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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

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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.

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Acknowledgment

Dr. Kevin Liou is supported by the Australian National Health and Medical Research Council (grant no. GNT1094045) and National Heart Foundation of Australia (ID: 100688) Postgraduate Scholarship. The trial is supported in part by the research grant from the Prince of Wales Hospital Foundation.

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Authors and Affiliations

  1. Eastern Heart Clinic, Prince of Wales Hospital, Level 3, Campus Center, Barker Street, Randwick, Sydney, NSW, 2031, Australia

    Kevin Liou, Nigel Jepson, Elizabeth Anne Russell & Sze-Yuan Ooi

  2. Prince of Wales Clinical School, University of New South Wales, Sydney, Australia

    Kevin Liou, Nigel Jepson, Nicolas Buckley, Vivien Chen & Sze-Yuan Ooi

  3. School of Medical Sciences, Sydney Medical School, University of Sydney, Sydney, Australia

    Nicolas Buckley

  4. Lowy Cancer Research Center, University of New South Wales, Sydney, Australia

    Vivien Chen

  5. Redox Cell Signaling Group, Center for Vascular Research & School of Medical Sciences, University of New South Wales, Sydney, Australia

    Shane Thomas

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  1. Kevin Liou
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Correspondence to Kevin Liou.

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Liou, K., Jepson, N., Buckley, N. et al. 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. Cardiovasc Drugs Ther 30, 169–175 (2016). https://doi.org/10.1007/s10557-016-6641-x

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