New SCOPE Data Put ACURATE neo on the Back Foot Again

ACURATE neo's (Boston Scientific) place in the treatment of severe aortic stenosis is unclear after failing to show noninferiority in a head-to-head comparison with another self-expanding, supra-annular transcatheter valve and reporting lackluster outcomes at 1 year in the SCOPE I trial.

The valve stumbled last year in SCOPE I when it did not establish noninferiority when compared with the balloon-expandable intra-annular Sapien 3 (Edwards Lifesciences) valve at 30 days.

In the SCOPE II trial, the ACURATE neo took on the self-expanding CoreValve Evolut (Medtronic) in 796 older adults (mean age, 83 years; 67.5% women) with symptomatic severe aortic stenosis (STS-PROM score, 4.6%).

The primary endpoint of all-cause death or any stroke at 1 year occurred in 15.8% of ACURATE neo patients and 13.9% of CoreValve patients in an intention-to-treat analysis (one-sided upper 95% confidence limit, 6.1%; P = .0549 for noninferiority).

In a per-protocol analysis, the primary endpoint occurred in 15.3% and 14.3%, respectively (one-sided upper 95% confidence limit 5.4%; P = .0314 for noninferiority).

The study could not claim noninferiority, however, because the protocol required both analyses to show noninferiority at a margin of 6%, explained Corrado Tamburino, MD, PhD, University of Catania, Italy.

The findings were presented in a late-breaking clinical trial session at the virtual meeting of Transcatheter Cardiovascular Therapeutics (TCT) 2020 and published simultaneously in Circulation.

Rates of all-cause mortality and stroke were similar in both groups, although cardiac deaths were significantly higher in the ACURATE neo group in the intention-to-treat (31 vs 14) and per-protocol (39 vs 13; P for both = .01) analyses.

Session co-moderator Martin Leon, MD, NewYork-Presbyterian/Columbia University Irving Medical Center, New York City, said "death events always make us nervous" and pointed out that procedural and intraprocedural deaths were also higher with ACURATE neo, at 8 vs 1. "Can you give us more clarity on the death events that would help us feel less anxious that there really is a mortality difference between these two devices?"

Tamburino said they searched to see if there was a learning curve influence on the rate of events and "there was not, unfortunately. Because all centers — young centers and experienced centers — ­had a similar rate."

He noted that most of the cardiac deaths were sudden deaths or heart failure deaths occurring in patients with mild postprocedure aortic regurgitation, "which we know is linked to paravalvular regurgitation."

Moderate or severe aortic regurgitation was higher in the patients treated with ACURATE neo at 30 days (9.6% vs 2.9%) and 1 year (4.0% vs 3.3%; P for both < .0001).

The ACURATE neo group, however, had significantly fewer new pacemaker implantations at 30 days (10.5% vs. 18.0%) and 1 year (11% vs. 18%) and less left bundle branch block at 1 year (14% vs 19%) in the intention-to-treat cohort.

Head-to-head trials like this are increasingly important, given that transcatheter aortic valve replacement (TAVR) is becoming more of a low-risk procedure in the majority of patients, discussant Bernard Prendergast, MD, Guy's and St Thomas' NHS Foundation Trust, London, England, said. "So these results — standing alongside the existing results of SCOPE I — are very important in establishing this new technology compared with the current market leaders."

He asked why a small but significant number of patients did not receive the intended valve in either arm and observed that echocardiographic follow-up was limited. "If paravalvular aortic regurgitation is an important measurement in this study, that might be a fair criticism of the follow-up."

The main reason for not receiving the assigned valve was because of a size difference, Tamburino said. Of the 386 ACURATE neo patients in whom TAVR was initiated, 377 received the assigned valve, five received the CoreValve, and four got other valves. Of the 388 CoreValve patients in whom TAVR was initiated, 366 got the CoreValve 26 mm or 29 mm, four received the ACURATE neo, and 18 received other valves.

