Pexelizumab and infarct size in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: A delayed enhancement cardiac magnetic resonance substudy from the APEX-AMI Trial

Objectives: The purpose of the study was to understand determinants of infarct size in a primary percutaneous intervention (PCI) population treated with pexelizumab compared with placebo.Background: In the multicenter APEX-AMI (Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction) trial, pexelizumab did not reduce 90-day mortality. Cardiac magnetic resonance (CMR) with delayed enhancement was used in a substudy evaluating infarct size and left ventricular ejection fraction (LVEF). Methods: Consecutive patients undergoing primary PCI for first myocardial infarction (MI) as part of the APEX-AMI trial were enrolled in this substudy at 5 centers. The CMR was completed on days 3 to 5 (n = 99) and day 90 (n = 83) following PCI. Central core lab-masked analyses for quantified LVEF, volumes, and infarct size by planimetry were performed. Results: Patients were 60 ± 12 years of age, male (n = 83 [84%]), had similar time from symptom onset to presentation (median 2.6 h vs. 2.5 h; p = 1.0), and similar baseline ST-segment deviation (13.5 mm vs. 14 mm; p = 0.59) in both groups. Pexelizumab-treated patients had smaller infarct size (day 3 LV 10.5% vs. 16.2%, p = 0.022; day 90 LV 5.9% vs. 12.4%, p = 0.015) and higher LVEF (day 3 50.3% vs. 46.2%, p = 0.073; day 90 53.9% vs. 49.3%, p = 0.036) compared with placebo-treated patients. The median peak creatine kinase in the pexelizumab group was also significantly less than placebo (922 mg/dl vs. 1,973 mg/dl; p = 0.03). Notably, the pexelizumab group had lower Thrombolysis In Myocardial Infarction (TIMI) flow grade pre-PCI (46.9% vs. 75.0%; p = 0.018), a difference not seen in the overall APEX-AMI study. A multivariate model including baseline features and pexelizumab treatment found anterior MI location and pre-PCI TIMI flow to be significant independent predictors infarct size (p = 0.001), whereas pexelizumab was not (p = 0.29). No death, heart failure, or shock was noted in either substudy group at 90 days. Conclusions: In a CMR substudy of pexelizumab in MI, baseline TIMI flow grade and anterior location were the only predictors of infarct size, with a reduction of pre-PCI TIMI flow grade 0 by 28%, leading to a 35% reduction in infarct size. (The APEX-AMI Trial; NCT00091637)Manesh R. Patel, Stephen G. Worthley, Amanda Stebbins, Thorsten Dill, Frank E. Rademakers, Uma S. Velleti, Gregory W. Barsness, Frans Van de Werf, Christian W. Hamm, Paul W. Armstrong, Christopher B. Granger, and Raymond J. Kimhttp://imaging.onlinejacc.org