Terminal Complement Blockade With Pexelizumab During Coronary Artery Bypass Graft Surgery Requiring Cardiopulmonary Bypass: A Randomized Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 291; no. 19; pp. 2319 - 2327
• Main Authors: Verrier, Edward D, Shernan, Stanton K, Taylor, Kenneth M, Van de Werf, Frans, Newman, Mark F, Chen, John C, Carrier, Michel, Haverich, Axel, Malloy, Kevin J, Adams, Peter X, Todaro, Thomas G, Mojcik, Christopher F, Rollins, Scott A, Levy, Jerrold H, for the PRIMO-CABG Investigators
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 19-05-2004
• Subjects: Aged; Anti-Inflammatory Agents - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Cardiopulmonary Bypass; Clinical trials; Complement C5 - antagonists & inhibitors; Complement System Proteins - metabolism; Coronary Artery Bypass - methods; Coronary Artery Bypass - mortality; Coronary vessels; Double-Blind Method; Female; Heart attacks; Humans; Immunomodulators; Male; Medical sciences; Mortality; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - prevention & control; Pharmacology. Drug treatments; Prescription drugs; Single-Chain Antibodies; Surgery; Survival Analysis; Coronary artery; Surgical anastomosis; Complement; Pexelizumab; Cardiopulmonary bypass; Immunomodulator; Medicine; Chemotherapy; Treatment; Aortocoronary; Bypass; Surgery; Blood vessel; Clinical trial; Graft; Inhibitor; Combined treatment; Circulatory system
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.291.19.2319

CONTEXT 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. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial, including 3099
patients (≥ 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. INTERVENTIONS 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. MAIN OUTCOME MEASURES 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.