title: 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).
abstract: 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.
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia. Electronic address: abbatea@yahoo.com.
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.affiliation: Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Benjamin Wallace
authors.initials: BW
authors.lastname: Van Tassell
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Sanah
authors.initials: S
authors.lastname: Christopher
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Nayef Antar
authors.initials: NA
authors.lastname: Abouzaki
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sonnino
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Oddi
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Carbone
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Ryan David
authors.initials: RD
authors.lastname: Melchior
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael Lucas
authors.initials: ML
authors.lastname: Gambill
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Charlotte Susan
authors.initials: CS
authors.lastname: Roberts
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Michael Christopher
authors.initials: MC
authors.lastname: Kontos
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia; Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Peberdy
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
authors.affiliation: VCU Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: George Wayne
authors.initials: GW
authors.lastname: Vetrovec
authors.affiliation: Sapienza University of Rome, Latina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Charles Anthony
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D010865:Pilot Projects; D012189:Retrospective Studies; D015842:Serine Proteinase Inhibitors / Q000493:pharmacokinetics; D013997:Time Factors; D016896:Treatment Outcome; D000515:alpha 1-Antitrypsin / Q000493:pharmacokinetics*
chemical_list: D015415:Biomarkers; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D002097:C-Reactive Protein