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A Randomized Trial

Edward D. Verrier, MD; Stanton K. Shernan, MD; Kenneth M. Taylor, MD; Frans Van de Werf, MD; Mark F. Newman, MD; John C. Chen, MD; Michel Carrier, MD; Axel Haverich, MD; Kevin J. Malloy, PhD; Peter X. Adams, MD; Thomas G. Todaro, MD, JD; Christopher F. Mojcik, MD, PhD; Scott A. Rollins, PhD; Jerrold H. Levy, MD; for the PRIMO-CABG Investigators

JAMA. 2004;291:2319-2327.

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.

Author Affiliations: University of Washington School of Medicine, Seattle (Dr Verrier); Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (Dr Shernan); Hammersmith Hospital, NHLI Imperial College School of Medicine, London, England (Dr Taylor); University Hospital Gasthuisberg, Leuven, Belgium (Dr Van de Werf); Duke Clinical Research Institute, Duke University, Durham, NC (Dr Newman); Kaiser Permanente Medical Center, University of Hawaii, Honolulu (Dr Chen); Montreal Heart Institute, Montreal, Canada (Dr Carrier); Medizinische Hochschule Hannover, Hannover, Germany (Dr Haverich); Procter & Gamble Pharmaceuticals, Cincinnati, Ohio (Drs Malloy and Todaro); Alexion Pharmaceuticals, Cheshire, Conn (Drs Adams, Mojcik, and Rollins); Emory University Hospital, Emory University, Atlanta, Ga (Dr Levy).

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