A comparison of aprotinin and lysine analogues in high-risk cardiac surgery

N Engl J Med. 2008 May 29;358(22):2319-31. doi: 10.1056/NEJMoa0802395. Epub 2008 May 14.


Background: Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences.

Methods: In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days.

Results: The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22).

Conclusions: Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminocaproates / adverse effects
  • Aminocaproates / therapeutic use*
  • Antifibrinolytic Agents / adverse effects
  • Antifibrinolytic Agents / therapeutic use*
  • Aprotinin / adverse effects
  • Aprotinin / therapeutic use*
  • Blood Transfusion / statistics & numerical data
  • Cardiac Surgical Procedures* / mortality
  • Double-Blind Method
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Length of Stay
  • Lysine / analogs & derivatives*
  • Male
  • Middle Aged
  • Postoperative Hemorrhage / epidemiology
  • Postoperative Hemorrhage / prevention & control*
  • Tranexamic Acid / adverse effects
  • Tranexamic Acid / therapeutic use*
  • Treatment Outcome


  • Aminocaproates
  • Antifibrinolytic Agents
  • Tranexamic Acid
  • Aprotinin
  • Lysine

Associated data

  • ISRCTN/ISRCTN15166455