Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass  Stanton K Shernan, MD, Jane C.K Fitch, MD, Nancy A Nussmeier, MD, John C Chen, MD, Scott A Rollins, PhD, Christopher F Mojcik, MD, PhD, Kevin J Malloy, PhD, Thomas G Todaro, MD, JD, Thomas Filloon, PhD, Steven W Boyce, MD, Deepak M Gangahar, MD, Michael Goldberg, MD, Lawrence J Saidman, MD, Dennis T Mangano, MD, PhD  The Annals of Thoracic Surgery  Volume 77, Issue 3, Pages 942-949 (March 2004) DOI: 10.1016/j.athoracsur.2003.08.054

Fig 1 Patient study disposition. Only patients with at least one of the following risk factors for adverse postoperative ischemic events were considered for enrollment: age greater than or equal to 60 years; history of congestive heart failure (New York Heart Association class III or IV); prior coronary artery bypass graft surgery (CABG); greater than or equal to two myocardial infarctions, or a myocardial infarction within 14 days of screening; neurologic event (cerebrovascular accident, transient ischemic attack, or carotid endarterectomy); creatinine greater than or equal to 1.3 mg/dL. Patients with an active infection, prior monoclonal antibody or gammaglobulin exposure, or a history of complement deficiency, malignancy, uncontrolled diabetes, recent cardiogenic shock, hematologic, renal disease (creatinine > 2 mg/dL), or hepatic disease were excluded. The Annals of Thoracic Surgery 2004 77, 942-949DOI: (10.1016/j.athoracsur.2003.08.054)

Fig 2 Pharmacodynamics: mean hemolytic activity plus or minus standard error versus time of greater than 96 hours after placebo or pexelizumab bolus for all three treatment groups. The Annals of Thoracic Surgery 2004 77, 942-949DOI: (10.1016/j.athoracsur.2003.08.054)

Fig 3 Primary efficacy analysis. Data are presented as the incidence of the primary composite endpoint (death, myocardial infarction [MI], left ventricular [LV] dysfunction, or new central neurological system [CNS]), and its individual components for all treatment groups through postoperative day 30. There were no significant differences between either of the pexelizumab-treatment groups versus the placebo group on the composite, nor any of its individual components. Error bars represent the standard error of the occurrence rate. (CK-MB = myocardial-specific isoform of creatine kinase.) The Annals of Thoracic Surgery 2004 77, 942-949DOI: (10.1016/j.athoracsur.2003.08.054)

Fig 4 Peak myocardial-specific isoform of creatine kinase (CK-MB) concentrations in the isolated coronary artery bypass graft (CABG) placebo group and the bolus plus infusion group. Statistical significance is attained at all peak CK-MB concentrations of greater than 70 ng/mL. Lower concentrations of CK-MB release may occur as an unavoidable consequence of surgical manipulation, trauma, and inadequate myocardial protection. Increased CK-MB release may be indicative of clinically significant myocardial injury. Error bars represent the standard error of percentage of isolated CABG patients for each peak CK-MB concentration. (*p values are nominal and unadjusted.) The Annals of Thoracic Surgery 2004 77, 942-949DOI: (10.1016/j.athoracsur.2003.08.054)

Fig 5 Post hoc assessment of pexelizumab efficacy in isolated coronary artery bypass graft patients across all treatment groups. Data are presented as the incidence of the composite of death or myocardial infarction (any postoperative myocardial-specific isoform of creatine kinase [CK-MB] ≥ 100 ng/mL) and its individual components through postoperative day 30. Compared with the placebo group, the pexelizumab bolus plus infusion group reduced myocardial infarction by 66% (2.7% vs 7.8%; p = 0.01). Death rates for the pexelizumab bolus plus infusion and placebo populations were 0.4% versus 1.9%, respectively (p = 0.22). Error bars represent the standard error of the occurrence rate. The Annals of Thoracic Surgery 2004 77, 942-949DOI: (10.1016/j.athoracsur.2003.08.054)