(Circulation. 1995;92:2236-2244.)
© 1995 American Heart Association, Inc.
Articles |
A Multicenter, Double-Blind, Placebo-Controlled Trial of Aprotinin for Reducing Blood Loss and the Requirement for Donor-Blood Transfusion in Patients Undergoing Repeat Coronary Artery Bypass Grafting
From the Department of Anesthesiology, Emory University Hospital, Atlanta, Ga (J.H.L.); the Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Maywood, Ill (R.P.); the Section of Cardiovascular Surgery, Mayo Clinic, Rochester, Minn (H.V.S.); the Department of Anesthesiology, Hahnemann University, Philadelphia, Pa (J.C.H.); Virginia Heart Surgery Associates, Fairfax (R.A.); the Department of Anesthesiology, University of Washington Medical Center, Seattle (B.S.); the Division of Cardiothoracic Surgery, Cornell Medical Center, New York, NY (T.K.R.); the Department of Anesthesiology, University of Michigan Medical Center, Ann Arbor (J.M.); the Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC (P.S.); the Department of Surgery, Allegheny General Hospital, Pittsburgh, Pa. (R.E.C.); and Miles Inc Pharmaceutical Division, West Haven, Conn (A.N., S.L.B., R.K.).
Background Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery.
Methods and Results Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor–red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P=.001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6±0.2 U; low-dose aprotinin, 1.6±0.3 U; pump-prime-only, 2.5±0.3 U; and placebo, 3.4±0.5 U; P=.0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2±0.4 U; low-dose aprotinin, 3.4±0.9 U; pump-prime-only, 5.1±0.9 U; placebo, 10.3±1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI).
Conclusions This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.
Key Words: cardiopulmonary bypass • aprotinin • bleeding • fibrinolysis • surgery
This article has been cited by other articles:
 |
|
 |
|
  B.J. Evans, D.O. Haskard, J.R. Finch, I.R. Hambleton, R.C. Landis, and K.M. Taylor The inflammatory effect of cardiopulmonary bypass on leukocyte extravasation in vivo. J. Thorac. Cardiovasc. Surg., May 1, 2008; 135(5): 999 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Bittner, J. Lemke, M. Lange, A. Rastan, and F. W. Mohr The impact of aprotinin on blood loss and blood transfusion in off-pump coronary artery bypass grafting. Ann. Thorac. Surg., May 1, 2008; 85(5): 1662 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Levy, K. A. Tanaka, and J. M. Bailey Cardiac Surgical Pharmacology Card. Surg. Adult, January 1, 2008; 3(2008): 77 - 110. [Full Text]
|
|
|
|
|
|
G. V. Gonzalez-Stawinski and B. W. Lytle Coronary Artery Reoperations Card. Surg. Adult, January 1, 2008; 3(2008): 711 - 732. [Full Text]
|
|
|
|
|
|
C. L. Backer, A. M. Kelle, R. D. Stewart, S. C. Suresh, F. N. Ali, R. A. Cohn, R. Seshadri, and C. Mavroudis Aprotinin is safe in pediatric patients undergoing cardiac surgery. J. Thorac. Cardiovasc. Surg., December 1, 2007; 134(6): 1421 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. McEvoy, S. T. Reeves, J. G. Reves, and F. G. Spinale Aprotinin in Cardiac Surgery: A Review of Conventional and Novel Mechanisms of Action Anesth. Analg., October 1, 2007; 105(4): 949 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Furnary, Y. Wu, L. F. Hiratzka, G. L. Grunkemeier, and U. S. Page 3rd Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients Circulation, September 11, 2007; 116(11_suppl): I-127 - I-133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bakaeen, D. Rice, A. M. Correa, G. L. Walsh, A. A. Vaporciyan, J. B. Putnam, S. G. Swisher, J. A. Roth, J. Huh, D. Chu, et al. Use of Aprotinin in Extrapleural Pneumonectomy: Effect on Hemostasis and Incidence of Complications Ann. Thorac. Surg., September 1, 2007; 84(3): 982 - 986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Brown, N. J.O. Birkmeyer, and G. T. O'Connor Meta-Analysis Comparing the Effectiveness and Adverse Outcomes of Antifibrinolytic Agents in Cardiac Surgery Circulation, June 5, 2007; 115(22): 2801 - 2813. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Mannucci and M. Levi Prevention and Treatment of Major Blood Loss N. Engl. J. Med., May 31, 2007; 356(22): 2301 - 2311. [Full Text] [PDF]
