SAN FRANCISCO — In a head-to-head comparison, the self-expandable Acurate Neo (Boston Scientific) valve failed to meet noninferiority for its primary endpoint at 30 days against the balloon-expandable SAPIEN 3 (Edwards Lifesciences) valve.
Moreover, secondary analyses showed the workhorse SAPIEN to be superior for the composite safety and efficacy endpoint, driven by less stage 2 or 3 acute kidney injury (AKI) and less paravalvular leak. Valve dysfunction requiring repeat interventions was also less common at 30 days.
The disappointing SCOPE I results, reported here at the Transcatheter Cardiovascular Therapeutics (TCT) 2019 Conference and published simultaneously in The Lancet, prompted a series of tweets expressing surprise but also dampened some enthusiasm for the Acurate Neo device, which earned CE marking in Europe in 2014 but remains investigational in the United States.
"It would be hard to make the clinical case, forget the regulatory case, for stating, Let's use this when it performed the way it did relative to another device," Ajay Kirtane, MD, New York-Presbyterian/Columbia University Irving Medical Center, New York City, remarked at a press conference.
Michael Mack, MD, Baylor Scott & White Health in Dallas, Texas, pointed out that while AKI and paravalvular leak were more common, not all of the components of the primary endpoint went in the same direction.
"I think this speaks to the fact of how high the bar is, how good the procedure is, how good the devices are, and it's an incredibly high bar to meet for any new device," he said.
SCOPE I is the first randomized trial to compare the two devices in patients with severe aortic stenosis, although Acurate Neo is associated with favorable findings in nonrandomized studies, noted study author Jonas Lanz, MD, Bern University Hospital, Switzerland.
The Acurate Neo device allows top-down deployment and anchoring of the nitinol valve in a supra-annular position, whereas with the SAPIEN 3, both the struts of the stent and the valve are anchored in the annulus.
Asked why they didn't pit Acurate Neo against a self-expanding Medtronic valve, Lanz said they specifically wanted to compare the concepts of balloon-expandable and self-expanding devices and that Acurate Neo and SAPIEN actually share some similarities, such as preserving access to the coronaries. "So there's some overlap in the target populations."
In addition, results are expected next year from SCOPE-II comparing Acurate Neo with Medtronic's self-expanding Evolut R system in 796 older high-risk adults with severe aortic stenosis.
SCOPE I Specifics
For the present study, the investigators at 20 European sites randomly assigned 739 patients, aged at least 75 years, to transfemoral access transcatheter aortic valve replacement with the Acurate Neo or SAPIEN 3. More than 90% of patients were low to moderate risk, their mean age was 57 years, and mean aortic valve area was 0.7 cm2.
The primary safety and efficacy endpoint was all-cause mortality, stroke, life-threatening or disabling bleeding, major vascular complication, coronary artery obstruction requiring intervention, stage 2 or 3 AKI, rehospitalization for valve-related symptoms or congestive heart failure, moderate or severe prosthetic valve regurgitation, or prosthetic valve stenosis at 30 days.
The procedure time was longer with the Acurate Neo vs the SAPIEN 3 (47 vs 40 minutes; P = .002) and contrast volume was greater (128 mL vs 100 mL; P < .0001). Use of pre- and postdilation was also significantly more common in the Acurate Neo group.
The primary endpoint occurred in 23.7% of patients treated with Acurate Neo and in 16.5% treated with SAPIEN 3, which missed the noninferiority margin of 7.7% (noninferiority P = .42) in the intention-to-treat analysis. In a secondary per protocol analysis, SAPIEN 3 was superior (P = .0325).
Although the trial was not powered for individual clinical endpoints, there was more stage 2 or 3 AKI in the Acurate Neo group than in the SAPIEN 3 group (11 vs 3) and more life-threatening bleeding (14 vs 9), Lanz said.
The Acurate Neo group, however, had lower mean transvalvular gradients (7 mm Hg vs 11 mm Hg) and larger mean effective orifice areas (1.73 cm2 vs 1.47 cm2; P for both < .0001). New pacemaker implantation rates were similar (11.5% vs 10.3%; P = .68), he said.
During the formal presentation, co-moderator Martin Leon, MD, New York-Presbyterian/Columbia University Medical Center, asked whether a learning curve may have contributed to the higher rate of AKI, "which was not trivial [at] 3% vs 0.8%."
Lanz responded that most patients were treated at centers with experienced operators and that the AKI "may go along with the longer procedure times, more contrast, but also may be with the pre-and postdilatation, which were more common with the Acurate Neo."
Technological refinements made to a newer iteration of the valve may address some of the issues, he noted. Post hoc analyses are also planned to examine whether there were differences based on anatomic features, such as calcium distribution, protruding calcium, or landing zone size.
Panelist Jeroen Bax, MD, Leiden University Medical Center, the Netherlands, said, "To me, it looks a bit like a déjà vu because we've seen this with the earlier valves and then development over time took care of these shortcomings. So I think if we understand a little bit better what the potential anatomical features are that relate to this, you can work with technological development and we will move forward."
Leon quickly added, "I completely agree that the issues appear to be solvable, that you should certainly be able to solve the paravalvular leak. I'm impressed that this supra-annular, self-expanding device again shows very good hemodynamics. So I think that's encouraging."
Speaking to theheart.org | Medscape Cardiology, Davide Capodanno, MD, PhD, University of Catania, Italy, said the decision to conduct a head-to-head comparison was valuable and that such trials will be more common going forward. "We have to get used to many aspects of these trials, including the methodology, because they present primary endpoints with a lot of components; they are typically noninferiority with wide noninferiority margins. This is something that we will see more and more of, so the results should be interpreted in that respect."
The trial was funded by a research grant from Symetas SA, now part of Boston Scientific. Lanz declared no relevant conflict of interest.
Transcatheter Cardiovascular Therapeutics (TCT) 2019 Conference. Presented September 27, 2019.
Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, join us on Twitter and Facebook.
Medscape Medical News © 2019 WebMD, LLC
Send comments and news tips to news@medscape.net.
Cite this: SCOPE I: Acurate Neo Takes a Beating Against SAPIEN 3 - Medscape - Sep 28, 2019.
Comments