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(Circulation. 2005;112:I-276 – I-280.)
© 2005 American Heart Association, Inc.

Surgery for Coronary Artery Disease

Aprotinin Decreases Postoperative Bleeding and Number of Transfusions in Patients on Clopidogrel Undergoing Coronary Artery Bypass Graft Surgery

A Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Jan van der Linden, MD, PhD; Gabriella Lindvall, MD; Ulrik Sartipy, MD

From the Department Cardiothoracic Surgery and Anesthesiology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.

Correspondence to Dr Jan van der Linden, Department of Cardiothoracic Surgery and Anesthesiology, Karolinska Institute, Karolinska University Hospital, SE-17176 Stockholm, Sweden. E-mail janvan{at}ki.se

Background— Clopidogrel, an irreversible platelet inhibitor, is used to treat patients with unstable angina. These patients often present for coronary artery bypass graft surgery (CABG) and are at increased risk for perioperative bleeding. The current investigation evaluates the impact of aprotinin on bleeding and transfusion requirements in clopidogrel-treated patients undergoing CABG.

Methods and Results— Seventy-five consecutive patients with unstable angina, administered clopidogrel <5 days before CABG, were randomized. Using a double-blind design, patients received full-dose aprotinin (n =37) or saline (n =38). Elapsed times between the last dose of clopidogrel and start of the operation were similar between the 2 groups [aprotinin, 58±28 hour (mean± SD); control, 54±27 hour; P=0.86], as were age (aprotinin, 66.4±10 years; control, 68.3±10 years; P=0.51), number of distal anastomoses (aprotinin, 3.6±1.0; control, 3.7±1.0; P=0.79), operative times (aprotinin, 192±48 minutes; control, 200±53 minutes; P=0.55), and lowest intraoperative hemoglobin level (aprotinin, 87±14 g/L; control, 88±14 g/L; P=0.60). Postoperative bleeding was 760±350 mL in aprotinin-treated patients versus 1200±570 mL (P<0.001) in control. During the hospital stay, patients in the aprotinin group received 1.2±1.5 and 0.1±0.4 U of erythrocytes and platelets, respectively, versus 2.8±3.2 (P=0.02) and 0.9±1.4 (P=0.002) units in the control. In the aprotinin group, 53% of patients received transfusions, whereas 79% of controls were exposed to blood products (P=0.02).

Conclusions— Intraoperative aprotinin decreases postoperative bleeding and the number of transfusions in patients undergoing CABG and treated with clopidogrel <5 days before surgery.

Key Words: angina • hemorrhage • inhibitors • platelets • surgery