|
|
|
|
|
|
The Society of Thoracic Surgeons Blood Conservatio, V. A. Ferraris, S. P. Ferraris, S. P. Saha, E. A. Hessel II, C. K. Haan, B. D. Royston, C. R. Bridges, R. S.D. Higgins, G. Despotis, et al. Perioperative Blood Transfusion and Blood Conservation in Cardiac Surgery: The Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists Clinical Practice Guideline Ann. Thorac. Surg., May 1, 2007; 83(5_Supplement): S27 - S86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ouattara, H. Bouzguenda, Y. Le Manach, P. Leger, A. Mercadier, P. Leprince, N. Bonnet, G. Montalescot, B. Riou, and P. Coriat Impact of aspirin with or without clopidogrel on postoperative bleeding and blood transfusion in coronary surgical patients treated prophylactically with a low-dose of aprotinin Eur. Heart J., April 12, 2007; (2007) ehm049v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Dietrich, R. Busley, and M. Kriner High-Dose Aprotinin in Cardiac Surgery: Is High-Dose High Enough?: An Analysis of 8281 Cardiac Surgical Patients Treated with Aprotinin Anesth. Analg., November 1, 2006; 103(5): 1074 - 1081. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Royston, J. H. Levy, J. Fitch, W. Dietrich, S. C. Body, J. M. Murkin, B. D. Spiess, and A. Nadel Full-Dose Aprotinin Use in Coronary Artery Bypass Graft Surgery: An Analysis of Perioperative Pharmacotherapy and Patient Outcomes Anesth. Analg., November 1, 2006; 103(5): 1082 - 1088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Hogue Jr, C. A. Palin, and J. E. Arrowsmith Cardiopulmonary bypass management and neurologic outcomes: an evidence-based appraisal of current practices. Anesth. Analg., July 1, 2006; 103(1): 21 - 37. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. S. Day, R. C. Landis, and K. M. Taylor Aprotinin and the protease-activated receptor 1 thrombin receptor: antithrombosis, inflammation, and stroke reduction. Seminars in Cardiothoracic and Vascular Anesthesia, June 1, 2006; 10(2): 132 - 142. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Vincentelli, B. Jude, and S. Belisle Antithrombotic therapy in cardiac surgery: [Traitement antithrombotique en chirurgie cardiaque]. Can J Anesth, June 1, 2006; 53(6_suppl): S89 - S102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R.S. Day, D. O. Haskard, K. M. Taylor, and R. C. Landis Effect of Aprotinin and Recombinant Variants on Platelet Protease-Activated Receptor 1 Activation Ann. Thorac. Surg., February 1, 2006; 81(2): 619 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. F. L. Almodovar, P. Lima, A. Canas, and M. Calleja Fatal anaphylactoid reaction after primary exposure to aprotinin Interactive CardioVascular and Thoracic Surgery, February 1, 2006; 5(1): 25 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Mangano, I. C. Tudor, C. Dietzel, and the Multicenter Study of Perioperative Ischemia Re The Risk Associated with Aprotinin in Cardiac Surgery N. Engl. J. Med., January 26, 2006; 354(4): 353 - 365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. O. Morgan Cost, quality, and risk: Measuring and stopping the hidden costs of coronary artery bypass graft surgery Am. J. Health Syst. Pharm., September 15, 2005; 62(18_Supplement_4): S2 - S5. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Engles Review and application of serine protease inhibition in coronary artery bypass graft surgery Am. J. Health Syst. Pharm., September 15, 2005; 62(18_Supplement_4): S9 - S14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Levy Overview of clinical efficacy and safety of pharmacologic strategies for blood conservation Am. J. Health Syst. Pharm., September 15, 2005; 62(18_Supplement_4): S15 - S19. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fergusson, K. C. Glass, B. Hutton, and S. Shapiro Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding? Clinical Trials, June 1, 2005; 2(3): 218 - 232. [Abstract] [PDF]
