Endotyping-informed therapy for patients with chest pain and no obstructive coronary artery disease: a randomized trial
Conor Bradley, Gemma McKinley, Vanessa Orchard, Christina Tiller, Bethany Stanley, Daniel Ang, Andrew Morrow, Robert Sykes, Pamela Gildea, Maria Petty, Richard Brogan, David Carrick, Damien Collison, Hany Eteiba, Angie Ghattas, Richard Good, Francis R. Joshi, Mitchell Lindsay, Peter McCartney, James McGowan, Ross McGeoch, Keith Robertson, Paul Rocchiccioli, Aadil Shaukat, Stuart Watkins, Peter Kellman, Alex McConnachie, Colin Berry
Abstract
Patients undergoing invasive coronary angiography for the investigation of chest pain commonly do not have obstructive coronary artery disease. In contemporary practice, most of these individuals do not undergo functional diagnostic tests, leaving the cause of the chest pain uncertain. Stress cardiovascular magnetic resonance imaging (MRI) can be used to measure myocardial blood flow, detect coronary microvascular dysfunction and endotype individual patients, but evidence of clinical utility from randomized trials is lacking. This study was a prospective, multicenter, parallel group, 1:1 randomized, controlled superiority trial of adenosine stress cardiovascular MRI-guided management in 250 patients (mean age, 63.3 years; 50.4% female) with chest pain and unobstructed coronary arteries. The primary outcome of the diagnostic study, defined as the reclassification of the initial diagnosis based on the angiogram, occurred in 131 patients (53.0% (95% confidence interval: 46.6-59.3%); P < 0.001), indicating that the primary outcome for the diagnostic study was met. The primary outcome of the randomized trial was the Seattle Angina Questionnaire (SAQ) summary score at 12 months after randomization. The mean ± s.d. SAQ summary scores at 12 months in the intervention and control groups were 70.9 ± 23.6 (21.7 ± 22.6 change from baseline) and 52.1 ± 24.1 (-0.8 ± 20.4 change from baseline) (adjusted mean difference: 20.9 (95% confidence interval: 15.8-26.0)), respectively, indicating that the primary outcome of the randomized trial was met. Improvements were also observed in the prespecified secondary outcome of the EQ-5D-5L questionnaire at 12 months (adjusted mean difference 0.09 (95% confidence interval: 0.04-0.13)). In this study of patients with chest pain and unobstructed coronary arteries, endotyping-informed therapy revised the diagnosis in more than half of the participants and improved angina and health-related quality of life. ClinicalTrials.gov identifier: NCT04805814 .