ORBITA-COSMIC Evaluates Coronary Sinus Reducer to Treat Refractory Angina

April 8, 2024—The placebo-controlled ORBITA-COSMIC study met one of its primary endpoints by showing symptom improvement with a coronary sinus reducer (CSR) at 6 months; however, it did not meet the main primary endpoint, which was designed to determine the mechanism by which the CSR might work.

Patients with chronic chest pain who received a CSR experienced significant reductions in the daily number of chest pain episodes. However, in terms of a MRI-based assessment of overall blood flow to the heart tissue, the findings showed no difference between the group that received the CSR implant and the group that received the placebo procedure.

Michael J. Foley, MBBS, presented the findings from ORBITA-COSMIC at ACC.24, the American College of Cardiology’s Annual Scientific Session held April 6-8 in Atlanta, Georgia. The study was simultaneously published online by Dr. Foley et al in The Lancet.

ORBITA-COSMIC’s senior investigator is Rasha Al-Lamee, MBBS, a clinical academic interventional cardiology consultant at Imperial College Healthcare NHS Trust and a clinical reader at Imperial College London in London, United Kingdom. The study is funded by the United Kingdom Medical Research Council and Imperial Healthcare Charity.

“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,” commented Dr. Al-Lamee in the ACC press release. “This is a population of patients who are very symptomatic and have no further options for treatment.”

The CSR is an hourglass-shaped stent designed to narrow the vein that collects blood from the coronary sinus and drives oxygen-rich blood back into areas of the heart muscle that may not be receiving enough blood.

As summarized in the ACC press release, ORBITA-COSMIC focused on patients with angina not adequately controlled with available treatments. It was designed to build on previous studies that suggested the CSR can improve angina symptoms by using more robust placebo-controlled methodology and endpoints assessing the impact of the device on blood flow.

In the study, the investigators randomized 51 patients at six hospitals in the United Kingdom to receive either a CSR implant or a placebo procedure, which involved sedation but no implant.

All patients had symptomatic angina, ischemia, and coronary artery disease with no further medical or interventional options at the start of the study. The patients underwent a cardiac MRI and treadmill exercise test before their procedure and at the end of a blinded 6-month follow-up period. Patients also recorded their angina symptoms daily with a smartphone application.

The trial’s two primary endpoints were angina symptoms as assessed with the smartphone application and blood flow to the heart assessed with a cardiac MRI.

At 6 months, patients who received the CSR implant were 40% more likely to report a reduction in the number of daily angina episodes than those who received the placebo procedure but showed no difference in terms of overall blood flow to the heart.

The ACC press release noted that results for the trial’s secondary endpoints had a similar pattern. Angina frequency lessened among patients who received CSR across several measures, including the Seattle Angina Questionnaire, but no difference was found for other measures such as treadmill exercise time.

Patients who received CSR also saw an improvement in subendocardial to subepicardial 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 cardiac MRI.

Most 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.

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, reported the investigators in the ACC press release.

“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,” stated Al-Lamee. “However, we still need to work out why.”

Dr. Al-Lamee further noted that the CSR device is already approved for use in Europe and the United Kingdom, so the findings could potentially increase its use there. The device is not yet approved by the FDA for use in the United States, where it is currently being investigated in an FDA-approved trial.

The investigators 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, stated the ACC press release.