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: M Klein, P R Keith, H P Dauben, H D Schulte, H Beckmann, G Mayer, O Elert, E Gams
• Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery (Eur J Cardiothorac Surg) Vol. 14 Issue 4 Pg. 360-6 (Oct 1998) ISSN: 1010-7940 [Print] Germany
• PMID: 9845139 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Fibrinolytic Agents
• Hemostatics
• Isoenzymes
• Placebos
• Thromboxanes
• Aprotinin
• Creatine Kinase
• Aspirin

Topics

• Aprotinin (administration & dosage, adverse effects, therapeutic use)
• Aspirin (administration & dosage, therapeutic use)
• Blood Loss, Surgical (prevention & control)
• Coronary Artery Bypass
• Creatine Kinase (blood)
• Double-Blind Method
• Electrocardiography
• Female
• Fibrinolytic Agents (administration & dosage, therapeutic use)
• Hemostatics (administration & dosage, adverse effects, therapeutic use)
• Humans
• Intraoperative Care
• Isoenzymes
• Male
• Middle Aged
• Multivariate Analysis
• Myocardial Infarction (etiology, prevention & control)
• Placebos
• Postoperative Hemorrhage (prevention & control)
• Prospective Studies
• Reproducibility of Results
• Risk Factors
• Thromboxanes (blood)