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Lookup NU author(s): Professor Vijay KunadianORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s).Background Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes. Methods This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal ≥25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist. Results The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom ( n = 35), Republic of Ireland ( n = 2), Holland ( n = 2), and Poland ( n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only). Conclusion This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries. Clinical trial registration https://clinicaltrials.gov/study/NCT04674449 . Unique identifier NCT04674449
Author(s): Ang D, Young R, Taggart D, Carrick D, Chattopadhyay S, Raja Y, Balachandran K, Elghamaz A, Greenwood J, Hoole S, Cotton J, Choudhury A, O'Kane P, Jadhav S, Purcell I, Mitra R, Sabra A, Giblett J, Byrne R, O'Gallagher K, Subkovas E, Rampat R, Anantharam B, Radhakrishnan A, Owens C, Damman P, Guzik B, Collison D, Howarth F, Lennon L, Tolentino P-M, Vicere A, Martin K, Kamdar A, Sykes R, Hanna R, Tan D, Heggie R, Wu O, Welsh P, Ford T, Lang CC, Kunadian V, McConnachie A, Berry C
Publication type: Article
Publication status: Published
Journal: American Heart Journal
Year: 2026
Volume: 301
Online publication date: 06/07/2026
Acceptance date: 04/07/2026
Date deposited: 10/08/2026
ISSN (print): 0002-8703
ISSN (electronic): 1097-6744
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.ahj.2026.107527
DOI: 10.1016/j.ahj.2026.107527
PubMed id: 42409349
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