@article{3325f9fe047143c196c1d203f6c9f0a4,
title = "ChaMP-CMD: A Phenotype-Blinded, Randomized Controlled, Cross-Over Trial",
abstract = "BACKGROUND: Angina with nonobstructive coronary arteries is a common condition for which no effective treatment has been established. We hypothesized that the measurement of coronary flow reserve (CFR) allows identification of patients with angina with nonobstructive coronary arteries who would benefit from anti-ischemic therapy. METHODS: Patients with angina with nonobstructive coronary arteries underwent blinded invasive CFR measurement and were randomly assigned to receive 4 weeks of amlodipine or ranolazine. After a 1-week washout, they crossed over to the other drug for 4 weeks; final assessment was after the cessation of study medication for another 4 weeks. The primary outcome was change in treadmill exercise time, and the secondary outcome was change in Seattle Angina Questionnaire summary score in response to anti-ischemic therapy. Analysis was on a per protocol basis according to the following classification: coronary microvascular disease (CMD group) if CFR<2.5 and reference group if CFR≥2.5. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). RESULTS: Eighty-seven patients (61±8 years of age; 62% women) underwent random assignment (57 CMD group and 30 reference group). Baseline exercise time and Seattle Angina Questionnaire summary scores were similar between groups. The CMD group had a greater increment (delta) in exercise time than the reference group in response to both amlodipine (difference in delta, 82 s [95% CI, 37-126 s]; P<0.001) and ranolazine (difference in delta, 68 s [95% CI, 21-115 s]; P=0.005). The CMD group reported a greater increment (delta) in Seattle Angina Questionnaire summary score than the reference group in response to ranolazine (difference in delta, 7 points [95% CI, 0-15]; P=0.048), but not to amlodipine (difference in delta, 2 points [95% CI,-5 to 8]; P=0.549). CONCLUSIONS: Among phenotypically similar patients with angina with nonobstructive coronary arteries, only those with an impaired CFR derive benefit from anti-ischemic therapy. These findings support measurement of CFR to diagnose and guide management of this otherwise heterogeneous patient group.",
keywords = "Humans, Female, Male, Ranolazine/therapeutic use, Myocardial Ischemia, Cross-Over Studies, Microvascular Angina, Amlodipine/therapeutic use, Phenotype, Microcirculation, Coronary Circulation, Coronary Artery Disease/drug therapy",
author = "Aish Sinha and Haseeb Rahman and Abdel Douiri and Demir, {Ozan M} and {De Silva}, Kalpa and Brian Clapp and Ian Webb and Ankur Gulati and Pedro Pinho and Utkarsh Dutta and Howard Ellis and Shah, {Ajay M} and Amedeo Chiribiri and Michael Marber and Webb, {Andrew J} and Divaka Perera",
note = "Funding Information: ChaMP-CMD was an investigator-led trial funded by a grant from the Medical Research Council (MR/T029390/1) and sponsored by King{\textquoteright}s College London and Guys{\textquoteright} and St. Thomas{\textquoteright} NHS Foundation Trust. Coauthors acknowledge support from the British Heart Foundation (FS/16/49/32320, CH/1999001/11735, and RE/18/2/34213), the UK National Institute for Health Research (through the Biomedical Research Centre award to King{\textquoteright}s College London and Guy{\textquoteright}s and St Thomas{\textquoteright} Hospital), the Fondation Leducq and the NIHR Clinical Research Network (NIHR CRN). to the authors thank Dr Pavlidis, Dr Morgan, Dr Kaier, Dr Ryan, Mr Ogden, Mr Belford, Ms Dovtartaite, Mr Campbell, Dr Li KamWa, Dr Ezad, and Mr Redmond for helping with data acquisition. Most importantly, the authors would like to thank all their participants and their families for their dedication to this research. Drs Sinha, Rahman, Marber, Webb, and Perera were responsible for the conception and design of the study. Drs Sinha, Webb, Chiribiri, Douiri, Shah, Marber (independent chairperson), and Perera (principal investigator) were members of the steering committee. Drs Sinha, Rahman, and Perera drafted and revised the document, which all authors reviewed and advised on. Drs Sinha, Rahman, Demir, Douiri, Chiribiri, and Perera performed data analysis. Drs Rahman, Demir, De Silva, Clapp, Webb, and Gulati, H. Ellis, U. Dutta, and Dr Perera were responsible for data acquisition in the cardiac catheter laboratory. Dr Douiri was the study statistician. Funding Information: ChaMP-CMD is a phenotype-blinded randomized crossover trial performed at a tertiary referral cardiac center in London, UK. This study was approved by the National Health Service Research Ethics Committee (reference 20/LO/1294), funded by the UK Medical Research Council, and overseen by a trial steering committee. Written informed consent was obtained from all patients before their enrollment. The study protocol was registered before the first patient was enrolled (International Standard Randomised Controlled Trial Number: ISRCTN94728379). Funding Information: The trial was funded by a grant from the Medical Research Council (MR/T029390/1). The funders of the study peer reviewed the study design but had no role in data collection, data analysis, data interpretation, or writing of the report. The first, corresponding, and last authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. Publisher Copyright: {\textcopyright} 2024 Lippincott Williams and Wilkins. All rights reserved.",
year = "2024",
month = jan,
day = "2",
doi = "10.1161/CIRCULATIONAHA.123.066680",
language = "English",
volume = "149",
pages = "36--47",
journal = "Circulation",
issn = "0009-7322",
publisher = "American Heart Association, Inc.",
number = "1",
}
