A coronary sinus reducer (CSR) improves angina compared with placebo, according to a new study, in which researchers also found the device did not improve transmural myocardial perfusion. Results from the ORBITA-COSMIC study, presented Monday at the American College of Cardiology (ACC) Scientific Sessions 2024 in Atlanta, revealed that one of its primary endpoints was met by showing symptom improvements when the CSR was used. However, researchers were unable to meet the main primary endpoint that determined the mechanism by which the CSR might work. “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 the study’s senior author, Rasha Al-Lamee, MBBS, PhD, in a news release. “This is a population of patients who are very symptomatic and have no further options for treatment.” Blood flow Presenting on behalf of the ORBITA-COSMIC investigators, study team member Michael Foley MD, MBBS, revealed that myocardial blood flow in ischemic segments did not improve with CSR compared with placebo (difference 0.06 mL/min per g (95% credible interval [Crl] -0 09 to 0 20); Probability of Benefit (Pr(Benefit) =78 8%). Foley, who is a cardiology registrar at Imperial College Healthcare NHS Trust in London, also noted the number of daily angina episodes was reduced with CSR compared with placebo (odds ratio [OR] 1.40; [95% Crl 1.08 to1.83]; Pr(Benefit)=99.4%). Further findings of the manuscript that was simultaneously published online in The Lancet, revealed that there were two CSR embolization events in the CSR group, and no acute coronary syndrome events or deaths in either group. “For a patient, what they want to know is whether the device will help them to feel better,” said Al-Lamee, who is a clinical academic interventional cardiology consultant at Imperial College Healthcare NHS Trust. “With the results of this placebo-controlled trial, we can tell them that their symptoms are more likely to improve with the reducer. However, we still need to work out why.” Consistent results Commenting on the research, Caterina Monti, MD, PhD, from the University of Milan, and Anna Palmisano, MD, from the IRCCS San Raffaele Scientific Institute in Milan, said the results were “mostly in line” with previous work describing improvement in patients with refractory angina treated with CSR. “Foley and colleagues confirmed the CMR evidence of flow redistribution towards the ischemic myocardium with the robustness of a randomized study and the advantage of a quantitative CMR approach,” said the two commentators. “Further studies could delve deeper into this subject, clarifying the minimum ischemic burden triggering benefits from CSR implantation along with its potential value in patients with chronic total occlusion of the right coronary artery, to avoid an a-priori preclusion of CSR implantation in this group.” Future CSR use The experts’ editorial went on to discuss the routine clinical use of CSR, which they said would depend on the availability of longer-term follow-up data. “Although other studies have observed a similar mortality rate for patients with refractory angina implanted with CSR and for those with stable angina, such results need to be confirmed by randomized, controlled trials. “Additionally, the value of CSR should also be investigated more extensively in patients with a lower ischemic burden.” They concluded that the clinical evidence looking into CMR had gained “credibility and strength,” due to the different CMR studies that showed a positive redistribution of flow in favor of ischemic territories. “Whether this eventually translates into better quantifiable long-term outcomes remains to be confirmed,” concluded the experts. “Still, CSR is paving the way for treatment options that might not simply prove palliative for patients with refractory angina, offering potentially a new treatment option for such patients.” Study methodology ORBITA-COSMIC is a randomized, double-blind, placebo-controlled trial of the CSR conducted at 6 UK hospitals. In total, 51 patients were randomized, of whom 44 (86%) were male and seven (14%) were female. They were assigned to either the CSR group (n=25) or the placebo group (n=26). Patients had angina, ischemia, and coronary artery disease, with no further antianginal medication and intervention options. They underwent quantitative stress perfusion cardiac MRI (CMR) and recorded angina daily on a smartphone symptom application (ORBITA app) throughout the trial. Treadmill exercise testing, symptom questionnaires and Canadian Cardiovascular Society (CCS) class were assessed. Patients were sedated and then randomized 1:1 to CSR or a placebo procedure. Follow-up CMR, treadmill exercise testing, and symptom assessment were repeated at 6 months. Blinding fidelity was measured. The primary outcome was myocardial blood flow in segments designated ischemic at enrollment during the adenosine-stress perfusion cardiac magnetic resonance scan. The primary symptom outcome was the number of daily angina episodes. Sources: Foley M,J Rajkumar CA, Ahmed-Jushuf F, et al. Coronary sinus reducer for the treatment of refractory angina: (ORBITA-COSMIC): a randomised, placebo-controlled trial. Lancet. 2024 Apr 8 (Article in press). Monti CB, Palmisano A. Coronary sinus reducer: A new hope for refractory angina? Lancet. 2024 Apr 8 (Article in press). Photo Credit: Jason Wermers/CRTonline.org Photo Caption: Michael Foley MD, MBBS, presents findings from the ORBITA-COSMIC trial Monday at ACC.24 in Atlanta.