Aprotinin does not increase the risk of renal failure in cardiac surgery patients

Background - Aprotinin is frequently used in high-risk cardiac surgery patients to decrease bleeding complications and transfusions of packed red blood cells (PRBC). Transfusions of PRBC are known to directly increase the risk of new onset postoperative renal failure (ARF) in cardiac surgery patients. A recent highly publicized report implicated aprotinin as an independent causal factor for postoperative renal failure, but ignored the potential confounding affect of numerical PRBC data on ARF. We sought to investigate that claim with an analysis that included all perioperative risk factors for renal failure, including PRBC transfusion data. Methods and Results - Prospectively collected patient data from 12 centers contributing to the Merged Cardiac Registry, an international multicenter cardiac surgery database, operated on between January 2000 and February 2006 were retrospectively analyzed. A previously published risk model for ARF incorporating 12 variables was used to calculate a baseline ARF risk score for each patient in whom those variables were available (n = 15 174). After adding transfused PRBC data 11 198 patients remained for risk-adjusted assessment of ARF in relation to aprotinin use. Risk-adjusted multivariable analyses were carried out with, and without, consideration of transfused PRBC. Aprotinin was used in 24.6% (2757/11 198). The overall incidence of ARF was 1.6% (180/11 198) and was higher in the aprotinin subset (2.6%, 72/2757 versus 1.3%, 108/8441; P < 0.001). The incidence of ARF directly and significantly increased with increasing transfusions of PRBC (P < 0.001). Risk-adjusted analysis without transfused PRBC in the model suggests that aprotinin significantly impacts ARF (P = 0.008; OR = 1.5). However, further risk adjustment with the addition of the highly significant transfused PRBC variable (P < 0.0001; OR = 1.23/transfused PRBC) to the model attenuates the purported independent affect of aprotinin (P = 0.231) on ARF. Conclusions - The increase in renal failure seen in patients who were administered aprotinin was directly related to increased number of transfusions in that high-risk patient population. Aprotinin use does not independently increase the risk of renal failure in cardiac surgery patients.