Aprotinin - An update of its pharmacology and therapeutic use in open heart surgery and coronary artery bypass surgery

Cardiopulmonary bypass (CPB) is associated with defective haemostasis which results in bleeding and the requirement for allogenic blood product transf usions in many patients undergoing open heart surgery (OHS) and/or coronary artery bypass graft surgery (CABG) with CPB, Conservation of blood has bec ame a priority during surgery because of shortages of donor blood the risks associated with the use of allogenic blood products and the costs of these products. Aprotinin is a serine protease inhibitor isolated from bovine lung tissue w hich acts in a number of interrelated ways to provide an antifibrinolytic e ffect, inhibit contact activation, reduce platelet dysfunction and attenuat e the inflammatory response to CPB, It is used to reduce blood loss and tra nsfusion requirements in patients with a rink nf haemorrhage and has clear advantages over placebo or no treatment. High dose aprotinin significantly reduces postoperative blood loss compared with aminocaproic acid and desmopressin, and decreases transfusion require ments compared with desmopressin, Results are less consistent with tranexam ic acid: high dose aprotinin either reduces blood loss significantly more t han, or to an equi valent level to, tranexamic acid. A variety of other low er aprotinin dosage regimens consistently result in similar reductions in b lood loss to aminocaproic acid or tranexamic acid. Data from clinical trials indicate that aprotinin is generally well tolerat ed, and the adverse events seen are those expected in patients undergoing O HS and/or CABG with CPB, Hypersensitivity reactions occur in <0.1 to 0.6% o f patients receiving aprotinin for the first time. The results of original reports indicating that aprotinin therapy may increase myocardial infarctio n rates or mortality have not been supported by more recent studies specifi cally designed to investigate this outcome. However, a tendency to early ve in graft occlusion with aprotinin has been shown and care with anticoagulat ion and vessel grafts is required, No comparative tolerability data between aprotinin and the lysine analogues, aminocaproic acid and tranexamic acid, are available.