Mortality associated with aprotinin during 5 years following coronary artery bypass graft surgery.

CONTEXT: Acute safety concerns have been raised recently regarding certain hemorrhage-sparing medications commonly used in cardiac surgery. However, no comprehensive data exist regarding their associations with long-term mortality.

OBJECTIVE: To contrast long-term all-cause mortality in patients undergoing coronary artery bypass graft (CABG) surgery according to use of 2 lysine analog antifibrinolytics (aminocaproic acid and tranexamic acid), the serine protease inhibitor aprotinin, or no antibleeding agent.

DESIGN, SETTING, AND PARTICIPANTS: Observational study of mortality conducted between November 11, 1996, and December 7, 2006. Following index hospitalization (4374 patients; 69 medical centers), survival was prospectively assessed at 6 weeks, 6 months, and annually for 5 years after CABG surgery among 3876 patients enrolled in a 62-center international cohort study. The associations of survival with hemorrhage-sparing medications were compared using multivariable analyses including propensity adjustments.

MAIN OUTCOME MEASURE: Death (all-cause) over 5 years.

RESULTS: Aprotinin treatment (223 deaths among 1072 patients [20.8% 5-year mortality]) was associated with significantly increased mortality compared with control (128 deaths among 1009 patients [12.7%]; covariate adjusted hazard ratio for death, 1.48; 95% confidence interval, 1.19-1.85), whereas neither aminocaproic acid (132 deaths among 834 patients [15.8%]; adjusted hazard ratio for death, 1.03; 95% confidence interval, 0.80-1.33) nor tranexamic acid (65 deaths among 442 patients [14.7%]; adjusted hazard ratio for death, 1.07; 95% confidence interval, 0.80-1.45) was associated with increased mortality. In multivariable logistic regression, either with propensity adjustment or without, aprotinin was independently predictive of 5-year mortality (adjusted odds ratio with propensity adjustment, 1.48; 95% confidence interval, 1.13-1.93; P = .005) among patients with diverse risk profiles, as well as among those surviving their index hospitalization. Neither aminocaproic nor tranexamic acid was associated with increased risk of death.

CONCLUSIONS: These findings indicate that in addition to the previously reported acute renal and vascular safety concerns, aprotinin use is associated with an increased risk of long-term mortality following CABG surgery. Use of aprotinin among patients undergoing CABG surgery does not appear prudent because safer and less expensive alternatives (ie, aminocaproic acid and tranexamic acid) are available.