People with chronic chest pain who received a coronary sinus reducer (CSR, Shockwave Medical) experienced significant reductions in the daily number of chest pain episodes but did not show evidence of increased overall blood flow to the heart compared with patients who received a placebo procedure, six-month results from the ORBITA-COSMIC trial, presented today at the American College of Cardiology (ACC) 2024 scientific session (6–8 April, Atlanta, USA), have shown.
Investigators in the trial, ORBITA-COSMIC, say that the results indicate that they can tell patients who are receiving the device that their symptoms are more likely to improve, although the precise mechanism behind this improvement remains unclear.
The study, which was published simultaneously in The Lancet alongside its presentation at ACC 2024, met one of its primary endpoints by showing symptom improvements with the CSR but did not meet the main primary endpoint that was designed to determine the mechanism by which the CSR might work. The findings show no difference between groups in terms of an MRI-based assessment of overall blood flow to the heart tissue.
“We don’t have a positive endpoint in terms of the primary hypothesis of how this device works, but it does seem to reduce angina frequency in patients with refractory angina,” said Rasha Al-Lamee (Imperial College Healthcare NHS Trust, London, UK), the study’s senior author. “This is a population of patients who are very symptomatic and have no further options for treatment.”
The Reducer is a balloon-expandable, hourglass-shaped device that is designed to establish a narrowing in the coronary sinus which is intended to result in an increase in back pressure which will lead to a redistribution of blood into the ischaemic myocardium to help reduce angina symptoms.
ORBITA-COSMIC was designed to build on previous studies, which have suggested that the CSR can improve angina symptoms by using more robust placebo-controlled methodology and endpoints assessing the impact of the device on blood flow. The researchers randomised 51 patients at six UK hospitals to receive either a CSR implant or a placebo procedure, which involved sedation but no implant.
All participants had symptomatic angina, ischaemia and coronary artery disease with no further medical or interventional options at the start of the study. Participants underwent cardiac magnetic resonance imaging (MRI) and treadmill exercise test before their procedure and at the end of a blinded six-month follow-up period. Patients also recorded their angina symptoms daily with a smartphone application.
Results for the trial’s secondary endpoints followed a similar pattern. Angina frequency lessened among those who received CSR across several measures, including the Seattle Angina Questionnaire, although no difference was found for other measures such as treadmill exercise time. Patients who received CSR also saw an improvement in sub-endocardial to sub-epicardial ratio of stress myocardial blood flow, which may suggest some redistribution of myocardial blood flow but no difference in terms of other factors assessed with the cardiac MRI.
Most of the patients who received the CSR implant did not experience complete elimination of angina symptoms but did report reductions in the number of daily pain episodes and the number of days on which they experienced pain.
“For a patient, what they want to know is whether the device will help them to feel better. With the results of this placebo-controlled trial, we can tell them that their symptoms are more likely to improve with the reducer,” Al-Lamee said. “However, we still need to work out why.”
The CSR device was found to be generally safe. Two patients in the CSR group experienced blood clots, but no heart attacks or deaths occurred.
The device is already approved for use in Europe and the UK, so the findings could potentially increase its use there, Al-Lamee said.
The device is not yet approved by the U.S. Food and Drug Administration (FDA) for use in the USA, although an FDA-approved trial is currently underway.
The researchers plan to conduct further analyses to determine whether particular groups of patients may be more likely to benefit from CSR implantation. They also plan to conduct more detailed analyses to further investigate the mechanism of action involved.
