Aprotinin counterbalances an increased risk of peri-operative hemorrhage in CABG patients pre-treated with Aspirin

Objective: As Aspirin (ASA) has proven efficacy in preventing patients with CAD from complications related to cardiovascular diseases, most patients s cheduled for CABG are treated with ASA therapy. Consequently, impaired hemo stasis is a problem in the management of CABG patients. Clinical studies ha ve shown that Aprotinin can reduce bleeding and the use of blood products b y 50% in patients both with and without pre-operative ASA therapy. Concerni ng the combined effect of peri-operative low-dose ASA therapy and intra-ope rative high-dose Aprotinin therapy, the gathering of additional and prospec tive data seemed to be necessary. Methods: We conducted a double-blind two- centre randomised three-arm study in patients with elective primary CABG su rgery. Three groups have been tested, comprising 119 patients in total (gro up A: ASA + Aprotinin, group B: placebo + Aprotinin, group C: placebo + pla cebo) to investigate a possible reduction of bleeding in Aprotinin treated patients. For all patients, thromboxane levels were used to identify ASA or placebo treatment. Results: The post-operative blood loss is significantly reduced by 21% after Trasylol(R) administration (B vs. C; P = 0.009). The unexpected result of this study has been that the pre-treatment with ASA le d to a further reduction of 18% (A vs. C; P < 0.0001). The difference betwe en the two Aprotinin groups (A. and B) is significant (P = 0.01) in favour of ASA pre-treatment. Myocardial infarction (MI) had been diagnosed at leve ls of 1.8% in total (2/113), 2.6% (1/38) in group B and 3.2% (1/31) in grou p C. An additional blinded evaluation of EGG, enzyme levels and clinical st atus revealed 'definite, probable and possible' Mis of 5% in group A, compa red to 16% in group B and 13% in group C, thus providing no evidence for a higher risk of infarction by Aprotinin treatment. When comparing the ASA gr oup to non-ASA pre-treatment, a strong trend towards a reduction in MI rate becomes obvious, from 15% to 5% in favour of the BSA pre-treatment (P = 0. 08). Concerning other peri-operative complications, no statistical differen ce between the groups could be detected. Conclusions: A reduction in postop erative blood loss in primary elective CABG surgery with intra-operative Ap rotinin treatment could be confirmed. A low-dose ASA treatment combined wit h a high-dose aprotinin administration during surgery not only neutralized a potentially higher risk of bleeding, but did in fact reduce the post-oper ative blood loss. The protective effect of ASA on peri-operative MI has bee n evident through a reduction of MI rate in ASA treated patients. (C) 1998 Elsevier Science B.V. All rights reserved.