title: Design and Rationale for the Endothelin-1 Receptor Antagonism in the Prevention of Microvascular Injury in Patients with non-ST Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention (ENDORA-PCI) Trial.
abstract: OBJECTIVE
  Peri-procedural myocardial infarction (PMI) occurs in a small but significant portion of patients undergoing percutaneous intervention (PCI). The underlying mechanisms are complex and may include neurohormonal activation and release of vasoactive substances resulting in disruption of the coronary microcirculation. Endothelin in particular has been found in abundance in atherosclerotic plaques and in systemic circulation following PCI, and may be a potential culprit for PMI through its action on microvascular vasoconstriction, and platelet and neutrophil activation. In this study we aim to characterize the behavior of the coronary microcirculation during a PCI with the index of microvascular resistance (IMR) and the effect of peri-procedural endothelin antagonism.
  
  
  METHODS
  The ENDORA-PCI trial is a randomized, double-blind, placebo-controlled, single-center clinical trial designed to evaluate the efficacy of endothelin antagonism in attenuating the peri-procedural rise in IMR as a surrogate marker for PMI. The patients of interest are those with non-ST elevation acute coronary syndrome (NSTEACS) undergoing PCI, and we aim to recruit 52 patients overall to give the study a power of 80 % at an α level of 5 %. Patients will be randomized in a 1:1 fashion to either Ambrisentan, an endothelin antagonist, or placebo, prior to their PCI. IMR will be measured before and after PCI. The primary endpoint is the difference in peri-procedural changes in patients' IMR between the two groups.
  
  
  CONCLUSIONS
  The ENDORA-PCI study will investigate whether endothelin antagonism with Ambrisentan attenuates the peri-procedural rise in IMR in patients with NSTEACS undergoing PCI, and thus potentially the risk of PMI.
authors.affiliation: Eastern Heart Clinic, Prince of Wales Hospital, Level 3, Campus Center, Barker Street, Randwick, Sydney, NSW, 2031, Australia. kevin.liou@sesiahs.health.nsw.gov.au.|Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. kevin.liou@sesiahs.health.nsw.gov.au.
authors.forename: Kevin
authors.initials: K
authors.lastname: Liou
authors.affiliation: Eastern Heart Clinic, Prince of Wales Hospital, Level 3, Campus Center, Barker Street, Randwick, Sydney, NSW, 2031, Australia.|Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Jepson
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.|School of Medical Sciences, Sydney Medical School, University of Sydney, Sydney, Australia.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Buckley
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.|Lowy Cancer Research Center, University of New South Wales, Sydney, Australia.
authors.forename: Vivien
authors.initials: V
authors.lastname: Chen
authors.affiliation: Redox Cell Signaling Group, Center for Vascular Research & School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Shane
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Eastern Heart Clinic, Prince of Wales Hospital, Level 3, Campus Center, Barker Street, Randwick, Sydney, NSW, 2031, Australia.
authors.forename: Elizabeth Anne
authors.initials: EA
authors.lastname: Russell
authors.affiliation: Eastern Heart Clinic, Prince of Wales Hospital, Level 3, Campus Center, Barker Street, Randwick, Sydney, NSW, 2031, Australia.|Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Sze-Yuan
authors.initials: SY
authors.lastname: Ooi
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D000293:Adolescent; D017023:Coronary Angiography / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists / Q000627:therapeutic use*; D006801:Humans; D008833:Microcirculation / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism; D062645:Percutaneous Coronary Intervention / Q000379:methods; D044022:Receptor, Endothelin A / Q000378:metabolism*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D065130:Endothelin A Receptor Antagonists; D044022:Receptor, Endothelin A
keywords: Endothelin; Index of microvascular resistance; Peri-procedural myocardial infarction; Trial design