title: Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial.
abstract: BACKGROUND
  Complement, activated during myocardial ischemia and reperfusion, causes myocardial damage through multiple processes. The COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial was performed to determine the effect of pexelizumab, a C5 complement inhibitor, on infarct size in patients with ST-segment-elevation myocardial infarction (MI) undergoing primary percutaneous coronary intervention.
  
  
  RESULTS
  In COMMA, 960 patients with MI (20% isolated inferior MI) were randomized to placebo, pexelizumab 2.0-mg/kg bolus, or pexelizumab 2.0-mg/kg bolus and 0.05-mg/kg per h infusion for 20 hours. Infarct size by creatine kinase-MB area under the curve, the primary outcome, did not differ significantly between groups (placebo median, 4393; bolus pexelizumab, 4526; bolus plus infusion pexelizumab, 4713 [ng/mL] x h; P=0.89 for bolus versus placebo; P=0.76 for bolus plus infusion versus placebo), nor did the composite of 90-day death, new or worsening heart failure, shock, or stroke (placebo, 11.1%; bolus, 10.7%; bolus plus infusion, 8.5%). The ninety-day mortality rate was significantly lower with pexelizumab bolus plus infusion (1.8% versus 5.9% with placebo; nominal P=0.014); the bolus-only group had an intermediate mortality rate (4.2%).
  
  
  CONCLUSIONS
  In patients with ST-elevation MI undergoing percutaneous coronary intervention, pexelizumab had no measurable effect on infarct size. However, the significant reduction in mortality suggests that pexelizumab may benefit patients through alternative novel mechanisms and provides impetus for additional investigation.
authors.affiliation: Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715, USA. grang001@mc.duke.edu
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: W Douglas
authors.initials: WD
authors.lastname: Weaver
authors.forename: Pierre
authors.initials: P
authors.lastname: Theroux
authors.forename: Judith S
authors.initials: JS
authors.lastname: Hochman
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Filloon
authors.forename: Scott
authors.initials: S
authors.lastname: Rollins
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Todaro
authors.forename: Jose C
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D017024:Chemotherapy, Adjuvant; D003182:Complement C5 / Q000037:antagonists & inhibitors*; D003402:Creatine Kinase / Q000032:analysis; D052279:Creatine Kinase, MB Form; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D057127:Single-Chain Antibodies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D007527:Isoenzymes; D057127:Single-Chain Antibodies; C402724:pexelizumab; D003402:Creatine Kinase; D052279:Creatine Kinase, MB Form