Assessment of Pexelizumab in Acute Myocardial Infarction - APEX AMI – Presented at AHA 2006
The goal of the trial was to evaluate the use of pexelizumab, an anti-C5 complement monoclonal antibody fragment, compared with placebo, among patients undergoing primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (MI).
Patients Enrolled: 5,745
Mean Follow Up: 90 days
Mean Patient Age: Median age, 61 years
Acute MI within 6 hours of symptom onset, anterior or high-risk inferior MI, planned performance of primary PCI, and age ≥18 years
Use of thrombolytic therapy for treatment of the index MI, complement deficiency, isolated low-risk inferior wall MI, or suspected neisserial infection
All-cause mortality through 30 days
Death, heart failure, or shock at 30 days
Patients undergoing primary PCI were randomized in a double-blind manner to pexelizumab (2 mg/kg bolus plus 0.05 mg/kg/h for 24 hours; n = 2,860) or matching placebo bolus and infusion (n = 2,885).
Inferior infarctions were present in 41% of patients and diabetes in 16%. Nearly half (43%) were smokers. Patients were transferred for PCI from an outside medical center in 36% of cases. Median time from symptom onset to PCI was 3.3 hours, and median time from study drug administration to PCI was approximately 0.25 hours. Stents were used in 89% of patients and glycoprotein IIb/IIIa inhibitors in 69%.
The trial was discontinued early. There was no difference in the primary endpoint of death at 30 days (4.1% for pexelizumab vs. 3.9% for placebo, hazard ratio [HR] 1.04, p = 0.78). There was also no difference in the composite of death, heart failure, or shock at 30 days (9.0% vs. 9.2%, HR 0.98, p = 0.81). Clinical events by 90 days did not differ, including death (4.9% vs. 4.5%), heart failure (4.8% each), shock (3.4% vs. 3.5%), and reinfarction (3.0% vs. 2.4%), for pexelizumab versus placebo, respectively. Sepsis at 14 days, which was a relatively infrequent event, trended lower in the pexelizumab group (0.56% vs. 0.90%, HR 0.62, p = 0.13).
Among patients with ST elevation MI undergoing primary PCI, treatment with pexelizumab was not associated with a difference in mortality at 30 days compared with placebo.
Prior data from the COMMA study demonstrated a reduction in mortality at 6 months with pexelizumab compared with placebo in patients treated with primary PCI, but this trial was not designed specifically to address this issue given the small size of the trial, which was powered to look at infarct size. In addition to the present study, the PRIMO-CABG II trial also showed no significant benefit on death or MI with pexelizumab in the setting of bypass surgery. Performance of PCI and bypass surgery can cause reperfusion injury and increase inflammation, which this compound was designed to inhibit. Limited success has been reported to date for therapies that target reperfusion injury, although other agents are currently being investigated.
The APEX AMI Investigators. Pexelizumab for Acute ST-Elevation Myocardial Infarction in Patients Undergoing Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial. JAMA 2007;297 43-51.
Presented by Dr. Paul W. Armstrong at the American Heart Association Annual Scientific Sessions, Chicago, IL, November 2006.
Keywords: Antibodies, Monoclonal, Humanized, Inflammation, Infarction, Myocardial Infarction, Sepsis, Coronary Disease, Complement C5, Percutaneous Coronary Intervention, Stents, Reperfusion Injury, Heart Failure, Diabetes Mellitus, Single-Chain Antibodies
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