Circulation. 2003;108:1184-1190
Published online before print August 18, 2003, doi: 10.1161/01.CIR.0000087447.12918.85
Published online before print August 18, 2003, doi: 10.1161/01.CIR.0000087447.12918.85
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(Circulation. 2003;108:1184.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
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
From Duke Clinical Research Institute (C.B.G., K.W.M.), Durham, NC; Henry Ford Hospital (W.D.W.), Detroit, Mich; Montreal Heart Institute (P.T.), Montreal, Quebec, Canada; Columbia University (J.S.H.), New York, NY; Procter & Gamble Pharmaceuticals (T.G.F., T.G.T.), Mason, Ohio; Alexion Pharmaceuticals, Inc (S.R.), Cheshire, Conn; Heart Institute (J.C.N.), University of Sao Paulo Medical School, Sao Paulo, Brazil; National Institute of Cardiology (W.R.), Warsaw, Poland; and University of Alberta (P.W.A.), Edmonton, Alberta, Canada.
Correspondence to Christopher B. Granger, MD, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715. E-mail grang001{at}mc.duke.edu
Received March 13, 2003; revision received June 23, 2003; accepted June 24, 2003.
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.
Methods and 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] · 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.
Key Words: myocardial infarction • angioplasty • inflammation • reperfusion
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