Real-world results suggest narrowing the coronary sinus with the Reducer (Neovasc) stent may provide durable relief for patients with refractory angina unsuitable for further revascularization.
The balloon-expandable, hourglass-shaped stent was implanted without any device-related events in 50 patients. Significant improvements in angina symptoms, quality of life, and exercise tolerance were present at 4 months and maintained over 12-month follow-up in the single-center study, published in the April 23 issue of JACC: Cardiovascular Interventions.
Controlled narrowing of the coronary sinus lumen occurs within a few weeks of Reducer implantation, ultimately leading to an increase in coronary venous pressure, capillary and arteriolar dilation, lower flow resistance, and restoration of the normal endocardial/epicardial blood flow ratio, according to the authors, led by Francesco Giannini, MD, from the IRCCS San Raffaele Scientific Institute, Milan, Italy.
“We have to consider that besides conventional reperfusion techniques and optimized medical therapy, a proportion of patients are deemed to remain symptomatic for angina,” Giannini told theheart.org | Medscape Cardiology in an email. “Other nonpharmacological treatments currently available only proved partially effective at addressing this cohort of patients, leaving a good proportion of cases unresolved. The Reducer device provides an additional effective option for these patients.”
The device is available in Europe and the Middle East but remains investigational in the United States. In November 2017, Neovasc received US Food and Drug Administration approval to initiate the COSIRA-II IDE trial, intended to support a path toward US approval of the Reducer stent.
In December 2017, however, Neovasc closed its contract manufacturing and consulting services and last month reported a 43% decline in revenues for the year ended December 31, 2017, according to a company news release.
“At this time, I do not have a definitive start date,” for COSIRA-II, Vicki Bebeau, Neovasc vice president of clinical and regulatory affairs, told theheart.org | Medscape Cardiology via email.
In the phase 2 COSIRA trial, patients treated with the Reducer vs a sham procedure were more likely to achieve the primary endpoint of at least a 2-class improvement in Canadian Cardiovascular Society (CCS) angina class at 6 months (18 vs 8 patients; P = .02).
Sustained Benefits
In the present study, 80% of patients improved by at least 1 CCS class following Reducer implantation (20 patients by 1 class, 16 by 2 classes, and 4 by 3 classes). CCS angina class was reduced from a mean of 2.98 at baseline to 1.67 at 4 months (P < .001), with no significant change in CCS class at 1 year (1.64 vs 1.72; P = .351).
Also at 4 months, mean NYHA functional class declined from 1.69 to 1.35, median dyspnea severity Borg Scale scores fell from 4.5 to 1, and 6-minute walk distances increased from 287.0 to 388.6 meters. All Seattle Angina Questionnaire components (physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life) improved, and 32% of patients were able to stop taking at least one antianginal drug.
Benefits were maintained at 1-year follow-up. Recurrent angina with evidence of coronary disease progression occurred in one patient; no cardiac deaths were reported.
Miles Behan, DM, Edinburgh Heart Center, United Kingdom, who coauthored a related editorial, said in an interview that the study population represents only a small portion of those with angina, but one in great need of alternative therapies.
“Sometimes these patients will have walked out of the consulting room hearing the words, ‘There is no more that can be done for you,’ and now this is something that can be done for them and now there is good evidence for it,” he said.
Behan, who has used the device in practice, cautioned that patients need to be “worked up properly with stress echo or a myocardial perfusion scan” because “this thing only works if you have demonstrable myocardial ischemia in the LAD [left anterior descending] territory.”
Of the 76 patients referred for Reducer evaluation, 4 patients were ineligible because of ischemia only in the right coronary artery territory. Another 36 patients went directly to implantation; 7 were treated with further medical therapy optimization and 8 with percutaneous coronary intervention before implantation. One Reducer procedure was aborted because of right arterial pressure greater than 15 mm Hg.
Procedural Steps
Total procedure time and mean iodine contrast volume did not differ significantly between the first and last 25 patients, though fluoroscopy time was cut from 21.8 to 13.7 minutes (P = .034), suggesting a learning curve with regard to coronary sinus ostia engagement, the authors note.
Procedural steps deserving special attention include “careful coronary sinus sizing and implant site evaluation, balancing the need of firmly anchoring the device against the need of delivering the Reducer system as proximal as possible to maximize its effects on the whole ischemic myocardium,” Giannini said.
He also recommends a 20% oversizing of the device to ensure optimal anchoring to the coronary sinus walls, use of a stiffer guidewire to provide maximal support, and advancing the delivery catheter against the neck of the Reducer to guarantee device stability and prevent dislocation. In seven cases with challenging coronary sinus anatomy, device delivery was achieved with the mother-and-child and Josephson catheter techniques.
Commenting for theheart.org | Medscape Cardiology, Christopher B Granger, MD, Duke Clinical Research Institute, Durham, North Carolina, said the subset of patients with chronic, refractory angina represents only about 1% to 5% of all those with angina. Still, the observational data reinforce the potential benefit of the device and “provide important new information that the procedure is feasible and safe in general practice.”
“So it does make me more enthusiastic about the role of the procedure in practice, but I still wish we had a larger trial to better define the degree of benefit and which patients may get particular benefit,” he said.
Who Are the Responders?
Despite patient selection, about 20% of patients in COSIRA and several other observational studies do not have a benefit after Reducer implantation, but this is hard to predict, Giannini said. A recent report by the researchers, however, suggests failure to achieve high wedge pressures during occlusive balloon inflation in the coronary sinus seems to be correlated with poorer or absent clinical response.
“This may be attributed to tributaries of the coronary sinus opening downstream of the device implantation site,” he said. “They are thought to work as anatomical bypass against the increased venous pressure normally achieved with the Reducer device, minimizing its effect. Again, numbers are still too small to achieve significance, and at present day this remains a simple speculation.”
Behan and fellow editorialist William Wijns, MD, PhD, National University of Ireland, Galway, suggest that given the study design, a placebo effect is likely to have contributed in part to the improved outcomes, as also seen in the sham control group of the COSIRA trial.
Nevertheless, they conclude that the “Reducer stent should be considered in patients with refractory angina and demonstrated ischemia in the left anterior descending territory that is resistant to intensive therapy, after having exhausted all options for mechanical revascularization.”
Granger agreed that some of the improvement may be from a placebo effect but said the Reducer appears to have some real benefit.
Asked whether he would use the stent in his own practice if available, he artfully replied, “I would certainly be enthusiastic to have my patients in a randomized trial further evaluating the device because I think it’s promising.”
In more positive financial news, the Reducer stent was recently upgraded to NUB status 1 in Germany, allowing hospitals there to negotiate reimbursement coverage. Neovasc also picked up $7.1 million in proceeds from investor-initiated exercises of Series C warrants, which is sufficient to fund the company until approximately early 2019, according to its April 11 news release.
Giannini is a consultant for Neovasc. All other authors report having no relevant relationships. Wijns has received institutional research grants from stent manufacturing companies and speaker fees from Abbott Vascular, Biotronik, MiCell, and MicroPort; is cofounder of Argonauts; and is a past board member of Cardio3 BioSciences, now Celyad. Behan has received consultancy and speaker fees from Neovasc, Biosensors, and Medtronic.
JACC Cardiovasc Interv. 2018;11:784-792, 793-794. Abstract, Editorial
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