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J Thorac Cardiovasc Surg 2006;131:352-356
© 2006 The American Association for Thoracic Surgery

Surgery for Acquired Cardiovascular Disease

Inhibition of complement activation by pexelizumab reduces death in patients undergoing combined aortic valve replacement and coronary artery bypass surgery

^a Montreal Heart Institute, Montreal, Quebec, Canada
^b Hammersmith Hospital, NHLI Imperial College School of Medicine, London, United Kingdom
^c Hannover Medical School, Hannover, Germany
^d Kaiser Permanente Medical Center, University of Hawaii, Honolulu, Hawaii
^e Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
^f Duke Clinical Research Institute, Duke University, Durham, NC
^g Emory University Hospital, Emory University, Atlanta, Ga
^h University Hospital Gasthuisberg, Leuven, Belgium
ⁱ Proctor & Gamble Pharmaceuticals, Egham, United Kingdom
^j Proctor & Gamble Pharmaceuticals, Mason, Ohio
^k Alexion Pharmaceuticals, Inc, Cheshire, Conn
^l University of Washington, School of Medicine, Seattle, Wash
^m Department of Cardiovascular Surgery, Hôpital Georges Pompidou, Paris, France

Received for publication June 14, 2005; revisions received September 23, 2005; accepted for publication October 7, 2005.

^_* Address for reprints: M. Carrier, MD, Research Center, Montreal Heart Institute, 5000 Belanger St East, Montreal, Quebec H1T 1C8, Canada (Email: michel.carrier{at}icm-mhi.org).

OBJECTIVE: We sought to evaluate the effects of pexelizumab, a C5 complement inhibitor, on death and myocardial infarction in patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery.

METHODS: The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary Artery Bypass Graft surgery trial, a phase III prospective, randomized, double-blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The primary end point was the composite of death, myocardial infarction, or both at postoperative day 30 in patients undergoing coronary artery bypass grafting without valve surgery. Postoperative myocardial infarction was defined as a creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or new Q-wave evidence of myocardial infarction by postoperative day 30. Because patients undergoing coronary artery bypass grafting with a valve procedure were not included in the primary population, separate analysis of death and myocardial infarction was conducted in 218 patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery.

RESULTS: Of the 353 patients randomized to any valve procedure, 106 (61%) underwent combined aortic valve replacement and coronary artery bypass grafting in the pexelizumab treatment group compared with 112 (63%) patients in the placebo group. Coronary artery bypass grafting was performed with 1 or more internal thoracic artery grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179 (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11 (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial infarction 30 days after surgical intervention was identical in the 2 groups, but the study was not designed to detect differences in this cohort of patients.

CONCLUSIONS: Inhibition of complement activation by pexelizumab resulted in a decreased mortality at 180 days among 218 patients who underwent combined aortic valve replacement and coronary artery bypass grafting surgery. Additional studies are warranted to confirm this decrease in mortality with pexelizumab in combined aortic valve replacement and coronary artery bypass grafting procedures.

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