The effect of aprotinin on outcome after coronary-artery bypass grafting

N Engl J Med. 2008 Feb 21;358(8):784-93. doi: 10.1056/NEJMoa0707768.


Background: Aprotinin has recently been associated with adverse outcomes in patients undergoing cardiac surgery. We reviewed our experience with this agent in patients undergoing cardiac surgery at Duke University Medical Center.

Methods: We retrieved data on 10,275 consecutive patients undergoing surgical coronary revascularization at Duke between January 1, 1996, and December 31, 2005. We fit data to a logistic-regression model predicting each patient's likelihood of receiving aprotinin on the basis of preoperative characteristics and to models predicting long-term survival (up to 10 years) and decline in renal function, as measured by increases in serum creatinine levels.

Results: A total of 1343 patients (13.2%) received aprotinin, 6776 patients (66.8%) received aminocaproic acid, and 2029 patients (20.0%) received no antifibrinolytic therapy. All patients underwent coronary-artery bypass grafting, and 1181 patients (11.5%) underwent combined coronary-artery bypass grafting and valve surgery. In the risk-adjusted model, survival was worse among patients treated with aprotinin, with a main-effects hazard ratio for death of 1.32 (95% confidence interval [CI], 1.12 to 1.55) for the comparison with patients receiving no antifibrinolytic therapy (P=0.003) and 1.27 (95% CI, 1.10 to 1.46) for the comparison with patients receiving aminocaproic acid (P=0.004). As compared with the use of aminocaproic acid or no antifibrinolytic agent, aprotinin use was also associated with a larger risk-adjusted increase in the serum creatinine level (P<0.001) but not with a greater risk-adjusted incidence of dialysis (P=0.56).

Conclusions: Patients who received aprotinin had a higher mortality rate and larger increases in serum creatinine levels than those who received aminocaproic acid or no antifibrinolytic agent.

MeSH terms

  • Aged
  • Aminocaproates / adverse effects
  • Aminocaproates / therapeutic use
  • Antifibrinolytic Agents / adverse effects*
  • Antifibrinolytic Agents / therapeutic use
  • Aprotinin / adverse effects*
  • Aprotinin / therapeutic use
  • Blood Loss, Surgical / prevention & control
  • Cohort Studies
  • Coronary Artery Bypass*
  • Coronary Disease / surgery
  • Creatinine / blood
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / drug effects
  • Kidney / physiology
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / therapy
  • Logistic Models
  • Middle Aged
  • Mortality*
  • Renal Dialysis
  • Retrospective Studies
  • Treatment Outcome


  • Aminocaproates
  • Antifibrinolytic Agents
  • Aprotinin
  • Creatinine