1. Inhibiting the Inflammatory Injury After Myocardial Ischemia Reperfusion With Plasma-Derived Alpha-1 Antitrypsin: A Post Hoc Analysis of the VCU-α1RT Study.
- Author
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Abouzaki NA, Christopher S, Trankle C, Van Tassell BW, Carbone S, Mauro AG, Buckley L, Toldo S, and Abbate A
- Subjects
- Anti-Inflammatory Agents adverse effects, Biomarkers blood, C-Reactive Protein metabolism, Creatine Kinase, MB Form blood, Humans, Inflammation blood, Inflammation etiology, Inflammation Mediators blood, Infusions, Intravenous, Myocardial Reperfusion Injury blood, Myocardial Reperfusion Injury etiology, Myocardial Reperfusion Injury pathology, Myocardium metabolism, Myocardium pathology, Pilot Projects, ST Elevation Myocardial Infarction blood, ST Elevation Myocardial Infarction diagnostic imaging, Time Factors, Treatment Outcome, alpha 1-Antitrypsin adverse effects, Anti-Inflammatory Agents administration & dosage, Inflammation prevention & control, Myocardial Reperfusion Injury prevention & control, Percutaneous Coronary Intervention adverse effects, ST Elevation Myocardial Infarction surgery, alpha 1-Antitrypsin administration & dosage
- Abstract
Background: Despite the benefits of reperfusion in limiting myocardial injury, the infarct size continues to expand after reperfusion because of secondary inflammatory injury. Plasma-derived alpha-1 antitrypsin (AAT) inhibits the inflammatory injury in myocardial ischemia and reperfusion. To explore the effects of plasma-derived AAT on the inflammatory response to ischemia-reperfusion injury, we analyzed time-to-reperfusion and enzymatic infarct size estimates in a post hoc analysis of the VCU-α1RT clinical trial (clinicaltrials.gov NCT01936896)., Methods: Ten patients with ST-segment elevation acute myocardial infarction (STEMI) were enrolled in an open-label, single-arm treatment study of Prolastin C, plasma-derived AAT, at 60 mg/kg infused intravenously within 12 hours of reperfusion. Biomarkers were measured serially over the first 72 hours, and patients were followed clinically for the occurrence of new-onset heart failure, recurrent MI, or death. Twenty patients with STEMI who had been enrolled in previous randomized trials with identical inclusion/exclusion criteria and had been assigned to placebo served as historical controls., Results: Time to percutaneous coronary intervention and time to drug did not significantly differ between groups. AAT-treated patients had a significantly shorter time-to-peak creatine kinase myocardial band (CK-MB) values (525 [480-735] vs. 789 [664-959] minute, P = 0.005) and CK-MB area under the curve (from 1204 [758-2728] vs. 2418 [1551-4289] U·day, P = 0.035), despite no differences in peak CK-MB (123 [30-196] vs. 123 [71-213] U/mL, P = 0.71)., Conclusions: A single administration of Prolastin C given hours after reperfusion in patients with STEMI led to a significant shorter time to peak and area under the curve for CK-MB, despite similar peak CK-MB values. These preliminary data support the hypothesis that Prolastin C shortens the duration of the ischemia-reperfusion injury in patients with STEMI.
- Published
- 2018
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