In terms of hemodynamics, the results were similar, including valve gradients, between the ACURATE neo and CoreValve groups, he said. "But there was a very low rate of echocardiography at 1 year (236 ACURATE neo vs 242 CoreValve), so we miss a lot of meaningful information that could explain some of the clinical events at follow-up."

Given that ACURATE neo, which is not approved in the United States, failed to make the primary endpoint in SCOPE I and SCOPE II compared with the gold standard valves, Leon asked: "Do we conclude from this that it's an inferior device or do we conclude it is an early generation device and maybe there are operator experience issues?"

"These trials need to be taken with a grain of salt; people are learning in these trials and these valves are being iterated," discussant Michael Reardon Houston Methodist Hospital, Texas, said. "If you look at the death, that clearly worries us, [but] all these complications that we don't normally associate with death — stroke, bleeding, coronary obstruction, annular rupture — all the same. Pacers and left bundles are better for the ACURATE and what was worse — paravalvular leak.

"Well the new one, neo2, is joining the ranks of the robust sealing skirts and hopefully will be better," he said. "These are all iterations and I think to cut any one off early, would be a disservice to our field."

SCOPE I at 1 Year

Two days later, SCOPE I investigators took to the virtual stage to report on 1-year follow-up available for 96% of patients treated with the ACURATE neo and 97% treated with the Sapien 3.

At 1 year, all-cause death or disabling stroke occurred in 12.5% of the ACURATE neo group and 9.2% in the Sapien 3 group (hazard ratio, 1.28; 95% CI, 0.81 - 2.0).

Although lower rates of paravalvular regurgitation and acute kidney disease with the Sapien 3 drove the primary endpoint at 30 days, there was no difference at 1 year in all-cause or cardiovascular death rates between patients with moderate/severe or mild aortic regurgitation vs no regurgitation.

"So in the end, with this relatively shorter 1-year follow-up, the aortic regurgitation didn't play a role regarding patients' deaths," Thomas Walther, MD, PhD, University Hospital Frankfurt, Germany, said.

Clinical and functional outcomes were similar for the ACURATE neo and Sapien 3 groups, including all-cause death (11.1% vs 8.5%), cardiovascular death (6.9% vs 5.4%), disabling stroke (2.8%% vs 1.7%), need for a permanent pacemaker (11.4% vs 12.0%), and NYHA class III (11.5% vs 14.2%) or class IV (0.7% vs 0.3%).

Patients who received the ACURATE neo had lower mean valve gradients (7.20 mm Hg vs 11.45 mm Hg; P < .001) and higher effective orifice areas (1.76 cm² vs 1.50 cm²; P < .001), but rates of moderate (7.1% vs 3.6%) or severe (1.8% vs 0%) paravalvular regurgitation remained higher at 1 year (P = .006).

"Extended follow-up data will be crucial to determine the impact of the differential valve performance on long-term outcomes," he concluded.

Discussant David J. Cohen, MD, University of Missouri-Kansas City School of Medicine, said it's unlikely this particular valve will get much use in the United States because of the regurgitation.

"I'm hopeful the next-generation device will seal better and get rid of the aortic regurgitation. Then I could see this having a particular role in places where we like to use self-expanding valves, where there's worry about annular rupture from a lot annular calcification or outflow tract calcification," he said. "But we also need coronary access because that's really the difference between this device and other self-expanding devices like the CoreValve. This has very, very nice coronary access due to the very open frame in the supra-annular position."

SCOPE I was funded by Boston Scientific. SCOPE II was sponsored by Ceric Sàrl. Tamburino reported speaker fees from Medtronic. Walther has disclosed no relevant financial relationships.

Circulation. Published online October 15, 2020. Abstract

Transcatheter Cardiovascular Therapeutics (TCT) 2020: SCOPE II, presented October 15, 2020; SCOPE I, presented October 17, 2020.

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