Coronary Sinus Reducer for the treatment of refractory angina: a randomised, placebo-controlled trial (ORBITA-COSMIC)
File(s)
Author(s)
Foley, Michael
Type
Thesis
Abstract
Background
The coronary sinus reducer (CSR) is proposed to reduce angina in stable coronary artery disease (CAD) by improving myocardial perfusion. Its placebo-controlled effect is uncertain.
Methods
ORBITA-COSMIC is a double-blind, randomised trial of CSR versus a placebo procedure, conducted at six UK hospitals. Patients with angina, stable CAD, ischaemia, and no further options for treatment were enrolled. They completed a quantitative stress perfusion cardiac MRI (CMR), questionnaires, and exercise testing, before entering a 2-week symptom assessment phase using a smartphone application (ORBITA-app). Patients were randomised 1:1 to CSR or a placebo procedure and completed blinded follow-up with daily ORBITA-app reporting. At 6 months, the assessments were repeated. The primary outcome was stress myocardial blood flow (MBF) in segments designated ischaemic at enrolment. The primary symptom outcome was the number of daily angina episodes. Analysis used the intention-to-treat principle and Bayesian methodology. The study is registered with clinicaltrials.gov (NCT04892537).
Findings
Between May 26, 2021, and June 28, 2023, 61 patients were enrolled and 51 were randomised. 25 patients were assigned CSR and 26 the placebo procedure. 57% of cardiac segments were ischaemic at enrolment with median stress MBF of 1·08 (IQR 0·77 to 1·41). MBF in segments ischaemic at enrolment did not improve with CSR compared to placebo (0·06ml/min/g, 95% CrI -0·09 to 0·20, Pr(Benefit) 78.8%). Daily angina episodes were reduced with CSR compared to placebo (OR 1·40, 95% CrI 1·08 to 1·83, Pr(Benefit)=99·4%). There were two CSR embolisations, no acute coronary syndrome events, and no deaths.
Interpretation
In patients with angina, stable CAD, ischaemia, and no further options for antianginal therapies, while there was little evidence the CSR improved transmural myocardial perfusion, it improved angina compared to placebo.
The coronary sinus reducer (CSR) is proposed to reduce angina in stable coronary artery disease (CAD) by improving myocardial perfusion. Its placebo-controlled effect is uncertain.
Methods
ORBITA-COSMIC is a double-blind, randomised trial of CSR versus a placebo procedure, conducted at six UK hospitals. Patients with angina, stable CAD, ischaemia, and no further options for treatment were enrolled. They completed a quantitative stress perfusion cardiac MRI (CMR), questionnaires, and exercise testing, before entering a 2-week symptom assessment phase using a smartphone application (ORBITA-app). Patients were randomised 1:1 to CSR or a placebo procedure and completed blinded follow-up with daily ORBITA-app reporting. At 6 months, the assessments were repeated. The primary outcome was stress myocardial blood flow (MBF) in segments designated ischaemic at enrolment. The primary symptom outcome was the number of daily angina episodes. Analysis used the intention-to-treat principle and Bayesian methodology. The study is registered with clinicaltrials.gov (NCT04892537).
Findings
Between May 26, 2021, and June 28, 2023, 61 patients were enrolled and 51 were randomised. 25 patients were assigned CSR and 26 the placebo procedure. 57% of cardiac segments were ischaemic at enrolment with median stress MBF of 1·08 (IQR 0·77 to 1·41). MBF in segments ischaemic at enrolment did not improve with CSR compared to placebo (0·06ml/min/g, 95% CrI -0·09 to 0·20, Pr(Benefit) 78.8%). Daily angina episodes were reduced with CSR compared to placebo (OR 1·40, 95% CrI 1·08 to 1·83, Pr(Benefit)=99·4%). There were two CSR embolisations, no acute coronary syndrome events, and no deaths.
Interpretation
In patients with angina, stable CAD, ischaemia, and no further options for antianginal therapies, while there was little evidence the CSR improved transmural myocardial perfusion, it improved angina compared to placebo.
Version
Open Access
Date Issued
2024-10-31
Date Awarded
2025-06-01
Copyright Statement
Attribution-Non Commercial-No Derivatives 4.0 International Licence (CC BY-NC-ND)
Advisor
Al-Lamee, Rasha
Francis, Darrel
Cole, Graham
Sponsor
Medical Research Council
Grant Number
MR/V001620/1
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)