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Previous Volume 358:2319-2331 May 29, 2008 Number 22 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Ray, W. A. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

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] .)

Source Information

From the Ottawa Health Research Institute (D.A.F., P.C.H., M.R., J.C., R.P.), the University of Ottawa (D.A.F., P.C.H., J.A.R., M.R., G.W.), and the University of Ottawa Heart Institute (J.A.R., G.W.) — all in Ottawa; the University of Toronto (C.D.M., S.F., J.K.), Keenan Center/Li Ka Shing Institute, St. Michael's Hospital (C.D.M.), the Sunnybrook Health Science Centre (S.F.), and Toronto General Hospital (J.K.) — all in Toronto; the University of Calgary, the Foothills Medical Centre, and the Libin Cardiovascular Institute of Alberta — all in Calgary, AB (C.M.); the University of Western Ontario, London, ON (J.M.M.); Hamilton Health Sciences Centre (K.T.), McMaster University (K.T., M.A.B.), and the Canadian Blood Services (M.A.B.) — all in Hamilton, ON; the University of Manitoba and the Health Sciences Centre, Winnipeg, MB (P.C.D.); Queen's University, Kingston, ON (R.A.); Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Laval, QC (J.S.B., D.C.); and Institut de Cardiologie de Montréal, Montreal (R.M.) — all in Canada.

Dr. Martineau is deceased.

This article (10.1056/NEJMoa0802395) was published at www.nejm.org on May 14, 2008.

Address reprint requests to Dr. Hébert at the Clinical Epidemiology Program, General Campus, Ottawa Health Research Institute, Box 208, 501 Smyth Rd., Ottawa, ON K1H 8L6, Canada, or at paul.hebert{at}cma.ca.

Full Text of this Article

Related Letters:

Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery
Porte R. J., Mallette S. V., Burroughs A. K., Myles P. S., Ray W. A., Stein C. M.
Extract | Full Text | PDF  
N Engl J Med 2008; 359:1181-1182, Sep 11, 2008. Correspondence

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