on August 18, 2003
Published online before print August 18, 2003, doi: 10.1161/01.CIR.0000087404.53661.F8
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Submitted on March 13, 2003
From the Duke Clinical Research Institute (K.W.M., C.B.G.), Durham, NC; Heart Institute (J.C.N.), University of Sao Paulo Medical School, Sao Paulo, Brazil; National Institute of Cardiology (W.R.), Warsaw, Poland; 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 (C.F.M.), Cheshire, Conn; and University of Alberta (P.W.A.), Edmonton, Alberta, Canada. * To whom correspondence should be addressed. E-mail: mahaf002{at}mc.duke.edu.
Background--Complement activation mediates myocardial damage that occurs during ischemia and reperfusion through multiple pathways. We performed 2 separate, parallel, double-blind, placebo-controlled trials to determine the effects of pexelizumab (a novel C5 complement monoclonal antibody fragment) on infarct size in patients receiving reperfusion therapy: COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) and COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA). The COMPLY trial is reported here. Methods and Results--Overall, 943 patients with acute ST-segment elevation myocardial infarction (MI) (20% with isolated inferior MI) receiving fibrinolysis were randomly assigned <6 hours after symptom onset to placebo, pexelizumab 2.0-mg/kg bolus, or pexelizumab 2.0-mg/kg bolus plus 0.05 mg/kg per h for 20 hours. Infarct size determined by creatine kinase-MB area under the curve was the primary analysis, which included patients who received at least some study drug and fibrinolysis (n=920). The median infarct size did not differ by treatment (placebo, 5230; bolus, 4952; bolus plus infusion, 5557 [ng/mL] · h; bolus versus placebo, P=0.85; bolus plus infusion versus placebo, P=0.81), nor did the 90-day composite incidence of death, new or worsening congestive heart failure, shock, or stroke (placebo, 18.6%; bolus, 18.4%; bolus plus infusion, 19.7%). Pexelizumab inhibited complement for 4 hours with bolus-only dosing and for 20 to 24 hours with bolus-plus-infusion dosing, with no increase in infections. Conclusions--When used adjunctively with fibrinolysis, pexelizumab blocked complement activity but reduced neither infarct size by creatine kinase-MB assessment nor adverse clinical outcomes.
Revised on June 23, 2003
Accepted on June 24, 2003
Effect of Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Fibrinolysis in Acute Myocardial Infarction. The COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) Trial
Kenneth W. Mahaffey MD*,
Key words: myocardial infarction • fibrinolysis • reperfusion • inflammation
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