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J Thorac Cardiovasc Surg 1999;118:979
© 1999 Mosby, Inc.

LETTERS TO THE EDITOR

Drug therapy before coronary artery operations

William M. Weightman, MB, ChB, M. A. J. Newman, MD

Departments of Anesthesia and Cardiac Surgery
Sir Charles GairdnerHospital
Verdun St
Nedlands 6009, Australia

To the Editor:

We were greatly interested by the results of the IMAGE trial,Go 1 which suggests European patientsare more susceptible than US patients to aprotinin-induced vein graft occlusion.This has prompted us to inquire whether our patients have a European or USresponse to aprotinin.

We have used aprotinin in varying doses for patients undergoing redooperations or for those with recent aspirin ingestion. Table I describes ourmortality rate in consecutive patients undergoing coronary artery bypass graftingwith or without other procedures between 1993 and 1998; a dose-dependent increasein mortality is evident. However, the indications for aprotinin are also very important riskfactors for perioperative mortality. Thus it may not be too surprising thatpatients given aprotinin have a higher mortality rate. To clarify this, wehave further analyzed our data to take risk factors for mortality into account.


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  		Table I. Doseof aprotinin, number of patients, and in-hospital mortality rate for 1593consecutive patients undergoing coronary artery operations
 
The patients and model have been described in detail elsewhere.Go 2 Logistic regression was performedwith in-hospital mortality from any cause as the dependent factor and 22 independentfactors: age, sex, urgency of the operation, history of cardiac surgery, concurrentcardiac or cardiovascular procedures, left ventricular function, recent myocardialinfarct, left main coronary artery stenosis, chronic airways disease, cerebrovasculardisease, diabetes, hypertension, and other risk factors including preoperativecardioactive drug use. Stepwise regression was not used.

In this model we found the relative risk of mortality attributable toaprotinin to be 1.34 per million units of aprotinin with 95% confidence intervalsof 1.1 to 1.7 (P = .01 for relative risk =1). This indicates a risk-adjusted association between aprotinin and in-hospitalmortality.

In the jargon of evidence-based medicine, our data are "classIII evidence" and should not be considered conclusive. However, takenin conjunction with the IMAGE trial results, our data support the hypothesisthat in some circumstances aprotinin may have a deleterious effect on patientsundergoing coronary artery operations.

We do not understand why aprotinin appears to have adverse effects insome surgical units and not others. We use balanced salt solutions for veindistention, maintain kaolin-activated clotting times above 600 seconds, andnever administer our blood cardioplegic solution through vein grafts. Untilit becomes clear why the adverse effects of aprotinin appear to be site specific,we would suggest that aprotinin should be used with caution in coronary arteryoperations.

12/8/101197

References

  1. Alderman EL, Levy JH, Rich JB, Nili M,Vidne B, Schaff H, et al. Analyses of coronary graft patency after aprotininuse: results from the International Multicenter Aprotinin Graft Patency Experience(IMAGE) trial. J Thorac Cardiovasc Surg 1998;16:716-30.
  2. Weightman WM, Gibbs NM, Sheminant MR, WhitfordEG, Mahon BD, Newman MAJ. Drug therapy before coronary artery surgery: nitratesare independent predictors of mortality and beta adrenergic blockers predictsurvival. Anesth Analg 1999;88:286-91.[Abstract/Free Full Text]




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