Mechanistic Study of the Effect of Endothelin SNPs in Microvascular Angina – protocol of the PRIZE Endothelin Sub-Study
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Authors
Abraham, George
Morrow, Andrew
Oliveira, Joana
Davenport, Emma
Berry, Colin
Hoole, Stephen
Publication Date
2022-04Journal Title
International Journal of Cardiology - Heart and Vasculature
ISSN
2352-9067
Publisher
Elsevier Scientific Publishers Ireland
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Abraham, G., Morrow, A., Oliveira, J., Weir-McCall, J., Davenport, E., Berry, C., Davenport, A., & et al. (2022). Mechanistic Study of the Effect of Endothelin SNPs in Microvascular Angina – protocol of the PRIZE Endothelin Sub-Study. International Journal of Cardiology - Heart and Vasculature https://doi.org/10.1016/j.ijcha.2022.100980
Abstract
Introduction
Microvascular angina (MVA) is a common cause of ischemia with non-obstructive coronary arteries (INOCA) and limited therapeutic options are available to those affected. Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathophysiology of MVA. A large randomised, double blinded, placebo controlled crossover trial, the PRecIsion medicine with ZibotEntan in microvascular angina (PRIZE) trial is currently underway, investigating an endothelin receptor antagonist – Zibotentan, as a new drug treatment for microvascular angina. The trial uses a 'precision medicine' approach by preferential selection of those with higher ET-1 expression conferred by the PHACTR1 minor G allele single nucleotide polymorphism (SNP). The incidence of this SNP occurs in approximately one third of the population therefore a considerable number of screened patients will be ineligible for randomisation and the treatment phase of the trial.
Methods
In the PRIZE Endothelin (ET) Sub-Study, patients screened out of the PRIZE trial will be genotyped for other genetic variants in the ET-1 pathway. These will be correlated with phenotypic characteristics including exercise tolerance, angina severity and quantitative measures of microvascular function on cardiovascular MRI as well as mechanistic data on endothelin pathway signalling.
Conclusions
The study will provide a comprehensive genotype and phenotype bio-resource identifying novel ET-1 genotypes to inform the potential wider use of endothelin receptor antagonists for this indication.
Sponsorship
Wellcome Trust [WT107715/Z/15/Z, APD], British Heart Foundation [CB, RE/18/6134217], Medical Research Council [CB, MR/S018905/1], ].Jon Moulton Charity Trust [GRA, SPH]
Funder references
Wellcome Trust (107715/Z/15/Z)
MRC (via University of Glasgow) (303684)
Identifiers
External DOI: https://doi.org/10.1016/j.ijcha.2022.100980
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333540
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