Aprotinin versus lysine analogues: the debate continues

The decision to use any pharmacologic intervention inevitably rests on balancing the efficacy and safety of the intervention. The advent of the acquired immunodeficiency syndrome epidemic greatly increased awareness of transfusion-related illnesses and focused attention on methods to prevent the need for blood and blood products. This has led, especially in the last decade, to increased use of drugs to help reduce perioperative bleeding. This chapter focuses on the lysine analogues and aprotinin as the serine protease inhibitor currently available in clinical practice. Both groups of compounds have recently shown promise in reducing surgical bleeding. However, the reader will notice that none of these agents are new; they have all been available for more than 30 years. What is new is their use in preventing bleeding. We therefore have considerable knowledge regarding the safety of these compounds. The first part of this review will compare the actions of these two types of agents on the processes related to thrombosis, hemostasis, and fibrinolysis. This is followed by a comparison of the efficacy of each intervention and any dose-response relationship. This section highlights the reported reduction in postoperative bleeding with both classes of agent. There is, however, no obvious or consistent reduction in the transfusion of blood and blood products in patients given lysine analogues. In contrast, there is a consistent reduction in the need for blood transfusions in patients given aprotinin therapy. The next major section will discuss the evidence to suggest that these drugs may, because of their known effects on the processes related to inflammation, hemostasis, and cellular repair, contribute to an improvement or worsening of outcome after cardiac operations. In particular, this section focuses on the antiinflammatory actions and modifications in vascular tone associated with aprotinin therapy. These effects may be related to improved outcome in patients by reducing the incidence of permanent neurologic deficit or stroke after heart operations, as well as inhibiting pulmonary vascular hyperreactivity and hypertension in susceptible individuals. Finally, this brief review discusses the safety issues that have been raised in regard to each of these classes of agents, specifically problems associated with abnormal renal function, hypersensitivity reactions, and thrombotic complications.