Interact CardioVasc Thorac Surg 2009;9:101. doi:10.1510/icvts.2008.198325A
© 2009 European Association of Cardio-Thoracic Surgery
eComment: A comparison of the safety of aprotinin and tranexamic acid in cardiac surgery
Ioanna Koniari,
Efstratios Apostolakis and
Mandellou Martha
Department of Cardiothoracic Surgery, University Hospital of Patras, 22500 Rion Patras, Greece
Aprotinin increases mortality as compared with tranexamic acid in cardiac surgery: a meta-analysis of randomized head-to-head trials
It appears that meta-analyses agree that aprotinin increases the risk of death compared to lysine analogues, as you demonstrate in your review [1]. However, this conclusion is not as clear if we consider the clinical events that might cause an increase in the risk of death. Although there was an increase in cardiac death among patients who received aprotinin in the BART study, there was no increase in myocardial infarction, stroke or renal failure either in this trial or in the meta-analyses of Henry et al. [2]. The use of tranexamic acid appeared to reduce mortality; however, this effect was not statistically significant. As a consequence, the increased relative risk of death seen in the indirect comparison of aprotinin and tranexamic acid is because of lower mortality with the use of tranexamic acid, rather than an adverse effect of aprotinin [2].
Notably, Dietrich et al. [3], in a prospective, randomized, double-blind study included 220 patients undergoing primary coronary artery revascularization (CABG) or aortic valve replacement (AVR) demonstrated that: a) in the aprotinin group 47% of patients received allogeneic blood during the hospital stay as compared to 61% in the tranexamic acid group (P=0.036); b) aprotinin conferred a 23% reduction in allogeneic transfusion risk; c) moreover, the heparin requirement was reduced: 19% of the patients in the aprotinin group and 45% in the tranexamic acid group received at least one additional bolus heparin during cardiopulmonary bypass (P<0.001); d) troponin T levels postoperatively and on postoperative day 1 were significantly higher in the tranexamic acid group (P=0.017). Finally, no differences in renal, cardiac, or mortality outcomes were observed. In conclusion, concerning the rate of transfusion of red blood cells, tranexamic acid was slightly inferior in patients undergoing CABG, but there was no difference in patients receiving AVR.
On the other hand, Martin et al. [4], demonstrated that administration of aprotinin should be avoided in coronary artery bypass graft and high-risk patients, whereas administration of tranexamic acid is not recommended in valve surgery analyzing the incidence of acute myocardial infarction, atrial fibrillation or renal dysfunction/failure in corresponding patients.
Finally, Later et al. [5] indicated that aprotinin is the most effective antifibrinolytic agent in patients with normal renal function scheduled for low or intermediate risk cardiac surgery. Especially, aprotinin was about twice as effective as tranexamic acid in reducing total postoperative blood loss (estimated median difference 155 ml, P<0.001). Accordingly, aprotinin reduced packed red blood cell transfusions more than tranexamic acid, although the difference did not reach statistical significance. Only aprotinin significantly reduced the proportion of transfused patients when compared with placebo (mean difference –20.9%, P=0.013), and only aprotinin completely abolished bleeding-related re-explorations (mean difference 6.8%, P=0.004). Neither antifibrinolytic agent increased the incidence of mortality (mean difference tranexamic acid –0.4%, P=0.79, mean difference aprotinin –1.3%, P=0.62) compared with placebo.
In conclusion, the choice of aprotinin or tranexamic acid should be based on the type and severity of cardiac surgery and existing co-morbidity.
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References
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- Takagi H, Manabe H, Kawai N, Goto S, Umemoto T. Aprotinin increases mortality as compared with tranexamic acid in cardiac surgery: a meta-analysis of randomized head-to-head trials. Interact CardioVasc Thorac Surg 2009;9:98–101.[Abstract/Free Full Text]
- Henry D, Carless P, Fergusson D, Laupacis A. The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. CMAJ 2009;180:183–193.[Abstract/Free Full Text]
- Dietrich W, Spannagl M, Boehm J, Hauner K, Braun S, Schuster T, Busley R. Tranexamic acid and aprotinin in primary cardiac operations: an analysis of 220 cardiac surgical patients treated with tranexamic acid or aprotinin. Anesth Analg 2008;107:1469–1478.[Abstract/Free Full Text]
- Martin K, Wiesner G, Breuer T, Lange R, Tassani P. The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients. Anesth Analg 2008;107:1783–1790.[Abstract/Free Full Text]
- Later AF, Maas JJ, Engbers FH, Versteegh MI, Bruggemans EF, Dion RA, Klautz RJ. Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a non-sponsored, double-blind, randomised, placebo-controlled trial. Eur J Cardiothorac Surg, doi: 10.1016/j.ejcts.2008.11.038.[CrossRef]
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Aprotinin increases mortality as compared with tranexamic acid in cardiac surgery: a meta-analysis of randomized head-to-head trials
- Hisato Takagi, Hideaki Manabe, Norikazu Kawai, Shin-nosuke Goto, and Takuya Umemoto
Interactive CardioVascular and Thoracic Surgery 2009 9: 98-101.
[Abstract]
[Full Text]
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