TCT 2019: Boston Scientific slides on Acurate Neo TMVR trial miss

The Acurate Neo replacement heart valve being developed by Boston Scientific (NYSE:BSX) failed to show non-inferiority in a head-to-head comparison with the Sapien 3 valve made by Edwards Lifesciences (NYSE:EW), according to study data released at the annual Transcatheter Cardiovascular Technologies conference in San Francisco.

The 739-patient Scope I study randomized increased-risk patients to either Acurate Neo or Sapien 3 transcatheter aortic valve replacement, with a primary endpoint of non-inferiority measured by a composite of safety and efficacy at 30 days.

The Acurate Neo cohort met the endpoint in 23.7% of patients, compared with 16.5% for the Sapien 3 group, failing to show non-inferiority. The main differences were higher rates of moderate or severe paravalvular regurgitation and acute kidney injury with the Boston Scientific device, according to the Cardiovascular Research Foundation.

“It would be hard to make the clinical case, forget the regulatory case, for stating, ‘Let’s use [Acurate Neo] if it performed like this relative to another choice,’” said Dr. Ajay Kirtane, of the NewYork-Presbyterian/Columbia University Irving Medical Center, according to TCTMD.

“To me it looks a bit like déjà vu, because we’ve seen this with the earlier valves and the development over time took care of these shortcomings,” added Dr. Jeroen Bax of Holland’s Leiden University Medical Center. “I think if we understand a little bit better the potential anatomical features that are related to [the SCOPE I findings], then you can work with technological developments and move forward.”

BSX shares, which closed down -4.8% at $40.31 Sept. 27, were up slightly at $40.71 today in early trading. EW shares, which closed off -1.9% at $217.29 each last week, were up 0.7% to $218.87.

Boston’s Lotus non-inferior to Medtronic’s CoreValve
A study comparing another Boston valve, the Lotus TAVR, with the Medtronic (NYSE:MDT) CoreValve in high/extreme-risk patients, the Lotus valve met the primary 30-day safety endpoint and was superior on the primary effectiveness endpoint at one year.

The Reprise III trial randomized 912 patients to Lotus or CoreValve at a 2:1 ratio. Three years into the five-year study, the rates of all-cause mortality or disabling stroke (32.4% for Lotus and 36.6% for CoreValve) were similar for both devices. Although the rate of disabling stroke was higher with CoreValve (5.6% for Lotus, 10.5% for CoreValve), more patients in the Lotus arm (44.2%, 29.4%) ended up needing a pacemaker.

“This three-year analysis from the Reprise study demonstrates durability of benefit after Lotus valve implantation. Patients in both cohorts showed a significant improvement in functional and health status, which were preserved over 3 years of follow-up,” according to the study’s abstract.

Edwards’ Sapien XT beats surgery at five years
Five-year results from the Partner 2A trial of Edwards’ older Sapien XT in intermediate-risk patients showed similar rates of death and disabling stroke compared with surgical valve replacement, although one TAVR implantation technique showed poorer outcomes compared with surgery.

The 2,032-patient study randomized to either TAVR or surgery, with a two-year primary endpoint of all-cause death or disabling stroke. At five years, event rates for the primary endpoint were 47.9% for TAVR and 43.4% for the surgical cohort.

Although the transfemoral group showed no difference at five years (44.5% TAVR vs. 42.0% surgical), the transthoracic TAVR group showed a significantly higher rate of death or disabling stroke (59.3% versus 48.3%). Early improvements in functional status and quality of life held steady through five years for both arms.

“In the longest follow-up for intermediate-risk patients with severe AS, TAVR and SAVR had similar rates of death or disabling stroke,” Dr. Vinod Thourani, of the Medstar Heart & Vascular Institute, said in prepared remarks. “Therefore, TAVR should be considered as an alternative to surgery in intermediate-risk patients with severe aortic stenosis. However, in patients without acceptable transfemoral access, surgery may be the preferred alternative.”

Discussion at the conference focused on paravalvular leakage, TCTMD reported.

