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ATLANTA, GA — Despite failing to increase perfusion as hypothesized, a coronary sinus reducer (CSR) in a sham-controlled randomized trial meaningfully reduced angina and improved quality of life in patients not considered candidates for any alternative therapies.

The CSR device, which was associated with a low rate of complications, was validated as "a therapeutic option for patients with few other choices," according to the trial's senior investigator, Rasha K. Al-Lamee, MBBS, PhD, a clinical academic interventional cardiology consultant associated with the Imperial College Healthcare Trust, London, England.

CSR devices consist of a small mesh that is introduced into the coronary sinus percutaneously. Produced by several companies, these have been listed as an option for refractory angina in a class IIB European Society of Cardiology guideline recommendation since 2019. This study, called ORBITA-COSMIC, was investigator-led and received no funding from the industry.

New Study Follows Previous Sham-Controlled Trial

A previous sham-controlled trial, called COSIRA, was published almost 10 years ago. This trial also associated CSR with improved control of angina symptoms and quality of life but did not explore the purported mechanism of action, which is improved perfusion in the areas of the heart thought to be causing angina, said Al-Lamee.

In ORBITA-COSMIC, presented in a late-breaking clinical trials session at the annual meeting of the American College of Cardiology and published simultaneously in The Lancet, one of the two co-primary endpoints was a change in myocardial blood flow. It was measured at baseline and at end of the study in ischemic segments identified with adenosine stress perfusion on a cardiac magnetic resonance scan.

The other primary endpoint was the number of daily angina episodes as recorded by patients on a smartphone app, reported Michael J. Foley, MBBS, a training research fellow at Imperial College London, London, England, who presented the data.

Of the 51 patients randomized to a CSR (Neovasc Reducer, Shockwave Medical) or a sham procedure, 50 were included in the intention-to-treat analysis after a failed implantation in the experimental arm. More than 80% had previous coronary artery bypass grafting, and more than 50% had a prior percutaneous intervention. Almost all (> 90%) presented with Canadian Cardiovascular Society class III or higher angina.

40% Increase in Angina-Free Days

At the end of 6 months, there was a 40% increase in the odds ratio (OR) of having days free of angina (OR, 1.40), said Foley, adding that statistical probability was calculated as 99.4%.

Even though the relative benefit was gained slowly and first emerged about 70 days into the study, the greater control of angina persisted across several methods of evaluating the data, Foley noted. For example, patients receiving the CSR device relative to those who had undergone a sham procedure had 13 more angina-free days over a 6-month period (84.5 vs 71.5 days).

The improved control of angina correlated with an improvement in quality of life as measured with the Seattle Angina Questionnaire and the MacNew Heart Disease health-related quality of life questionnaire. For both, the improvements were statistically significant and clinically meaningful, according to Foley, who reported specifically that the improvement for the MacNew score translated into a 99.4% probability of benefit.

Despite this reduction in angina, the study was not able to prove the hypothesis that angina is relieved by improved perfusion, which was the other primary endpoint.

"No benefit of CSR over placebo was detected in stress myocardial blood flow in segments designated ischemic at enrollment," Foley said.

Only One Measure of Perfusion Improved

In addition to the key measure of perfusion, other measures, such as myocardial perfusion reserve and myocardial blood flow at rest, were negative for a CSR advantage. The exception was an improvement in the endocardial-to-epicardial ratio, which was unchanged on imaging in nonischemic segments, but did improve significantly in ischemic segments. The probability of improvement on this measure was 98.2%, Foley said.

Other than the inability to deploy CSR in one patient, there were no other periprocedural complications, but two patients in the experimental arm vs none in the sham-controlled arm developed a CSR embolization. There were no other serious adverse events, such as bleeding, stroke, or myocardial infarction.

Treadmill exercise at the end of the study improved a modest 40 seconds among those who received CSR relative to a sham procedure (61.4 vs 20.4 sec), but Foley suggested that functional improvements are unlikely in the enrolled population, patients who were no longer responding to antianginal medications, had multiple comorbidities, and were extremely limited in their activity level.

"Despite maximal antianginal therapy, almost all patients had class III or IV angina with no further treatments available for symptom control," Foley reiterated. He contended that CSR might be the only practical option for the types of patients enrolled in this study.

Challenging Patients

The invited ACC discussant, Jennifer A. Rymer, MD, an assistant professor and interventional cardiologist at Duke University School of Medicine, Durham, North Carolina, agreed that the types of patients enrolled in ORBITA-COSMIC are challenging.

"The patients in this trial were on a median of three to four antianginals but still with a heavy symptom burden," Rhymer pointed out. She said the quality of life of these patients is "miserable," and any option that relieves symptoms might be worth considering.

Even though the trial was unable to confirm that the benefit stems from improved perfusion of ischemic myocardial segments, she pointed out that this "well-done, sham-controlled" design substantiates the premise that patient lives can be improved.

CSR is also associated with substantial costs and non-negligible risk for complications, but Timothy D. Henry, MD, chair of clinical research at the Lindner Center for Research at Christ Hospital, Cincinnati, Ohio, agreed that the data support CSR as an option in selected patients.

The types of patients enrolled in this study are "incredibly challenging," Henry said. But given the benefits, risks, and costs of CSR, he indicated that it is appropriate to use CSR judiciously.

Al-Lamee reported financial relationships with Abbott, Janssen, Medtronic, Menarini, Omniprex, Philips, and Servier. Foley reported financial relationships with Menarini and Philips. Rymer reported financial relationships with Abiomed, Chiesi Farmaceutici S.p.A., Idorsia, and Pfizer. Henry reported financial relationships with Abbott, Boston Scientific, Chiesi Farmaceutici S.p.A., Neovasc, and XyloCor.

Ted Bosworth is a medical journalist based in New York City.