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(Circulation. 2003;108:1176.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

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; Christopher B. Granger, MD; Jose C. Nicolau, MD; Witold Ruzyllo, MD; W. Douglas Weaver, MD; Pierre Theroux, MD; Judith S. Hochman, MD; Thomas G. Filloon, PhD; Christopher F. Mojcik, MD, PhD; Thomas G. Todaro, JD, MD; Paul W. Armstrong, MD, for the COMPLY Investigators

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.

Correspondence to Kenneth W. Mahaffey, MD, PO Box 17969, Duke Clinical Research Institute, Durham, NC 27715. E-mail mahaf002{at}mc.duke.edu

Received March 13, 2003; revision received June 23, 2003; accepted June 24, 2003.

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.

Key Words: myocardial infarction • fibrinolysis • reperfusion • inflammation