Abstract 12908: Alpha-1 Anti-trypsin Inhibits the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction
Introduction: Alpha-1 anti-trypsin (AAT) is an anti-inflammatory protein abundant in the plasma. Studies in mice have shown anti-inflammatory and cardioprotective properties of plasma derived AAT in experimental myocardial infarction (MI).
Hypothesis: Plasma derived AAT (Prolastin C) inhibits the acute inflammatory response in patients with ST-segment elevation myocardial infarction (STEMI).
Methods: Ten patients with acute STEMI were enrolled in an open-label single-arm treatment study of Prolastin C at 60 mg/kg intravenously within 12 hours of admission. High-sensitivity C reactive protein (CRP) and plasma AAT levels were determined at admission, 72 hours and 14 days, and followed clinically for up to 12 weeks for the occurrence of new onset heart failure (HF), recurrent MI or death. Twenty patients with STEMI enrolled in 2 prior clinical trials with identical inclusion criteria, and were randomly assigned to placebo served as historical controls. Data is presented as median and interquartile range, and analyzed using the Mann Whitney test.
Results: All 10 patients tolerated the infusion of Prolastin C without any adverse in-hospital events. CRP levels at presentation were not statistically different between the Prolastin C and placebo groups (Figure). Prolastin C treatment significantly increased plasma AAT levels at 72 hours from 149 [116-189] to 203 [185-225] mg/dl (P=0.005), and significantly lower area-under-the-curve for CRP levels (Figure), primarily due to a significantly smaller increase between admission and 72 hours (delta CRP +1.7 [0.2-9.4] vs +21.1 [3.1-38.0] mg/l, P=0.007). One patient (10%) in the Prolastin C group died suddenly in the sleep 8 weeks after STEMI, and none (0%) had new onset HF or recurrent MI (Table).
Conclusions: A single administration of plasma-derived AAT, Prolastin C, is well tolerated, significantly inhibits the acute inflammatory response, and is associated with overall favorable outcomes in patients with STEMI.
Author Disclosures: A. Abbate: Research Grant; Modest; Grifols. Other Research Support; Modest; Swedish Orphan Biovitrum. Research Grant; Significant; Novartis. B.W. Van Tassell: None. S. Christopher: None. N. Abouzaki: None. C. Sonnino: None. C. Oddi: None. S. Carbone: None. R. Melchior: None. C. Roberts: None. M.C. Kontos: None. M. Peberdy: None. S. Toldo: None. C. Dinarello: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.