• DOI:10.1056/NEJMoa0802395
• Corpus ID: 20355363

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

@article{Fergusson2008ACO,
  title={A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.},
  author={Dean A. Fergusson and Paul Hebert and C. David Mazer and Stephen E. Fremes and Charles MacAdams and John M. Murkin and Kevin H. T. Teoh and Peter C. Duke and Ramiro Arellano and Morris A. Blajchman and Jean S. Bussi{\`e}res and Dany C{\^o}t{\'e} and Jacek M. Karski and Raymond J. Martineau and James A. Robblee and Marc Alan Rodger and George A. Wells and Jennifer J. Clinch and Roanda Pretorius},
  journal={The New England journal of medicine},
  year={2008},
  volume={358 22},
  pages={
          2319-31
        }
}

• D. Fergusson, P. Hebert, +16 authors R. Pretorius
• Published 29 May 2008
• Medicine
• The New England journal of medicine

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].).