Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients

Abstract

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 (nϭ15 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; PϽ0.001). The incidence of ARF directly and significantly increased with increasing transfusions of PRBC (PϽ0.001). Risk-adjusted analysis without transfused PRBC in the model suggests that aprotinin significantly impacts ARF (Pϭ0.008; ORϭ1.5). However, further risk adjustment with the addition of the highly significant transfused PRBC variable (PϽ0.0001; ORϭ1.23/transfused PRBC) to the model attenuates the purported independent affect of aprotinin (Pϭ0.231) 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.

Resultados de una encuesta nacional sobre hábito transfusional en unidades de cuidados intensivos

“…Es destacable la escasa presencia de dispositivos recuperadores de sangre, con utilización esporádica de aprotinina, eritropoyetina (< 5 casos/año) y factor VII activado. Es posible que estos datos hayan cambiado, fundamentalmente hacia su aumento, en los últimos años [20][21][22][23][24][25][26] .…”

Acute Kidney Injury Following Cardiac Surgery: Prevention, Diagnosis, and Management

“…(Mangano, Tudor et al 2006) This finding has since been supported and opposed by similar large observational studies. (Furnary, Wu et al 2007;Dietrich, Busley et al 2008;Shaw, Stafford-Smith et al 2008) More recently, an increased 30-day mortality in the aprotinin arm of the BART study (Blood Conservation Using Antifibrinolytics in a Randomized Trial) prompted the Food and Drug Administration to suspend marketing of the drug. (Fergusson, Hébert et al 2008) …”

Letter by Landis et al Regarding Article “Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients”

“…We read with interest the article by Furnary and colleagues 1 showing that aprotinin does not increase the risk of renal failure in cardiac surgery patients, casting further doubt on the conclusions of a study by Mangano et al 2 The article by Furnary et al demonstrates that risk for kidney failure is solely attributed to the greater numerical need for packed red blood cell transfusion in high-risk patients selected by physicians to receive aprotinin, and that packed red blood cells carry with them a highly significant independent risk of causing renal failure. These conclusions echo the concerns expressed in the aftermath of the article by Mangano et al, 3 that such an important confounding factor had not been corrected for in multivariate analysis.…”