乌鸦传媒

ATLANTA -- For people with stable coronary artery disease and refractory angina, a coronary sinus reducer (CSR) implant showed a symptom alleviation benefit in the small placebo-controlled ORBITA-COSMIC trial.

The number of self-reported daily angina episodes shifted downward significantly among people randomized to the Neovasc Reducer intervention instead of a sham procedure (OR 1.40, 95% credible intervals [CrI] 1.08-1.83), reported Michael Foley, MBBS, of Imperial College London, at this year's American College of Cardiology (ACC) annual conference.

Despite the device's purported mechanism of benefit, however, myocardial blood flow in ischemic segments did not improve with the coronary sinus reducer over placebo (difference 0.06 ml/min/g, 95% CrI -0.09 to 0.20).

Foley noted that while there was no improvement in transmural myocardial perfusion, there was improvement in subendocardial perfusion -- the Reducer's mechanism of action nevertheless remains uncertain.

The ORBITA-COSMIC study manuscript was published simultaneously in .

This is an "important" trial as the refractory angina patient population is "incredibly challenging," said ACC session discussant Timothy Henry, MD, of The Christ Hospital in Cincinnati. With their limited options, "these patients are miserable," he said, adding that some work points to coronary flow reserve as a potential mechanism of action by the Reducer device.

"Although CSR was at first regarded as a niche option because of advancements in revascularization techniques, it has gained momentum recently with the increase in prevalence of refractory angina, especially among frail individuals," commented Caterina Monti, MD, PhD, of University of Milan, and Anna Palmisano, MD, of IRCCS San Raffaele Scientific Institute, Milan, in .

The duo cited a hypothesis that coronary sinus reducer therapy helps "collateral networks originating from the left coronary arteries, providing supplementary perfusion to ischemic territories."

The Reducer has been available in the European market for over a decade for people with chest pain and no other options for revascularization. The implant is an hourglass-shaped mesh implanted percutaneously into the coronary sinus for the improvement of myocardial perfusion. The device acts on the cardiac venous circulation and is supposed to redistribute blood toward ischemic territories.

This therapy currently has a class IIb recommendation in European guidelines on chronic coronary syndromes. This was based on the COSIRA trial that showed that Reducer implants resulted in no improvement in self-reported angina but an improvement in physician-assessed Canadian Cardiovascular Society (CCS) class.

American regulators remain unswayed by the coronary sinus reducer. In 2020, an advisory committee in considering potential FDA approval. As expected, the agency declined to approve the Reducer but allowed the trial to launch with a more objective primary endpoint: change in exercise tolerance time over 6 months.

Henry, the co-principal investigator for COSIRA-II, suggested that there is still a question of whether the best endpoint in an angina trial going forward is treadmill exercise time or angina.

Foley advocated for a daily angina reporting app, such as the one used in ORBITA-COSMIC, in part due to the advantage of having multiple data points across time.

He and his colleagues conducted the double-blind trial at six U.K. hospitals from 2021 to 2023. Study candidates had to undergo cardiac MRI, fill out symptom and quality-of-life questionnaires, and take a treadmill exercise test before entering a 2-week symptom assessment phase during which they logged their angina symptoms using the trial's dedicated smartphone app.

After identifying adults with refractory angina and stable coronary artery disease, evidence of ischemic segments, with no other treatment options, the investigators enrolled 61 patients. Of those, 51 reached randomization between the CSR or placebo procedure under deep sedation and auditory isolation.

Participants were 86% men, 49% white, and 35% Asian. Nearly all participants were in CCS class III or IV. Most had undergone prior coronary artery bypass grafting surgery (86%) or previous percutaneous coronary intervention (55%). The median stress myocardial blood flow was 1.08 mL/min/g in ischemic segments.

After the study treatment, patients agreed to a 6-month follow-up period in which they continued to log daily symptoms on the app.

As for safety, Foley's group reported two coronary sinus reducer embolization events but no acute coronary syndrome events or deaths in either study arm.

ORBITA-COSMIC had the major limitations of a small sample and relatively short follow-up.

Nevertheless, the double blinding and rigorous statistical methods of the trial put "these results at a high level of evidence," Monti and Palmisano wrote.