Cost-benefit and efficacy of aprotinin compared with epsilon-aminocaproic acid in patients having repeated cardiac operations: a randomized, blinded clinical trial.
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).
Bennett-Guerrero
E
E
The Mount Sinai Medical Center, New York, New York 10029-6574, USA. elliott_guerrero@smtplink.mssm.edu
Sorohan
J G
JG
Gurevich
M L
ML
Kazanjian
P E
PE
Levy
R R
RR
Barberá
A V
AV
White
W D
WD
Slaughter
T F
TF
Sladen
R N
RN
Smith
P K
PK
Newman
M F
MF
D000328:Adult; D000368:Aged; D015119:Aminocaproic Acid / Q000191:economics* / Q000627:therapeutic use*; D000933:Antifibrinolytic Agents / Q000191:economics / Q000627:therapeutic use*; D007611:Aprotinin / Q000191:economics* / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000191:economics*; D002315:Cardiopulmonary Bypass / Q000191:economics; D003362:Cost-Benefit Analysis; D004341:Drug Evaluation; D005260:Female; D006351:Heart Valves / Q000601:surgery; D006490:Hemostatics / Q000191:economics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012086:Reoperation; D016037:Single-Blind Method
D000933:Antifibrinolytic Agents; D006490:Hemostatics; D007611:Aprotinin; D015119:Aminocaproic Acid