Mechanistic study of the effect of Endothelin SNPs in microvascular angina - Protocol of the PRIZE Endothelin Sub-Study.
View / Open Files
Authors
Abraham, George R
Morrow, Andrew J
Oliveira, Joana
Davenport, Emma E
Berry, Colin
Hoole, Stephen P
Publication Date
2022-04Journal Title
Int J Cardiol Heart Vasc
ISSN
2352-9067
Publisher
Elsevier BV
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Abraham, G. R., Morrow, A. J., Oliveira, J., Weir-McCall, J., Davenport, E. 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.. Int J Cardiol Heart Vasc https://doi.org/10.1016/j.ijcha.2022.100980
Abstract
INTRODUCTION: Microvascular angina 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 microvascular angina. 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
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.