A multicenter, double-blind, placebo-controlled trial of aprotinin for reducing blood loss and the requirement for donor-blood transfusion in patients undergoing repeat coronary artery bypass grafting.
BACKGROUND
Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery.


RESULTS
Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor-red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall P = .001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6 +/- 0.2 U; low-dose aprotinin, 1.6 +/- 0.3 U; pump-prime-only, 2.5 +/- 0.3 U; and placebo, 3.4 +/- 0.5 U; P = .0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2 +/- 0.4 U; low-dose aprotinin, 3.4 +/- 0.9 U; pump-prime-only, 5.1 +/- 0.9 U; placebo, 10.3 +/- 1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI).


CONCLUSIONS
This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.
Levy
J H
JH
Department of Anesthesiology, Emory University Hospital, Atlanta, GA 30322, USA.
Pifarre
R
R
Schaff
H V
HV
Horrow
J C
JC
Albus
R
R
Spiess
B
B
Rosengart
T K
TK
Murray
J
J
Clark
R E
RE
Smith
P
P
D000368:Aged; D007611:Aprotinin / Q000008:administration & dosage* / Q000009:adverse effects; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D001803:Blood Transfusion; D001810:Blood Volume; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D011183:Postoperative Complications / Q000453:epidemiology; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000453:epidemiology; D012086:Reoperation; D012307:Risk Factors; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects
D006490:Hemostatics; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin