Effects of Prolastin C (Plasma-Derived Alpha-1 Antitrypsin) on the Acute Inflammatory Response in Patients With ST-Segment Elevation Myocardial Infarction (from the VCU-Alpha 1-RT Pilot Study)

被引：40

作者：

Abbate, Antonio ^{[1
]}

Van Tassell, Benjamin Wallace ^{[2
]}

Christopher, Sanah ^{[1
]}

Abouzaki, Nayef Antar ^{[1
]}

Sonnino, Chiara ^{[1
,2
]}

Oddi, Claudia ^{[1
,2
]}

Carbone, Salvatore ^{[1
,2
]}

Melchior, Ryan David ^{[1
,2
]}

Gambill, Michael Lucas ^{[1
]}

Roberts, Charlotte Susan ^{[1
]}

Kontos, Michael Christopher ^{[1
]}

Peberdy, Mary Ann ^{[1
,2
]}

Toldo, Stefano ^{[1
]}

Vetrovec, George Wayne ^{[1
]}

Biondi-Zoccai, Giuseppe ^{[3
]}

Dinarello, Charles Anthony ^{[4
]}

机构：

[1] Virginia Commonwealth Univ, Pauley Heart Ctr, Richmond, VA 23284 USA

[2] Virginia Commonwealth Univ, Dept Pharmacotherapy & Outcomes Sci, Richmond, VA USA

[3] Univ Roma La Sapienza, Latina, Italy

[4] Univ Colorado, Dept Med, Aurora, CO USA

来源：

AMERICAN JOURNAL OF CARDIOLOGY | 2015年 / 115卷 / 01期

关键词：

INTERLEUKIN-1; ANAKINRA; DISEASE; TRIALS;

D O I：

10.1016/j.amjcard.2014.09.043

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：8 / 12

页数：5

共 12 条

[1] Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction [J].