|
|
|
|
|
|
W. Beierlein, A. M. Scheule, W. Dietrich, and G. Ziemer Forty Years of Clinical Aprotinin Use: A Review of 124 Hypersensitivity Reactions Ann. Thorac. Surg., February 1, 2005; 79(2): 741 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Mahdy and N. R. Webster Perioperative systemic haemostatic agents Br. J. Anaesth., December 1, 2004; 93(6): 842 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Sedrakyan, T. Treasure, and J. A. Elefteriades Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: A systematic review and meta-analysis of randomized clinical trials J. Thorac. Cardiovasc. Surg., September 1, 2004; 128(3): 442 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Smith, S. K. Datta, L. H. Muhlbaier, G. Samsa, A. Nadel, and J. Lipscomb Cost analysis of aprotinin for coronary artery bypass patients: analysis of the randomized trials Ann. Thorac. Surg., February 1, 2004; 77(2): 635 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Shore-Lesserson, D. L. Reich, and D. H. Adams Invited commentary Ann. Thorac. Surg., February 1, 2004; 77(2): 642 - 643. [Full Text] [PDF]
|
|
|
|
|
|
S. R. Williams, A. Y. Denault, M. Pellerin, and R. Martineau Vasopressin for treatment of shock following aprotinin administration: [Traitement a la vasopressine pour un choc suivant l'administration d'aprotinine] Can J Anesth, February 1, 2004; 51(2): 169 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vernon and G. M. Pfeifer Blood Management Strategies for Critical Care Patients Crit. Care Nurse, December 1, 2003; 23(6): 34 - 41. [Full Text] [PDF]
|
|
|
|
|
|
D. P. Taggart, V. Djapardy, M. Naik, and A. Davies A randomized trial of aprotinin (Trasylol) on blood loss, blood product requirement, and myocardial injury in total arterial grafting J. Thorac. Cardiovasc. Surg., October 1, 2003; 126(4): 1087 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Nussmeier, C. B. Probert, D. Hirsch, J. R. Cooper Jr., I. D. Gregoric, T. J. Myers, and O. H. Frazier Anesthetic Management for Implantation of the Jarvik 2000TM Left Ventricular Assist System Anesth. Analg., October 1, 2003; 97(4): 964 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Costello, C. L. Backer, A. de Hoyos, H. J. Binns, and C. Mavroudis Aprotinin reduces operative closure time and blood product use after pediatric bypass Ann. Thorac. Surg., April 1, 2003; 75(4): 1261 - 1266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Frumento, C. M.N. O'Malley, and E. Bennett-Guerrero Stroke after cardiac surgery: a retrospective analysis of the effect of aprotinin dosing regimens Ann. Thorac. Surg., February 1, 2003; 75(2): 479 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Levy Invited commentary Ann. Thorac. Surg., February 1, 2003; 75(2): 483 - 484. [Full Text] [PDF]
|
|
|
|
|
|
J. H. Levy and K. A. Tanaka Inflammatory response to cardiopulmonary bypass Ann. Thorac. Surg., February 1, 2003; 75(2): S715 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Bailey, K. A. Tanaka, and J. H. Levy Cardiac Surgical Pharmacology Card. Surg. Adult, January 1, 2003; 2(2003): 85 - 118. [Full Text]
|
|
|
|
|
|
B. W. Lytle Coronary Artery Reoperations Card. Surg. Adult, January 1, 2003; 2(2003): 659 - 679. [Full Text]
|
|
|
|
 |
|
