title: Aprotinin counterbalances an increased risk of peri-operative hemorrhage in CABG patients pre-treated with Aspirin.
abstract: OBJECTIVE
  As Aspirin (ASA) has proven efficacy in preventing patients with CAD from complications related to cardiovascular diseases, most patients scheduled for CABG are treated with ASA therapy. Consequently, impaired hemostasis is a problem in the management of CABG patients. Clinical studies have shown that Aprotinin can reduce bleeding and the use of blood products by 50% in patients both with and without pre-operative ASA therapy. Concerning the combined effect of peri-operative low-dose ASA therapy and intra-operative high-dose Aprotinin therapy, the gathering of additional and prospective data seemed to be necessary.
  
  
  METHODS
  We conducted a double-blind two-centre randomised three-arm study in patients with elective primary CABG surgery. Three groups have been tested, comprising 119 patients in total (group A: ASA + Aprotinin, group B: placebo + Aprotinin, group C: placebo + placebo) 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 administration (B vs. C; P = 0.009). The unexpected result of this study has been that the pre-treatment with ASA led to a further reduction of 18% (A vs. C; P < 0.0001). The difference between 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 levels of 1.8% in total (2/113), 2.6% (1/38) in group B and 3.2% (1/31 ) in group C. An additional blinded evaluation of ECG, enzyme levels and clinical status revealed 'definite, probable and possible' MIs of 5% in group A, compared 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 group to non-ASA pre-treatment, a strong trend towards a reduction in MI rate becomes obvious, from 15% to 5% in favour of the ASA pre-treatment (P = 0.08). Concerning other peri-operative complications, no statistical difference between the groups could be detected.
  
  
  CONCLUSIONS
  A reduction in post-operative blood loss in primary elective CABG surgery with intra-operative Aprotinin treatment could be confirmed. A low-dose ASA treatment combined with a high-dose aprotinin administration during surgery not only neutralized a potentially higher risk of bleeding, but did in fact reduce the post-operative blood loss. The protective effect of ASA on peri-operative MI has been evident through a reduction of MI rate in ASA treated patients.
authors.affiliation: Heinrich-Heine-University Duesseldorf, Department of Thoracic- and Cardiovascular Surgery, Germany. kleinmi@uni-duesseldorf.de
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.forename: P R
authors.initials: PR
authors.lastname: Keith
authors.forename: H P
authors.initials: HP
authors.lastname: Dauben
authors.forename: H D
authors.initials: HD
authors.lastname: Schulte
authors.forename: H
authors.initials: H
authors.lastname: Beckmann
authors.forename: G
authors.initials: G
authors.lastname: Mayer
authors.forename: O
authors.initials: O
authors.lastname: Elert
authors.forename: E
authors.initials: E
authors.lastname: Gams
mesh_terms: D007611:Aprotinin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001026:Coronary Artery Bypass; D003402:Creatine Kinase / Q000097:blood; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007430:Intraoperative Care; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D010919:Placebos; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D013931:Thromboxanes / Q000097:blood
chemical_list: D005343:Fibrinolytic Agents; D006490:Hemostatics; D007527:Isoenzymes; D010919:Placebos; D013931:Thromboxanes; D007611:Aprotinin; D003402:Creatine Kinase; D001241:Aspirin