cardiac surgery, such as aortic procedures, valve replacement, or repeat CABG surgery, were randomly assigned to receive aprotinin (n = 780), aminocaproic acid (n = 780), or tranexamic acid (n = 770) during their operation. At 30 days after surgery, 261 (11.2%) patients had experienced the primary end point of massive bleeding. There was a nonsignificant trend towards lower rates of bleeding among patients in the aprotinin group than in those receiving the other two study drugs (9.5% vs 12.1%; relative risk 0.79, 95% CI 0.59–1.05). Aprotinin was associated with a relative increase in 30-day mortality of >50% (absolute increase 2.1%) compared with the lysine analogs (relative risk 1.53; 95% CI 1.06–2.22), however, and the trial was stopped early.

The authors conclude that, although aprotinin might prevent major bleeding, the unacceptably high mortality risk associated with this agent prohibits its use in patients undergoing high-risk cardiac surgery.