A Cochrane review [Abstract] 1 included 252 studies with a total of over 25 000 subjects. Data from the head-to-head trials suggest an advantage of aprotinin over the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) in terms of reducing perioperative blood loss, but the differences were small. Compared to control, aprotinin reduced the probability of requiring red blood cell (RBC) transfusion by a relative 34% (RR 0.66, 95% CI 0.60 to 0.72; statistically significant heterogeneity I² = 89%). The RR for RBC transfusion with TXA was 0.61 (95% CI 0.53 to 0.70; statistically significant heterogeneity I² = 75%) and 0.81 (95% CI 0.67 to 0.99; statistically significant heterogeneity I² = 64%) with EACA. When the pooled estimates from the head-to-head trials of the two lysine analogues were combined and compared to aprotinin alone, aprotinin appeared more effective in reducing the need for RBC transfusion: RR 0.90 (95% CI 0.81 to 0.99; statistically significant heterogeneity I² = 59%).
Aprotinin reduced the need for re-operation due to bleeding: RR 0.46 (95% CI 0.34 to 0.62). This translates into an absolute risk reduction of 2% and a number needed-to-treat (NNT) of 50 (95% CI 33 to 100). Similar trend was seen with EACA (RR 0.32, 95% CI 0.11 to 0.99) but not TXA (RR 0.80, 95% CI 0.55 to 1.17). The blood transfusion data were heterogeneous and funnel plots indicate that trials of aprotinin and the lysine analogues may be subject to publication bias (favouring active treatment).
When compared with no treatment aprotinin did not increase the risk of myocardial infarction (RR 0.87, 95% CI 0.69 to 1.11), stroke (RR 0.82, 95% CI 0.44 to 1.52), renal dysfunction (RR 1.10, 95% CI 0.79 to 1.54) or overall mortality (RR 0.81, 95% CI 0.63 to 1.06). Similar trends were seen with the lysine analogues but data were sparse. These data conflict with the results of recently published non-randomised studies, which found increased risk of cardiovascular complications and death with aprotinin. There are concerns about the adequacy of reporting of uncommon events in the small clinical trials included in this review.
When aprotinin was compared directly with either, or both, of the two lysine analogues it resulted in a significant increase in the risk of death (RR 1.39, 95% CI 1.02, 1.89), and a non-significant increase in the risk of myocardial infarction (RR 1.11 95% CI 0.82, 1.50). Most of the data contributing to this added risk came from a single study - the BART trial (2008).
Comment: Aprotinin has been withdrawn from world markets because of safety concerns.
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