FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

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

This article has been cited by other articles:

• Takagi, H., Manabe, H., Kawai, N., Goto, S.-n., Umemoto, T. (2009). Aprotinin increases mortality as compared with tranexamic acid in cardiac surgery: a meta-analysis of randomized head-to-head trials. ICVTS 9: 98-101 [Abstract] [Full Text]  
• Greilich, P. E., Jessen, M. E., Satyanarayana, N., Whitten, C. W., Nuttall, G. A., Beckham, J. M., Wall, M. H., Butterworth, J. F. (2009). The Effect of Epsilon-Aminocaproic Acid and Aprotinin on Fibrinolysis and Blood Loss in Patients Undergoing Primary, Isolated Coronary Artery Bypass Surgery: A Randomized, Double-Blind, Placebo-Controlled, Noninferiority Trial. Anesth. Analg. 109: 15-24 [Abstract] [Full Text]  
• Manrique, A., Jooste, E. H., Kuch, B. A., Lichtenstein, S. E., Morell, V., Munoz, R., Ellis, D., Davis, P. J. (2009). The Association of Renal Dysfunction and the Use of Aprotinin in Patients Undergoing Congenital Cardiac Surgery Requiring Cardiopulmonary Bypass. Anesth. Analg. 109: 45-52 [Abstract] [Full Text]  
• Adams, D. H., Anyanwu, A. C., Chikwe, J., Filsoufi, F. (2009). The Year in Cardiovascular Surgery. J Am Coll Cardiol 53: 2389-2403 [Full Text]  
• Grunkemeier, G. L., Wu, Y., Furnary, A. P. (2009). What is the value of a p value?. Ann. Thorac. Surg. 87: 1337-1343 [Abstract] [Full Text]  
• Fowler, R. A., Adhikari, N. K. J., Scales, D. C., Lee, W. L., Rubenfeld, G. D. (2009). Update in Critical Care 2008. Am. J. Respir. Crit. Care Med. 179: 743-758 [Full Text]  
• Gist, R. S., Stafford, I. P., Leibowitz, A. B., Beilin, Y. (2009). Amniotic Fluid Embolism. Anesth. Analg. 108: 1599-1602 [Abstract] [Full Text]  
• Hlatky, M. A., Heidenreich, P. A. (2009). The Year in Epidemiology, Health Services Research, and Outcomes Research. J Am Coll Cardiol 53: 1459-1466 [Full Text]  
• Dunning, J. (2009). Reply to Katznelson et al. Tranexamic acid is safe with regard to vein graft patency. Eur. J. Cardiothorac. Surg. 35: 555-555 [Full Text]  
• Cook, A. M., Hessel, E. A. II (2009). Meta-Analysis of Statins for Aneurysmal Subarachnoid Hemorrhage Falls Short. Stroke 40: e79-e79 [Full Text]  
• Karkouti, K., Wijeysundera, D. N., Yau, T. M., Callum, J. L., Cheng, D. C., Crowther, M., Dupuis, J.-Y., Fremes, S. E., Kent, B., Laflamme, C., Lamy, A., Legare, J.-F., Mazer, C. D., McCluskey, S. A., Rubens, F. D., Sawchuk, C., Beattie, W. S. (2009). Acute Kidney Injury After Cardiac Surgery: Focus on Modifiable Risk Factors. Circulation 119: 495-502 [Abstract] [Full Text]  
• McIlroy, D. R., Myles, P. S., Phillips, L. E., Smith, J. A. (2009). Antifibrinolytics in cardiac surgical patients receiving aspirin: a systematic review and meta-analysis. Br J Anaesth 102: 168-178 [Abstract] [Full Text]  
• McEvoy, M. D., Sabbagh, M. J., Taylor, A. G., Zavadzkas, J. A., Koval, C. N., Stroud, R. E., Ford, R. L., McLean, J. E., Reeves, S. T., Mukherjee, R., Spinale, F. G. (2009). Aprotinin Modifies Left Ventricular Contractility and Cytokine Release After Ischemia-Reperfusion in a Dose-Dependent Manner in a Murine Model. Anesth. Analg. 108: 399-406 [Abstract] [Full Text]  
• Henry, D. MBChB, Carless, P. BHSc MMedS, Fergusson, D. PhD MHA, Laupacis, A. MD MSc (2009). The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. CMAJ 180: 183-193 [Abstract] [Full Text]  
• Breuer, T., Martin, K., Wilhelm, M., Wiesner, G., Schreiber, C., Hess, J., Lange, R., Tassani, P. (2009). The blood sparing effect and the safety of aprotinin compared to tranexamic acid in paediatric cardiac surgery. Eur. J. Cardiothorac. Surg. 35: 167-171 [Abstract] [Full Text]  
• Ngaage, D. L., Cale, A. R., Cowen, M. E., Griffin, S., Guvendik, L. (2008). Aprotinin in Primary Cardiac Surgery: Operative Outcome of Propensity Score-Matched Study. Ann. Thorac. Surg. 86: 1195-1202 [Abstract] [Full Text]  
• Brown, J. R. (2008). Invited Commentary. Ann. Thorac. Surg. 86: 1202-1203 [Full Text]  
• Porte, R. J., Mallette, S. V., Burroughs, A. K., Myles, P. S., Ray, W. A., Stein, C. M. (2008). Aprotinin and Lysine Analogues in High-Risk Cardiac Surgery. NEJM 359: 1181-1182 [Full Text]  
• Reeves, B. C., Murphy, G. J., Rogers, C. A., Culliford, L., Rizvi, S. I.A., Angelini, G. D. (2008). Response to Letter Regarding Article, "Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery". Circulation 117: e507-e507 [Full Text]  
• (2008). All you need to read in the other general journals. BMJ 336: 1271-1272 [Full Text]  
• Ray, W. A., Stein, C. M. (2008). The Aprotinin Story -- Is BART the Final Chapter?. NEJM 358: 2398-2400 [Full Text]