Browse by author
Lookup NU author(s): Professor Ioakim SpyridopoulosORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s).Exercise treadmill testing measures functional capacity and inducible myocardial ischemia and has historically served as an endpoint in phase 2 trials. The Precision Medicine with Zibotentan in Microvascular Angina trial evaluated the selective endothelin-A receptor antagonist zibotentan as a potential disease-modifying therapy for microvascular angina. The trial had a randomized, double-blind, cross-over design and the primary outcome was exercise duration. Compared with placebo, zibotentan at a dose of 10-mg daily for 12-weeks did not improve exercise duration or angina symptoms. In this prespecified analysis, exercise duration was compared across four sequential study visits and the factors associated with within-trial changes were evaluated. Exercise test duration increased progressively in all participants during sequential trial phases, independent of treatment with either zibotentan or placebo. This improvement in exercise duration was associated with female sex (interaction p -value = .0213; effect estimate [95% confidence interval]) 34.95 [13.99, 55.78] seconds, P = .002). In conclusion, the exercise test has limitations as an objective endpoint of efficacy in randomized trials. PRIZE; https://clinicaltrials.gov/study/NCT04097314 Clinicaltrials.gov Registration: NCT04097314.
Author(s): Morrow A, Young R, Abraham GR, Hoole S, Oliveira JMG, Greenwood JP, Arnold JR, Ferreira V, Rakhit R, Galasko G, Sinha A, Perera D, Al-Lamee R, Spyridopoulos I, Kotecha A, Clesham G, Ford TJ, Davenport A, Padmanabhan S, Kaski JC, Weir RA, Sattar N, Ambery P, Welsh P, McConnachie A, Berry C
Publication type: Article
Publication status: Published
Journal: American Heart Journal
Year: 2026
Volume: 297
Print publication date: 01/07/2026
Online publication date: 11/02/2026
Acceptance date: 05/02/2026
Date deposited: 09/03/2026
ISSN (print): 0002-8703
ISSN (electronic): 1097-6744
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.ahj.2026.107379
DOI: 10.1016/j.ahj.2026.107379
Data Access Statement: Data are available on reasonable request. The dataset used in this study is not publicly available, but data access may be granted upon reasonable request
PubMed id: 41687797
Altmetrics provided by Altmetric
