SAN FRANCISCO — In the first head-to-head trials for novel transcatheter aortic valve replacement (TAVR) devices, Acurate Neo flopped and Portico had mixed results, researchers reported at a late-breaking clinical trial session here at the Transcatheter Cardiovascular Therapeutics meeting.
Comparative trials like this are unusual in TAVR, noted press conference moderator Ajay Kirtane, MD, of Columbia University Medical Center/NewYork-Presbyterian Hospital in New York City.
Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai in New York City, had highlighted these trials for that reason. “I’m excited about these valve versus valve studies. I think it is important for us to see which one is best for our patients,” she said.
Many on the discussion panel at the press conference noted how difficult it will be for new devices against the “really mature third-generation devices that are already approved and very effective,” as Robert Bonow, MD, of Northwestern University in Chicago and past president of the American Heart Association, put it.
“It’s an incredibly high bar to meet for any new device…. Device comparisons are going to be harder and harder as we go on in the future,” said Michael Mack, MD, of Baylor Scott & White’s The Heart Hospital in Plano, Texas. “Maybe this is sending the message to the regulators and clinical community, we’re not ready for OPCs [objective performance criteria] yet,” speaking of the less burdensome pathway to approval used for surgical valves.
In the SCOPE I trial pitting the self-expanding Acurate Neo valve against balloon-expandable Sapien 3, the new device missed non-inferiority by a wide margin, with a 30-day rate of the composite safety and efficacy endpoint — all reflecting adverse outcomes — that was 7.1 percentage points higher, and an upper bound to the 95% confidence interval of 12.0 points.
The rate of all-cause death, stroke, life-threatening or disabling bleeding, major vascular complications, coronary artery obstruction requiring intervention, stage 2 or 3 acute kidney injury, rehospitalization for valve-related symptoms or heart failure, repeat procedure for valve dysfunction, moderate or severe valve regurgitation, or valve stenosis was 24% with Neo versus 16% with Sapien 3.
The difference was driven by moderate or severe prosthetic aortic regurgitation (34 vs 10 cases among the 739 enrolled patients, 9% vs 3%), and acute kidney injury was more common with Acurate Neo, too (11 vs three cases, 3% vs 1%), reported Jonas Lanz, MD, of Bern University Hospital in Switzerland.
The trial randomized patients ages 75 and older with symptomatic severe aortic stenosis who were at elevated surgical risk to get transfemoral TAVR with one of the two devices at tertiary heart valve centres in Germany, the Netherlands, Switzerland, and the U.K.
These findings “challenge the generalisability of landmark strategy trials (TAVR vs surgical aortic valve replacement) to all available devices,” the researchers wrote in a paper simultaneously released online in The Lancet.
But it remains to be seen whether these differences translate to clinical outcome differences at 1 year and beyond, and how the device stacks up against CoreValve in the ongoing SCOPE II trial, Lanz told MedPage Today at the press conference.
“It would be hard to sort of make a clinical case, forget the regulatory case, for saying let’s use this if it performed the way it did relative to another choice,” Kirtane said.
In the pivotal PORTICO trial, the self-expanding Portico valve met prespecified noninferiority criteria for safety with a 13.8% rate compared with 9.6% with commercially-available valves (multiple generations of Sapien and CoreValve) for the composite of all-cause mortality, disabling stroke, major vascular complications, life-threatening bleeding requiring transfusion, and acute kidney injury requiring dialysis at 30 days.
The numerical difference in safety parameters was driven by more major vascular complications with Portico (9.6% vs 6.3%), reported Gregory Fontana, MD, of Los Robles Regional Medical Center in Thousand Oaks, California.
The effectiveness endpoint likewise came out noninferior for Portico, with a 14.9% rate of all-cause mortality or disabling stroke at 1 year compared with 13.4% with commercial valves.
Paravalvular leak of at least moderate severity occurred in 6.3% of the Portico group at 30 days compared with 3.1% in the other group.
A post-hoc analysis in the second half of enrollment in the trial showed improvement on several counts, bringing the differential in the safety endpoint to just 0.1% between arms and raising the effectiveness to be 1 percentage point higher with Portico, suggesting a learning curve.
An additional 100 patients enrolled after the 750 in the pivotal randomized portion of the trial when the second-generation delivery system became available showed no deaths or disabling strokes at 30 days. New pacemaker implantation dropped from 27.7% (vs 11.6% in the commercially-available TAVR arm) to 14.6% at 30 days. Major vascular complications declined to 7.0%.
While moderate or greater paravalvular leak remained at 6.5%, Fontana noted that real-world use data from Europe has recently shown it was reduced even with the current generation valve. A second-generation device is in the works.
“I think this study shows that this valve pretty much falls in line with what we have available to us right now. I don’t see any major glaring concerns or difference in terms of how we practice today,” commented Pinak Shah, MD, of Brigham and Women’s Hospital in Boston, a member of the discussion panel at the press conference. “I certainly see evidence of a learning curve, which is true for almost every device we go with in the cath lab.”
“My sense of this device is that presumably it will be another valve we will have available to us in the United States,” he added. “The challenge for all of us is to figure out exactly where it fits in our armamentarium. Is it going to be worth individuals to learn a whole new device when, at least at this point, it’s hard to say there is a major difference compared to the other self-expanding device we have available to us.”
SCOPE I was funded by Boston Scientific.
Lanz disclosed no relevant relationships with industry.
PORTICO was funded by Abbott Medical Devices.
Fontana disclosed relationships with Abbott, Medtronic, and LivaNova.