title: Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial.
abstract: BACKGROUND
  Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents.
  
  
  OBJECTIVE
  To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI.
  
  
  METHODS
  This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006.
  
  
  METHODS
  Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset.
  
  
  METHODS
  The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90.
  
  
  RESULTS
  No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91).
  
  
  CONCLUSIONS
  In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00091637.
authors.affiliation: University of Alberta, Edmonton, Alberta, T6G 2H7 Canada. paul.armstrong@ualberta.ca
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Peter X
authors.initials: PX
authors.lastname: Adams
authors.forename: Christian
authors.initials: C
authors.lastname: Hamm
authors.forename: David
authors.initials: D
authors.lastname: Holmes
authors.forename: William W
authors.initials: WW
authors.lastname: O'Neill
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Todaro
authors.forename: Alec
authors.initials: A
authors.lastname: Vahanian
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D011446:Prospective Studies; D012770:Shock, Cardiogenic / Q000453:epidemiology; D057127:Single-Chain Antibodies; D016019:Survival Analysis
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057127:Single-Chain Antibodies; C402724:pexelizumab