Aprotinin and dipyridamole for the safe reduction of postoperative blood loss.
BACKGROUND
Aprotinin (APR) reduces postoperative blood loss but may induce thrombosis. Dipyridamole (DIP) limits platelet aggregation and may reduce the thrombotic complications associated with APR.


METHODS
To evaluate the safety and effectiveness of combined APR and DIP, we undertook a prospective randomized trial in patients undergoing cardiac operations. Patients were stratified according to risk for bleeding (low or high), and received either DIP with placebo (DIP group; n = 59) or DIP with APR (DIP + APR group; n = 56). Blood samples were obtained for the measurement of hematologic and biochemical parameters. Blood loss and transfusion requirements were documented postoperatively.


RESULTS
Postoperative blood loss and transfusion requirements were significantly lower in the DIP + APR group at 6, 12, and 24 hours after bypass (p < 0.01). No significant differences were found between groups in the incidence of perioperative mortality (DIP, 0%; DIP + APR, 3%), myocardial infarction (DIP, 0%; DIP + APR, 3%), stroke (DIP, 1%; DIP + APR, 1%), or potential thrombotic events (death, myocardial infarction, and stroke: DIP, 2%; DIP + APR, 5%). In addition, these rates did not differ from those of nonparticipating matched control patients.


CONCLUSIONS
Administration of both drugs simultaneously was more effective than DIP alone in reducing postoperative blood loss. A platelet inhibitor may be required to reduce the thrombotic complications associated with APR. Further studies evaluating graft patency and perioperative ischemia are necessary to confirm the potential benefits of the combination of a platelet inhibitor and APR.
Cohen
G
G
Division of Cardiovascular Surgery and the Centre for Cardiovascular Research, The Toronto Hospital and the University of Toronto, Ontario, Canada.
Ivanov
J
J
Weisel
R D
RD
Rao
V
V
Mohabeer
M K
MK
Mickle
D A
DA
D007611:Aprotinin / Q000008:administration & dosage*; D001777:Blood Coagulation / Q000187:drug effects; D004176:Dipyridamole / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D019918:Heart Valve Prosthesis Implantation; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011446:Prospective Studies; D016896:Treatment Outcome
D006490:Hemostatics; D010975:Platelet Aggregation Inhibitors; D004176:Dipyridamole; D007611:Aprotinin