Impact of aprotinin on adverse clinical outcomes and mortality up to 12 years in a registry of 3,337 patients.

Background: Recent studies have suggested increased renal complications and long-term mortality with aprotinin use in coronary artery bypass grafting (CABG) patients. However, these studies have been criticized for including multiple centers and different dosing strategies. We analyzed prospectively collected registry data from a single center hospital utilizing a full-dose aprotinin regimen to evaluate if aprotinin was associated with increased mortality and adverse outcomes compared with Amicar.

Methods: Data were prospectively collected from 1994 to 2006 at a teaching hospital. Long-term mortality was collected from a Social Security database. To account for differences between aprotinin and Amicar-treated patients, a propensity score was generated and propensity-stratified multivariate model for mortality were performed.

Results: Compared with Amicar-treated patients (n = 1,830), aprotinin-treated patients (n = 1,507) were older, more often female, had lower creatinine clearance, and more baseline risk factors. Blood loss was lower in aprotinin-treated patients (median 715 mL vs 918 mL, p < 0.001). Postoperative renal failure was significantly higher in aprotinin patients (6.2% vs 2.7%, p < 0.001). At median 5.4-year follow-up (up to 12.2 years), aprotinin-treated patients had higher mortality versus Amicar-treated patients (Kaplan-Meier failure rates 43.5% vs 23.7% at 8 years, p < 0.0001). In a propensity-stratified model with multivariate adjustment, aprotinin remained associated with increased mortality (hazard ratio 1.62, 95% CI 1.39 to 1.90, p < 0.001). There was a stepwise relationship between weight-based aprotinin dose and mortality (p-trend < 0.001).

Conclusions: Among patients undergoing CABG in this registry, aprotinin use was associated with increased renal failure and higher mortality through 12 years in a propensity-stratified analysis. The increased mortality may be related to higher concentrations of aprotinin received.