Thromb Haemost 2014; 112(01): 176-182
DOI: 10.1160/TH13-10-0832
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Peri-interventional endothelin-A receptor blockade improves long-term outcome in patients with ST-elevation acute myocardial infarction

Christopher Adlbrecht*
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Raphael Wurm*
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Michael Humenberger
2   Department of Trauma Surgery, Medical University of Vienna, Vienna, Austria
,
Martin Andreas
3   Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
,
Bassam Redwan
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Klaus Distelmaier
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Günter Klappacher
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
,
Irene M. Lang
1   Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria
› Author Affiliations

Financial support: The study was supported by funds of the Oesterreichische Nationalbank (Anniversary Fund, project number: #12758) to CA, the Austrian Society of Cardiology to CA (2005, 2009 and 2014) and the Hans und Blanca Moser Stiftung to BR (2007). There are no conflicts of interest.
Further Information

Publication History

Received: 09 October 2013

Accepted after major revision: 08 February 2014

Publication Date:
01 December 2017 (online)

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Summary

Endothelin (ET)-1 is a pro-fibrotic vasoconstrictive peptide causing microvascular dysfunction and cardiac remodelling after acute ST-elevation myocardial infarction (STEMI). It acts via two distinct receptors, ET-A and ET-B, and is involved in inflammation and atherogenesis. Patients with posterior-wall STEMI were randomly assigned to intravenous BQ-123 at 400 nmol/minute (min) or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention (n=54). Peripheral blood samples were drawn at baseline as well as after 24 hours and 30 days. Myeloperoxidase (MPO), as a marker of neutrophil activation and matrix metalloproteinase 9 (MMP-9), a marker of extracellular matrix degradation were measured in plasma. Clinical follow-up was conducted by an investigator blinded to treatment allocation over three years. During the median follow-up period of 3.6 years (interquartile range [IQR] 3.3–4.1) we observed a longer event-free survival in patients randomised to receive BQ-123 compared with patients randomised to placebo (mean 4.5 years (95% confidence interval: 3.9–5) versus mean 3 years (2.2–3.7), p=0.031). Patients randomised to ET-A receptor blockade demonstrated a greater reduction of MPO levels from baseline to 24 hours compared to placebo-treated patients (-177 ng/ml (IQR 103–274) vs –108 ng/ml (74–147), p=0.006). In addition, a pronounced drop in MMP-9 levels (-568 ng/ml (44–1157) vs –117 ng/ml (57–561), p=0.018) was observed. There was no significant difference in amino-terminal propetide of pro-collagen type III levels. In conclusion, short-term administration of BQ-123 leads to a reduction in MPO, as well as MMP-9 plasma levels and to a longer event-free survival in patients with STEMI.

ClinicalTrials.gov Identifier: NCT00502528

* CA and RW contributed equally to this work.