Mahaffey Kenneth W, Granger Christopher B, Nicolau Jose C, Ruzyllo Witold, Weaver W Douglas, Theroux Pierre, Hochman Judith S, Filloon Thomas G, Mojcik Christopher F, Todaro Thomas G, Armstrong Paul W
Duke Clinical Research Institute, Durham, NC 27715, USA.
Circulation. 2003 Sep 9;108(10):1176-83. doi: 10.1161/01.CIR.0000087404.53661.F8. Epub 2003 Aug 18.
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.
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] x 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.
When used adjunctively with fibrinolysis, pexelizumab blocked complement activity but reduced neither infarct size by creatine kinase-MB assessment nor adverse clinical outcomes.
补体激活通过多种途径介导缺血再灌注期间发生的心肌损伤。我们进行了2项独立、平行、双盲、安慰剂对照试验，以确定培昔利珠单抗（一种新型C5补体单克隆抗体片段）对接受再灌注治疗患者梗死面积的影响：溶栓治疗心肌梗死中的补体抑制（COMPLY）试验和血管成形术治疗心肌梗死中的补体抑制（COMMA）试验。本文报告COMPLY试验。
总体而言，943例急性ST段抬高型心肌梗死（MI）患者（20%为单纯下壁MI）在症状发作后<6小时接受溶栓治疗，被随机分配接受安慰剂、2.0mg/kg负荷剂量的培昔利珠单抗或2.0mg/kg负荷剂量加0.05mg/kg每小时持续20小时的培昔利珠单抗治疗。通过肌酸激酶-MB曲线下面积确定梗死面积是主要分析指标，其中包括接受至少部分研究药物和溶栓治疗的患者（n=920）。梗死面积中位数在各治疗组间无差异（安慰剂组为5230；负荷剂量组为4952；负荷剂量加输注组为5557[ng/mL]×小时；负荷剂量组与安慰剂组比较，P=0.85；负荷剂量加输注组与安慰剂组比较，P=0.81），90天内死亡、新发或加重的充血性心力衰竭、休克或中风的复合发生率也无差异（安慰剂组为18.6%；负荷剂量组为18.4%；负荷剂量加输注组为19.7%）。单纯负荷剂量给药时培昔利珠单抗抑制补体4小时，负荷剂量加输注给药时抑制补体20至24小时，且感染无增加。
与溶栓治疗联合使用时，培昔利珠单抗可阻断补体活性，但通过肌酸激酶-MB评估既未减小梗死面积，也未改善不良临床结局。
