The efficacy and safety of aprotinin use in cardiac surgery.

BACKGROUND

The serine protease inhibitor aprotinin has received much attention in cardiac surgical practice as a pharmacologic intervention to improve the hemostatic derangement associated with cardiopulmonary bypass. This review highlights the major studies undertaken to investigate the efficacy and safety of aprotinin use in both primary and repeat coronary artery bypass graft surgical procedures.

METHODS

There have been at least 45 controlled studies in more than 7,000 patients in a variety of patient populations. These have ranged from primary coronary artery bypass graft and valve operations to complex reoperation procedures, including aortic arch reconstructions and thoracic organ transplantation. The recently completed International Multicenter Graft Patency Experience trial, the largest study to date, involved 870 patients at 13 international sites. The study examined the effects of aprotinin on graft patency, incidence of myocardial infarction, and blood loss in patients undergoing primary coronary artery bypass graft operations with cardiopulmonary bypass.

RESULTS

Twenty-one studies in approximately 5,000 patients undergoing primary coronary artery bypass graft or valve operations reported 33% to 66% reduction in blood loss with full-dose aprotinin therapy; 15 of the same studies reported significant reductions in transfusion requirements, ranging from 31% to 85%. The recently completed International Multicenter Graft Patency Experience study observed a significant reduction in thoracic-drainage volume of 43% (p < 0.0001) and a 49% (p < 0.001) reduction in the requirement for allogeneic blood transfusions. Aprotinin did not affect the occurrence of definite myocardial infarction (aprotinin, 2.9% versus placebo, 3.8%) or mortality (aprotinin, 1.4% versus placebo, 1.6%). There was no observed difference in the patency of internal mammary artery bypass grafts from all study sites in aprotinin- versus placebo-treated patients (aprotinin, 98.2% versus placebo, 98.0%).

CONCLUSIONS

Given the risks and costs associated with excessive bleeding and transfusions and the limited supply of banked blood, aprotinin represents an important and safe approach to blood conservation.