Cost-Benefit and Efficacy of Aprotinin Compared with ε-Aminocaproic Acid in Patients Having Repeated Cardiac Operations

Authors:
  • JSJonathan G. Sorohan
    Jonathan G. Sorohan
  • MGMiguel L. Gurevich
    Miguel L. Gurevich
  • PKPaul E. Kazanjian
    Paul E. Kazanjian
  • RLRoberto R. Levy
    Roberto R. Levy
  • ABAlberto V. Barbera
    Alberto V. Barbera
  • WWWilliam D. White
    William D. White
  • TSThomas F. Slaughter
    Thomas F. Slaughter
  • RSRobert N. Sladen
    Robert N. Sladen
  • PSPeter K. Smith
    Peter K. Smith
  • MNMark F. Newman
    Mark F. Newman
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Abstract
Background: Aprotinin and epsilon-aminocaproic acid are routinely used to reduce bleeding during cardiac surgery. The marked difference in average wholesale cost between these two drug therapies (aprotinin, $1,080 vs. epsilon-aminocaproic acid, $11) has generated significant controversy regarding their relative efficacies and costs. Methods: In a multicenter, randomized, prospective, blinded trial, patients having repeated cardiac surgery received either a high-dose regimen of aprotinin (total dose, 6 x 10(6) kallikrein inactivator units) or epsilon-aminocaproic acid (total dose, 270 mg/kg). Results: Two hundred four patients were studied. Overall (data are median [25th-75th percentiles]), aprotinin-treated patients had less postoperative thoracic drainage (511 ml [383-805 ml] vs. 655 ml [464-1,045 ml]; P = 0.016) and received fewer platelet transfusions (0 [range, 0-1] vs. 1 [range, 0-2]; P = 0.036). The surgical field was more likely to be considered free of bleeding in aprotinin-treated patients (44% vs. 26%; P = 0.012). No differences, however, were seen in allogeneic erythrocyte transfusions or in the time required for chest closure. Overall, direct and indirect bleeding-related costs were greater in aprotinin- than in epsilon-aminocaproic acid-treated patients ($1,813 [$1,476-2,605] vs. $1,088 [range, $511-2,057]; P = 0.0001). This difference in cost per case varied in magnitude among sites but not in direction. Conclusions: Aprotinin was more effective than epsilon-aminocaproic acid at decreasing bleeding and platelet transfusions. Epsilon-aminocaproic acid, however, was the more cost-effective therapy over a broad range of estimates for bleeding-related costs in patients undergoing repeated cardiac surgery. A cost-benefit analysis using the lower cost of half-dose aprotinin ($540) still resulted in a significant cost advantage using epsilon-aminocaproic therapy (P = 0.022).