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J Thorac Cardiovasc Surg 1999;118:979-980
© 1999 Mosby, Inc.

LETTERS TO THE EDITOR

Drug therapy before coronary artery operations

For the IMAGE Investigators
Division of Cardiovascular Medicine
StanfordUniversity School of Medicine
Falk Cardiovascular Research Center
CV-261,300 Pasteur Dr
Stanford CA 94305-5406

Reply to the Editor:

The letter by Weightman and Newman suggests a dose-dependant mortalityfor aprotinin doses ranging from 0 to 4,000,000 KIU (see their Table I). In the IMAGE study (J Thorac Cardiovasc Surg 1998;116:716-30),the average dose in aprotinin-treated patients was 5,550,000 KIU (n = 436).This total includes the 2,000,000 KIU loading dose, 2,000,000 KIU into thecardiopulmonary bypass circuit prime, plus 1,570,000 KIU by continuous infusionat a prescribed rate of 500,000 KIU per hour. IMAGE study results showed thatthis administration regimen for aprotinin had no effect on mortality (placebo,1.6%; aprotinin, 1.4%). In the IMAGE study, 7 hospital deaths occurred in434 placebo-treated patients (1.6%). This is similar to the 1.8% hospitalmortality reported for non-aprotinin treated patients by Weightman and Newman.However, aprotinin-treated patients in the IMAGE study had a substantiallylower hospital mortality than those patients treated with a comparable dose(4,000,000 KIU) in Weightman and Newman’s letter: 1.4% comparedwith 11.5%.

Weightman and Newman report that of 754 patients receiving aprotinin,93% received less than 4,000,000 KIU of aprotinin (see their Table I). Their reporting of the total dose makes unclear the administrationregimen (ie, pump only, half dose, or full dose, as in the IMAGE study) andtiming (from the beginning of the operation, as recommended, or, perhaps,after loss of hemostasis). Furthermore, and with the exception of pump-onlyadministration, aprotinin is typically administered as a constant infusionper hour. In the simplest scenario (no pump or loading dose), any differencesin the amount of aprotinin administered would result wholly from the lengthof the operation.

The variables that separated European from US patients in the IMAGEstudy were primarily related to adverse angiographic characteristics of therecipient vessels in addition to female sex, older age, prior aspirin use,and abnormal left ventricular ejection fraction. The only predictor variablesin the IMAGE study for which there are data in Weightman and Newman’spatient population (Anesth Analg 1999;88:286-91) are age, sex, and aspirinuse. Their patients were older than those in the IMAGE study (63.8 years comparedwith 61.6 years at US sites and 62.0 years at Danish and Israeli sites), hada higher proportion of women (20.5% compared with 9.4% at US sites and 14.3%at Danish and Israeli sites), and a higher proportion of aspirin users (58.8%compared with 42.8% at US sites and 26.1% at Danish and Israeli sites). Inthe IMAGE study, aspirin use was associated with a lower risk of graft occlusion,whereas the other 2 variables, sex and age, were consistent with patientshaving a higher risk for vein graft occlusion. Comparative data on Weightmanand Newman’s patient characteristics are too limited to determine whetherresponses are more similar to those observed in our European or US patientpopulations. It is also unclear whether Weightman and Newman’s dataare prospective or retrospective.

These differences suggest that patients in Weightman and Newman’spopulation—and particularly those receiving aprotinin—had a moreadverse patient profile than either US or European patients in the IMAGE studyor there were other technical differences in the surgical procedures. Thusinferences should not be made from a nonrandomized study, particularly onewith apparent treatment biases.

12/8/101196

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				J. V. Manchio, J. Gu, L. Romar, J. Brown, J. Gammie, R. N. Pierson III, B. Griffith, and R. S. Poston Disruption of Graft Endothelium Correlates With Early Failure After Off-Pump Coronary Artery Bypass Surgery Ann. Thorac. Surg., June 1, 2005; 79(6): 1991 - 1998. [Abstract] [Full Text] [PDF]

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