A new study outlines the substantial improvements in quality of life, symptom severity and exercise capacity among patients implanted with the Coronary Sinus (CS) Reducer in treating patients with refractory angina. The REDUCER-I study found that after six months, almost 70% of patients experienced at least a one-class improvement in their Canadian Cardiovascular Society, (CCS) angina classification, with a significant number moving from severe (Class III or IV) to milder symptom classes. These improvements remained consistent over the following 3 years, indicating lasting symptom relief. “The proposed mechanism of action of the Reducer is that narrowing of the CS causes an increase in backward venous pressure, which creates microvasculature dilatation and a reduction of subendocardial microvascular resistance,” said the authors of the paper published in JACC: Cardiovascular Interventions on Wednesday, led by Dr Stefan Verheye MD, Ph.D. from the Antwerp Cardiovascular Center in Belgium. Main findings More detailed findings of the Shockwave Medical-sponsored study, which was published in JACC: Cardiovascular Interventions, revealed that the major adverse cardiac event rate was 1.6% (95% confidence interval [CI]: 0.7-3.6) and the serious adverse event rate was 1.1% (4/371) with no deaths within 30 days. At 6 months, 69.8% (240/344) of patients improved by ≥1 CCS class. Six-minute walk distances improved by 34.1±85.8m at 6 months (P<0.0001). Interim 3-year results showed CCS class and Seattle Angina Questionnaire quality of life improvements were sustained (P<0.0001). The study also underscored the CS Reducer's strong safety profile. Major adverse cardiac events and device-related complications within 30 days of implantation occurred in only 1.6% of patients, and no deaths were reported during this period. “Other improvements in ischemic burden, myocardial perfusion reserve index, and coronary flow reserve after Reducer implantation have also been reported in studies including imaging and invasive physiology,” said the paper’s authors. Long-term efficacy Commenting on the study’s implications in an accompanying editorial, Giuseppe Andò, MD, PhD, from the University of Messina in Italy and Rocco Antonio Montone, MD, PhD, from the Catholic University of the Sacred Heart in Rome, Italy, said the findings were, “highly anticipated.” Focusing on the long-term efficacy of the CSR, the commentators highlighted that interim 3-year follow-up results in about 200 patients showed that increased exercise capacity and QoL accompanied the sustained and durable alleviation of angina. In addition, severe symptoms were experienced by only 15% of patients at 2 years and 11% at 3 years. The commentators then said that the REDUCER-I study included patients with refractory angina despite nonobstructive CAD. This meant that the patients were identified as having angina and nonobstructive CAD (ANOCA) or ischemia and nonobstructive CAD (INOCA), an emerging subset of patients requiring further pathophysiological investigation to define various endotypes. “We underscore the need for a dedicated subgroup analysis to report outcomes in these patients with ANOCA or INOCA,” they wrote. Microcirculation enhancement The commentary went on to point out that early data in patients with obstructive CAD suggested that the CSR was associated with significant enhancements in microcirculation indexes. However, the experts added that whether the findings can be translated to ANOCA and INOCA needed to be evaluated in studies to also address specific endotypes benefits.“Outcomes such as angina class, exercise tolerance and QoL are based on patient self-report and interviews, which are inherently subject to bias, particularly given the unblinded assessment of symptoms by investigators,” they said. “In this context, the incorporation of modern instruments, such as dedicated smartphone symptom applications, is highly encouraged. These tools can provide more objective and contemporaneous documentation of symptom severity, offering a more reliable and detailed assessment.” Study approach From 2016 to 2023, 400 patients were enrolled, including 78.0% (312/400) male patients, 54.3% (216/398) with previous myocardial infarction, 73.6% (293/398) with previous revascularization, and 72.0% (280/389) CCS class III/IV. The primary effectiveness endpoint was an improvement in CCS class at 6 months. The primary safety endpoints were major adverse cardiac events and device- or procedure-related serious adverse events through 30 days. Study follow-up is planned through 5 years with some interim 3-year analyses included here. Sources: Verheye S, van de Hoef TP, de Silva R, et al. Coronary Sinus Narrowing for Treating Refractory Angina: REDUCER-I Multicenter “Real-World” Observational Study Primary Endpoint Analysis. JACC Cardiovasc Interv. 2024 Nov 6. [Article in Press]. Andò G, Montone RA. Alleviating Refractory Angina Through Coronary Sinus Narrowing Consistent Benefits and the Pursuit of Mechanistic Insights. JACC Cardiovasc Interv. 2024 Nov 6. [Article in Press]. Image Credit: Boonterm – stock.adobe.com