BACKGROUND: Because of recent concerns about the safety of aprotinin, we updated our 2007 Cochrane review that compared the relative benefits and risks of aprotinin and the lysine analogues tranexamic acid and epsilon aminocaproic acid. METHODS: We searched electronic databases, including CENTRAL, MEDLINE, EMBASE, Google and Google Scholar for trials of antifibrinolytic drugs used in adults scheduled for cardiac surgery. Searches were updated to January 2008. By comparing aprotinin and the 2 lysine analogues to control, we derived indirect head-to-head comparisons of aprotinin to the other drugs. We derived direct estimates of risks and benefits by pooling estimates from head-to-head trials of aprotinin and tranexamic acid or epsilon aminocaproic acid. RESULTS: For indirect estimates, we identified 49 trials involving 182 deaths among 7439 participants. The summary relative risk (RR) for death with aprotinin versus placebo was 0.93 (95% confidence interval [CI] 0.69-1.25). In the 19 trials that included tranexamic acid, there were 24 deaths among 1802 participants. The summary RR was 0.55 (95% CI 0.24-1.25). From the risk estimates derived for individual drugs, we calculated an indirect summary RR of death with use of aprotinin versus tranexamic acid of 1.69 (95% CI 0.70-4.10). To calculate direct estimates of death for aprotinin versus tranexamic acid, we identified 13 trials with 107 deaths among 3537 participants. The summary RR was 1.43 (95% CI 0.98-2.08). Among the 1840 participants, the calculated estimates of death for aprotinin compared directly to epsilon aminocaproic acid was 1.49 (95% CI 0.98-2.28). We found no evidence of an increased risk of myocardial infarction with use of aprotinin compared with the lysine analogues in either direct or indirect analyses. Compared with placebo or no treatment, all 3 drugs were effective in reducing the need for red blood cell transfusion. The RR of transfusion with use of aprotinin was 0.66 (95% CI 0.61-0.72). The RR of transfusion was 0.70 (95% CI 0.61-0.80) for tranexamic acid, and it was 0.75 (95% CI 0.58-0.96) for use of epsilon aminocaproic acid. Aprotinin was also effective in reducing the need for re-operation because of bleeding (RR 0.48, 95% CI 0.34-0.67). INTERPRETATION: The risk of death tended to be consistently higher with use of aprotinin than with use of lysine analogues. Aprotinin had no clear advantages to offset these harms. Either tranexamic acid or epsilon aminocaproic acid should be recommended to prevent bleeding after cardiac surgery.
BACKGROUND: Because of recent concerns about the safety of aprotinin, we updated our 2007 Cochrane review that compared the relative benefits and risks of aprotinin and the lysine analogues tranexamic acid and epsilon aminocaproic acid. METHODS: We searched electronic databases, including CENTRAL, MEDLINE, EMBASE, Google and Google Scholar for trials of antifibrinolytic drugs used in adults scheduled for cardiac surgery. Searches were updated to January 2008. By comparing aprotinin and the 2 lysine analogues to control, we derived indirect head-to-head comparisons of aprotinin to the other drugs. We derived direct estimates of risks and benefits by pooling estimates from head-to-head trials of aprotinin and tranexamic acid or epsilon aminocaproic acid. RESULTS: For indirect estimates, we identified 49 trials involving 182 deaths among 7439 participants. The summary relative risk (RR) for death with aprotinin versus placebo was 0.93 (95% confidence interval [CI] 0.69-1.25). In the 19 trials that included tranexamic acid, there were 24 deaths among 1802 participants. The summary RR was 0.55 (95% CI 0.24-1.25). From the risk estimates derived for individual drugs, we calculated an indirect summary RR of death with use of aprotinin versus tranexamic acid of 1.69 (95% CI 0.70-4.10). To calculate direct estimates of death for aprotinin versus tranexamic acid, we identified 13 trials with 107 deaths among 3537 participants. The summary RR was 1.43 (95% CI 0.98-2.08). Among the 1840 participants, the calculated estimates of death for aprotinin compared directly to epsilon aminocaproic acid was 1.49 (95% CI 0.98-2.28). We found no evidence of an increased risk of myocardial infarction with use of aprotinin compared with the lysine analogues in either direct or indirect analyses. Compared with placebo or no treatment, all 3 drugs were effective in reducing the need for red blood cell transfusion. The RR of transfusion with use of aprotinin was 0.66 (95% CI 0.61-0.72). The RR of transfusion was 0.70 (95% CI 0.61-0.80) for tranexamic acid, and it was 0.75 (95% CI 0.58-0.96) for use of epsilon aminocaproic acid. Aprotinin was also effective in reducing the need for re-operation because of bleeding (RR 0.48, 95% CI 0.34-0.67). INTERPRETATION: The risk of death tended to be consistently higher with use of aprotinin than with use of lysine analogues. Aprotinin had no clear advantages to offset these harms. Either tranexamic acid or epsilon aminocaproic acid should be recommended to prevent bleeding after cardiac surgery.
Authors: Dean A Fergusson; Paul C Hébert; C David Mazer; Stephen Fremes; Charles MacAdams; John M Murkin; Kevin Teoh; Peter C Duke; Ramiro Arellano; Morris A Blajchman; Jean S Bussières; Dany Côté; Jacek Karski; Raymond Martineau; James A Robblee; Marc Rodger; George Wells; Jennifer Clinch; Roanda Pretorius Journal: N Engl J Med Date: 2008-05-14 Impact factor: 91.245
Authors: Andrew D Shaw; Mark Stafford-Smith; William D White; Barbara Phillips-Bute; Madhav Swaminathan; Carmelo Milano; Ian J Welsby; Solomon Aronson; Joseph P Mathew; Eric D Peterson; Mark F Newman Journal: N Engl J Med Date: 2008-02-21 Impact factor: 91.245
Authors: Dennis T Mangano; Yinghui Miao; Alain Vuylsteke; Iulia C Tudor; Rajiv Juneja; Daniela Filipescu; Andreas Hoeft; Manuel L Fontes; Zak Hillel; Elisabeth Ott; Tatiana Titov; Cynthia Dietzel; Jack Levin Journal: JAMA Date: 2007-02-07 Impact factor: 56.272
Authors: Santiago R Leal-Noval; Manuel Muñoz; Marisol Asuero; Enric Contreras; José A García-Erce; Juan V Llau; Victoria Moral; José A Páramo; Manuel Quintana Journal: Blood Transfus Date: 2013-06-17 Impact factor: 3.443
Authors: Sean van Diepen; Peter D Merrill; Michel Carrier; Jean-Claude Tardif; Mihai Podgoreanu; John H Alexander; Renato D Lopes Journal: J Thromb Thrombolysis Date: 2017-05 Impact factor: 2.300
Authors: Matthew E Kutcher; Michael W Cripps; Ryan C McCreery; Ian M Crane; Molly D Greenberg; Leslie M Cachola; Brittney J Redick; Mary F Nelson; Mitchell Jay Cohen Journal: J Trauma Acute Care Surg Date: 2012-07 Impact factor: 3.313
Authors: Pierre Tibi; R Scott McClure; Jiapeng Huang; Robert A Baker; David Fitzgerald; C David Mazer; Marc Stone; Danny Chu; Alfred H Stammers; Tim Dickinson; Linda Shore-Lesserson; Victor Ferraris; Scott Firestone; Kalie Kissoon; Susan Moffatt-Bruce Journal: J Extra Corpor Technol Date: 2021-06