title: Systemic endothelin receptor blockade in ST-segment elevation acute coronary syndrome protects the microvasculature: a randomised pilot study.
abstract: OBJECTIVE
  ST-elevation acute coronary syndrome (STE-ACS) is characterised by compromised blood flow at the epicardial and microvascular levels. Endothelin-1 (ET-1) is a mediator of microvascular dysfunction and adverse cardiac remodelling. We hypothesised that administration of an endothelin type A (ETA) receptor antagonist (BQ-123; Clinalfa, Läufelfingen, Switzerland) may protect microvascular function.
  
  
  RESULTS
  In this proof-of-concept, randomised, double-blind, placebo-controlled trial, patients with posterior-wall STE-ACS (n=57) were randomly assigned to receive intravenous BQ-123 at 400 nmol/minute or placebo over 60 minutes, starting at the onset of primary percutaneous coronary intervention (PCI). Time to myocardial contrast wash-in of the infarcted segment assessed by first-pass perfusion cardiac magnetic resonance imaging was the primary efficacy endpoint. Secondary endpoints included enzymatic infarct size and left ventricular ejection fraction (LVEF). In patients randomised to BQ-123 we observed shorter microvessel perfusion delays six days after PCI (1.8 sec [0.7-3.4] versus 3.3 sec [2.3-5.4] in placebo-treated patients, p=0.005). The treatment group demonstrated smaller enzymatic infarct sizes (p=0.014). All patients were alive at six months, with an LVEF of 63% (58-69) in patients randomised to BQ-123 and 59% (51-66) in placebo-treated patients (p=0.047).
  
  
  CONCLUSIONS
  Administration of an ETA receptor blocker during primary PCI in patients with STE-ACS is safe and may improve tissue-level perfusion and LVEF.
authors.affiliation: Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Adlbrecht
authors.forename: Martin
authors.initials: M
authors.lastname: Andreas
authors.forename: Bassam
authors.initials: B
authors.lastname: Redwan
authors.forename: Klaus
authors.initials: K
authors.lastname: Distelmaier
authors.forename: Julia
authors.initials: J
authors.lastname: Mascherbauer
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Ioana-Alexandra
authors.initials: IA
authors.lastname: Tilea
authors.forename: Thomas
authors.initials: T
authors.lastname: Neunteufl
authors.forename: Georg
authors.initials: G
authors.lastname: Delle-Karth
authors.forename: Gerald
authors.initials: G
authors.lastname: Maurer
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D000368:Aged; D004311:Double-Blind Method; D004562:Electrocardiography; D065128:Endothelin Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010865:Pilot Projects; D016277:Ventricular Function, Left
chemical_list: D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)