 L. Englberger, P. Markart, F.S. Eckstein, F.F. Immer, P.A. Berdat, and T.P. Carrel Aprotinin reduces blood loss in off-pump coronary artery bypass (OPCAB) surgery Eur. J. Cardiothorac. Surg., October 1, 2002; 22(4): 545 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Tweddell, G. M. Hoffman, K. A. Mussatto, R. T. Fedderly, S. Berger, R. D. B. Jaquiss, N. S. Ghanayem, S. J. Frisbee, and S. B. Litwin Improved Survival of Patients Undergoing Palliation of Hypoplastic Left Heart Syndrome: Lessons Learned From 115 Consecutive Patients Circulation, September 24, 2002; 106(12_suppl_1): I-82 - I-89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Englberger, B. Kipfer, P. A. Berdat, U. E. Nydegger, and T. P. Carrel Aprotinin in coronary operation with cardiopulmonary bypass: does "low-dose" aprotinin inhibit the inflammatory response? Ann. Thorac. Surg., June 1, 2002; 73(6): 1897 - 1904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Murkin and R. Hall Best evidence in anesthetic practice: Prognosis: cognitive function at hospital discharge predicts long-term cognitive function after coronary artery bypass surgery Can J Anesth, May 1, 2002; 49(5): 497 - 499. [Full Text] [PDF]
|
|
|
|
|
|
I. Q. Molenaar, R. J. Porte, M. G. Fitzsimons, and R. A. Peterfreund Aprotinin and Thromboembolism in Liver Transplantation: Is There Really a Causal Effect? * Response Anesth. Analg., May 1, 2002; 94(5): 1367 - 1368. [Full Text] [PDF]
|
|
|
|
|
|
G. A. Nuttall, D. N. Fass, L. J. Oyen, W. C. Oliver Jr., and M. H. Ereth A Study of a Weight-Adjusted Aprotinin Dosing Schedule During Cardiac Surgery Anesth. Analg., February 1, 2002; 94(2): 283 - 289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Murkin, J. Maurer, and S. Niemcryk Full dose aprotinin administration is associated with a significant decrease in perioperative stroke in patients undergoing elective cardiac surgery: a meta-analysis Ann. Thorac. Surg., January 1, 2002; 73(1): S374 - 374. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Murkin Adverse Central Nervous System Outcomes After Cardiopulmonary Bypass: A Beneficial Effect of Aprotinin? Seminars in Cardiothoracic and Vascular Anesthesia, November 1, 2001; 5(4): 282 - 285. [Abstract] [PDF]
|
|
|
|
|
|
J. H. Levy Pharmacologic preservation of the hemostatic system during cardiac surgery Ann. Thorac. Surg., November 1, 2001; 72(5): S1814 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Despotis, M. S. Avidan, and C. W. Hogue Jr Mechanisms and attenuation of hemostatic activation during extracorporeal circulation Ann. Thorac. Surg., November 1, 2001; 72(5): S1821 - 1831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Murkin Attenuation of neurologic injury during cardiac surgery Ann. Thorac. Surg., November 1, 2001; 72(5): S1838 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Mora Mangano, M. J. Neville, P. H. Hsu, I. Mignea, J. King, and D. C. Miller Aprotinin, Blood Loss, and Renal Dysfunction in Deep Hypothermic Circulatory Arrest Circulation, September 18, 2001; 104(90001): I-276 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Hennein Inflammation After Cardiopulmonary Bypass: Therapy for the Postpump Syndrome Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2001; 5(3): 236 - 255. [Abstract] [PDF]
|
|
|
|
|
|
J. Tatoulis, B. F. Buxton, and J. A. Fuller The radial artery in coronary re-operations Eur. J. Cardiothorac. Surg., March 1, 2001; 19(3): 266 - 273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Gott Leukodepletion and aprotinin improve clinical outcome after extracorporeal circulation Perfusion, January 1, 2001; 16(1_suppl): 5 - 9. [Abstract] [PDF]
|
|
|
|
|
|
D. M. McMullan, E. A.K. Beyer, I. Gregoric, B. Radovancevic, and O.H. Frazier Left ventricular reduction in a Jehovah's Witness Ann. Thorac. Surg., September 1, 2000; 70(3): 958 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Levy Platelet inhibitors and bleeding in cardiac surgical patients Ann. Thorac. Surg., August 1, 2000; 70(2): S9 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Beath, G. A. Nuttall, D. N. Fass, W. C. Oliver Jr., M. H. Ereth, and L. J. Oyen Plasma Aprotinin Concentrations During Cardiac Surgery: Full- Versus Half-Dose Regimens Anesth. Analg., August 1, 2000; 91(2): 257 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. H. Edmunds Jr The quill passes Ann. Thorac. Surg., July 1, 2000; 70(1): 1 - 2. [Full Text] [PDF]
|
|