Inhibiting the Inflammatory Injury After Myocardial Ischemia Reperfusion With Plasma-Derived Alpha-1 Antitrypsin: A Post Hoc Analysis of the VCU-α1RT Study

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.

Conflict of interest statement

The authors report no conflicts of interest.

Figures

FIGURE 1

Time-to-peak CK-MB and estimates of infarct size. We provide a scheme on how the different time-based variables and infarct size estimates are calculated, and a table with the median and interquartile range for each variable divided by group.

FIGURE 2

Estimated effect of plasma-derived AAT (Prolastin C) on infarct size. Left panel shows estimated infarct size measured as area under the curve (AUC) for CK-MB in the Prolastin C–treated patients and historic placebo-treated patients. Right panel shows differences in time-to-peal to CK-MB between groups.

FIGURE 3

Interval change in AAT plasma levels and surrogate end points. Correlation between the increase in AAT plasma at 72 hours and infarct size estimate is shown in the Prolastin C–treated patients. Right panel shows correlation between interval change in plasma AAT levels and left ventricular ejection fraction at follow up.

FIGURE 4

Survival free from HF events. One patient in the Prolastin C group died suddenly, and none experienced HF during midterm follow-up, as compared with 1 patient who died and 9 patients who experienced HF (N = 10, 50%) in the historical placebo cohort (P = 0.07).