Alpha-1 antitrypsin (AAT) has broad anti-inflammatory and immunomodulating properties
in addition to inhibiting serine proteases. Administration of human plasma–derived
AAT is protective in models of acute myocardial infarction in mice. The objective
of this study was to determine the safety and tolerability of human plasma–derived
AAT and its effects on the acute inflammatory response in non-AAT deficient patients
with ST-segment elevation myocardial infarction (STEMI). Ten patients with acute STEMI
were enrolled in an open-label, single-arm treatment study of AAT at 60 mg/kg infused
intravenously within 12 hours of admission and following standard of care treatment.
C-reactive protein (CRP) and plasma AAT levels were determined at admission, 72 hours,
and 14 days, and patients were followed clinically for 12 weeks for the occurrence
of new onset heart failure, recurrent myocardial infarction, or death. Twenty patients
with STEMI enrolled in previous randomized trials with identical inclusion and/or
exclusion criteria, but who received placebo, served as historical controls. Prolastin
C was well tolerated and there were no in-hospital adverse events. Compared with historical
controls, the area under the curve of CRP levels was significantly lower 14 days after
admission in the Prolastin C group (75.9 [31.4 to 147.8] vs 205.6 [78.8 to 410.9]
mg/l, p = 0.048), primarily due to a significant blunting of the increase occurring
between admission and 72 hours (delta CRP +1.7 [0.2 to 9.4] vs +21.1 [3.1 to 38.0]
mg/l, p = 0.007). Plasma AAT levels increased from admission (149 [116 to 189]) to
203 ([185 to 225] mg/dl) to 72 hours (p = 0.005). In conclusion, a single administration
of Prolastin C in patients with STEMI is well tolerated and is associated with a blunted
acute inflammatory response.
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Article info
Publication history
Published online: October 13, 2014
Accepted:
September 21,
2014
Received in revised form:
September 21,
2014
Received:
August 17,
2014
Footnotes
This study was funded by an American Heart Association, scientist development grant, grant number 10SDG 3030051 to Dr. Abbate. The investigational drug used, Prolastin C, was provided free of charge by Grifols USA L.L.C. (Los Angeles, California), as part of an investigator-initiated study from Dr. Abbate.
The study is registered at the clinical trials registration www.clinicaltrials.gov (NCT01936896).
A complete list of all the VCU-Alpha1RT research staff is included in the Online Appendix section.
See page 12 for disclosure information.
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
