The risk associated with aprotinin in cardiac surgery

N Engl J Med. 2006 Jan 26;354(4):353-65. doi: 10.1056/NEJMoa051379.


Background: The majority of patients undergoing surgical treatment for ST-elevation myocardial infarction receive antifibrinolytic therapy to limit blood loss. This approach appears counterintuitive to the accepted medical treatment of the same condition--namely, fibrinolysis to limit thrombosis. Despite this concern, no independent, large-scale safety assessment has been undertaken.

Methods: In this observational study involving 4374 patients undergoing revascularization, we prospectively assessed three agents (aprotinin [1295 patients], aminocaproic acid [883], and tranexamic acid [822]) as compared with no agent (1374 patients) with regard to serious outcomes by propensity and multivariable methods. (Although aprotinin is a serine protease inhibitor, here we use the term antifibrinolytic therapy to include all three agents.)

Results: In propensity-adjusted, multivariable logistic regression (C-index, 0.72), use of aprotinin was associated with a doubling in the risk of renal failure requiring dialysis among patients undergoing complex coronary-artery surgery (odds ratio, 2.59; 95 percent confidence interval, 1.36 to 4.95) or primary surgery (odds ratio, 2.34; 95 percent confidence interval, 1.27 to 4.31). Similarly, use of aprotinin in the latter group was associated with a 55 percent increase in the risk of myocardial infarction or heart failure (P<0.001) and a 181 percent increase in the risk of stroke or encephalopathy (P=0.001). Neither aminocaproic acid nor tranexamic acid was associated with an increased risk of renal, cardiac, or cerebral events. Adjustment according to propensity score for the use of any one of the three agents as compared with no agent yielded nearly identical findings. All the agents reduced blood loss.

Conclusions: The association between aprotinin and serious end-organ damage indicates that continued use is not prudent. In contrast, the less expensive generic medications aminocaproic acid and tranexamic acid are safe alternatives.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • 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
  • Cardiac Surgical Procedures*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / epidemiology
  • Cerebrovascular Disorders / chemically induced
  • Cerebrovascular Disorders / epidemiology
  • Female
  • Humans
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / epidemiology
  • Postoperative Hemorrhage / prevention & control
  • Prospective Studies
  • Renal Insufficiency / chemically induced*
  • Renal Insufficiency / epidemiology
  • Serine Proteinase Inhibitors / adverse effects*
  • Serine Proteinase Inhibitors / therapeutic use
  • Tranexamic Acid / adverse effects
  • Tranexamic Acid / therapeutic use


  • Aminocaproates
  • Antifibrinolytic Agents
  • Serine Proteinase Inhibitors
  • Tranexamic Acid
  • Aprotinin