the values of troponin T and creatine kinase-MB (CK-MB) were reduced by 36% and 57%, respectively, as compared to 18 control patients who had AMI and did not receive C1-INH therapy. The other component of the complement cascade that has been the target of anticomplement therapy in MI is C5. In a dog model of cardiac ischemia induced by ligation of the left circumﬂex artery, cardiac lymph obtained from the dogs several hours after reperfusion was able to activate neutro- phils (Dreyer et al 1992). However, this effect was completely abolished when anti-C5a was added to the cardiac lymph. It was also shown that the monocyte chemotactic activity of cardiac lymph in the ﬁrst few hours after reperfusion is almost completely due to C5a (Birdsall et al 1997). More directly, in a porcine model of ischemia-reperfusion, a recombinant human C5 antagonist, CGS 32359, was able to inhibit neutrophil activation and reduce infarct size (Riley et al 2000). Finally, in a rat model of ischemia-reperfusion, a monoclonal antibody against C5 reduced apoptosis, necrosis, and neutrophil inﬁltration (Vakeva et al 1998). A large randomized, placebo-controlled phase II study of 960 patients, the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial, investigated the effect of anti-C5 therapy in AMI (Granger et al 2003). In this study, the anti-C5 agent pexelizumab (Alexion Pharmaceuticals, Cheshire, Connecticut, USA) was used. Patients with AMI who underwent primary PCI therapy were randomized to placebo, pexelizumab bolus given just before revascularization, and pexelizumab bolus plus subsequent infusion for 20 hours. There was no difference between the groups with respect to infarct size as determined by CK-MB area under the curve (AUC), but there was a signiﬁcant beneﬁt in 90-day mortality rate for the bolus plus infusion group (1.8%) as compared to the placebo group (5.9%). In a substudy of the COMMA trial, there was a sig- niﬁcant difference in the hemodynamic status of the groups treated with pexelizumab versus placebo after correcting for age, race, and MI location (Armstrong et al 2006). It was shown that this improved hemodynamic status was not due to infarct size, degree of ST-segment elevation, or extent of reperfusion. In another substudy of the COMMA trial, it was shown that higher CRP and interleukin-6 (IL-6) levels at base- line, 24 hours, and 72 hours were associated with increased death, and that elevated CRP, IL-6, and tumor necrosis factor-α levels were associated with more cardiogenic shock or death within 90 days of treatment (Théroux et al 2005). Despite similar serum levels of CRP and IL-6 at baseline, Biologics:Targets & Therapy 2008:2(4) Anticomplement therapy the pexelizumab-treated groups had signiﬁcantly lower CRP and IL-6 levels at 24 hours, but by 72 hours, the values were similar between different groups. The COMMA trial was the ﬁrst part of a two-part phase II clinical trial called the Complement And ReDuction of INfarct size after Angioplasty or Lytics (CARDINAL) program. The results of the second part of the CARDINAL study, known as the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) trial, were also reported in 2003 (Mahaffey et al 2003). In this study, 943 patients who underwent ﬁbrinolysis for ST-segment elevation MI (STEMI) were randomized similarly to the way patients were random- ized in the COMMA trial. It was shown that pexelizumab lowered complement activity but had no effect on infarct size as measured by CK-MB AUC or on adverse clinical outcomes in the 90 days following treatment. The follow-up to the CARDINAL program was a large, prospective, multicenter, randomized, double-blind, placebo- controlled phase III trial in which 5745 patients who had a STEMI treated with PCI were randomized to either placebo or treatment with pexelizumab as a bolus just before PCI and then as a 24-hour infusion after revascularization therapy (APEX AMI Investigators et al 2007). This trial showed no difference in 30-day all-cause mortality or in the 90-day composite of death, cardiogenic shock, or congestive heart failure. Coronary artery bypass graft surgery, ischemia-reperfusion injury, and cardiopulmonary bypass After revascularization with emergent CABG surgery in the setting of AMI, reperfusion can activate the complement sys- tem, similar to reperfusion with thrombolysis or angioplasty. Also, in cardiac surgery, use of cardiopulmonary bypass (CPB) exposes blood to nonself material in extracorporeal circuits, which in turn activate the alternative complement system. Thus, inhibition of complement activity may be ben- eﬁcial in decreasing inﬂammation and tissue injury resulting from CABG surgery through two mechanisms, prevention of revascularization injury and reduced activation of the complement system associated with exposure of blood to extracorporeal circuits. The effect of C1-INH was studied in 67 patients who underwent emergency CABG surgery for STEMI (Thielmann et al 2006). In this study, a bolus of C1-INH was given during, and another bolus given 6 hours after, surgery. It was shown that if C1-INH was given within 6 hours of the onset of symptoms, troponin I levels were reduced, but 679