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

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.