Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass: a randomized trial

Abstract

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 (> 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.

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.