Kevin Liou1,2, Nigel Jepson3,4, Nicolas Buckley4,5, Vivien Chen4,6, Shane Thomas7, Elizabeth Anne Russell3, Sze-Yuan Ooi3,4. 1. 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. 2. Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. kevin.liou@sesiahs.health.nsw.gov.au. 3. Eastern Heart Clinic, Prince of Wales Hospital, Level 3, Campus Center, Barker Street, Randwick, Sydney, NSW, 2031, Australia. 4. Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. 5. School of Medical Sciences, Sydney Medical School, University of Sydney, Sydney, Australia. 6. Lowy Cancer Research Center, University of New South Wales, Sydney, Australia. 7. Redox Cell Signaling Group, Center for Vascular Research & School of Medical Sciences, University of New South Wales, Sydney, Australia.
Abstract
PURPOSE: 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. CONCLUSION: 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.
RCT Entities:
PURPOSE: 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. CONCLUSION: 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.
Entities:
Keywords:
Endothelin; Index of microvascular resistance; Peri-procedural myocardial infarction; Trial design
Authors: David Carrick; Caroline Haig; Nadeem Ahmed; Jaclyn Carberry; Vannesa Teng Yue May; Margaret McEntegart; Mark C Petrie; Hany Eteiba; Mitchell Lindsay; Stuart Hood; Stuart Watkins; Andrew Davie; Ahmed Mahrous; Ify Mordi; Ian Ford; Aleksandra Radjenovic; Keith G Oldroyd; Colin Berry Journal: Circulation Date: 2016-11-01 Impact factor: 29.690