Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass: a randomized trial.
BACKGROUND
Inflammation and ischemia-reperfusion injury during coronary artery bypass graft (CABG) surgery requiring cardiopulmonary bypass are associated with postoperative myocardial infarction (MI) and mortality.


OBJECTIVE
To determine the efficacy and safety of pexelizumab, a C5 complement inhibitor, in reducing perioperative MI and mortality in CABG surgery.


METHODS
A randomized, double-blind, placebo-controlled trial, including 3099 patients (> or = 18 years) undergoing CABG surgery with or without valve surgery at 205 hospitals in North America and Western Europe from January 2002 to February 2003.


METHODS
Patients were randomly assigned to receive intravenous pexelizumab (2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours; n = 1553) or placebo (n = 1546) 10 minutes before undergoing the procedure.


METHODS
The primary composite end point was the incidence of death or MI within 30 days of randomization in those undergoing CABG surgery only (n = 2746). Secondary analyses included the intent-to-treat analyses of death or MI composite at days 4 and 30 in all 3099 study patients.


RESULTS
After 30 days, 134 (9.8%) of 1373 of patients receiving pexelizumab vs 161 (11.8%) of 1359 of patients receiving placebo (relative risk, 0.82; 95% confidence interval, 0.66-1.02; P =.07) died or experienced MI in the CABG surgery only population. In the intent-to-treat analyses, 178 (11.5%) of 1547 patients receiving pexelizumab vs 215 (14.0%) of 1535 receiving placebo died or experienced MI (relative risk, 0.82; 95% confidence interval, 0.68-0.99; P =.03). The trial was not powered to detect a reduction in mortality alone.


CONCLUSIONS
Compared with placebo, pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction 30 days after the procedure among all 3099 patients undergoing CABG with or without valve surgery.
Verrier
Edward D
ED
Division of Cardiothoracic Surgery, University of Washington School of Medicine, Seattle 98195-6310, USA. edver@u.wash.edu
Shernan
Stanton K
SK
Taylor
Kenneth M
KM
Van de Werf
Frans
F
Newman
Mark F
MF
Chen
John C
JC
Carrier
Michel
M
Haverich
Axel
A
Malloy
Kevin J
KJ
Adams
Peter X
PX
Todaro
Thomas G
TG
Mojcik
Christopher F
CF
Rollins
Scott A
SA
Levy
Jerrold H
JH
D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002315:Cardiopulmonary Bypass; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D003165:Complement System Proteins / Q000378:metabolism; D001026:Coronary Artery Bypass / Q000379:methods* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D057127:Single-Chain Antibodies; D016019:Survival Analysis
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D057127:Single-Chain Antibodies; D003165:Complement System Proteins; C402724:pexelizumab