“When this trial was ongoing, we didn’t have an appreciation that leaving these patients with paravalvular leaks, large leaks, was actually going to be bad for them. That’s what we’ve learned actually from the Partner trials, that leaving them with a lot of leaks is a bad thing,” Dr. Dharam Kumbhani, of the UT Southwestern Medical Center in Dallas, told the website. Newer valves have much lower rates of paravalvular leak, Kumbhani added.
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Sub-study shows QoL benefits for Sapien 3
A sub-study using data from the Partner 3 trial of Edwards’ Sapien 3 valve showed higher quality-of-life scores at one year for low-risk patients.

The sub-study, using data from the 1,000-patient Partner 3 trial of Kansas City Cardiomyopathy Questionnaire scores at one year, showed mean baseline KCCQ scores of 70 on the 0-100-point scale for both TAVR and surgical patients. The benefit persisted at the six- and 12-month marks, albeit at smaller magnitude after a year.

“[E]ven in the low-risk population, there is a huge value from a patient-reported-outcomes standpoint with [TAVR],” said Dr. Suzanne Baron, of the Lahey Hospital & Medical Center in Burlington, Mass., according to TCTMD.

“[P]atient-reported outcomes are incredibly important,” Baron said. “I’ve got plenty of patients who say, ‘I don’t mind if I die, but please, I do not want a stroke because I do not want to live like that.’ … A lot of these patients want to get back to what they’re doing – they want to be able to interact with their families – and in the low-risk populations it’s even more important. A lot of these patients may still be working and caring for grandkids or elderly parents. It becomes a lot more of an issue.”
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Abbott’s Portico non-inferior to contemporary TAVRs
The Abbott (NYSE:ABT) Portico valve, which was tabled for about a year back in 2014 to 2015, showed non-inferiority in a study comparing it to a roster of contemporary TAVR devices in high- or extreme-risk patients.

The 750-patient Portico trial randomized patients 1:1 to either the Abbott valve or then-commercially available devices, including iterations of Medtronic’s CoreValve and Edwards’ Sapien. The primary safety endpoint, a composite of all-cause mortality, disabling stroke, life-threatening bleeds, acute kidney injury requiring dialysis or major vascular complications. Portico showed a 13.8% rate compared with 9.6% for the control devices. Portico met the primary effectiveness endpoint (a composite of all-cause mortality or disabling stroke at one year) at 14.9% compared with 13.4% for the control.

A sub-set of 100 patients implanted using the FlexNav delivery system also met its endpoint, major vascular complications at 30 days. The FlexNav group showed no deaths or strokes, low rates of major vascular complications (7.0%) and pacemaker implants (14.6%) and safety profile similar to the control group at 8.0% and 9.6%, respectively.
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New Mitraclip data on outcomes, cost-effectiveness
Three-year data from the Coapt trial of Abbott’s Mitraclip mitral valve repair device continued to show its benefits, both in terms of outcomes and cost-effectiveness.

The rate of death/heart failure hospitalization in patients treated with Mitraclip was 58.8%, compared with 88.1% for patients treated with guideline-directed medical therapy. And of the 58 patients who crossed over to Mitraclip, the 12-month rate was 28%.

“GDMT- only patients who crossed over and received a MitraClip experienced fewer HF hospitalizations and deaths or heart failure hospitalizations within 12 months than those who did not cross over, with rates comparable to patients originally assigned to the MitraClip,” said Dr. Michael Mack, of the Baylor Scott & White Heart Hospital in Plano, Texas, according to TCTMD. “A significant number of patients died before they had the opportunity to cross over, so there, in all likelihood, is some selection bias both in terms of survivorship and the decision on the local heart team as to having these patients crossed over.”

A separate analysis of Coapt data showed that Mitraclip is comparable to other device-based heart failure treatments in terms of cost effectiveness such as implantable cardiac defibrillators and left-ventricular assist devices.

Follow-up costs were substantially lower for Mitraclip patients, compared with GDMT patients ($26,654 vs. $38,345). But the overall cost at two years was still much higher for Mitraclip, at $73,416 compared with $38,345, due to the higher up-front cost of the initial procedure. Measured in terms of incremental cost effectiveness ratio, Mitraclip was deemed “intermediate value.”

“The cost-effectiveness of TMVr for the COAPT population is comparable to that of other commonly used technologies for the treatment of heart failure, including implantable cardiac defibrillators, and is substantially more cost-effective than the use of continuous-flow left ventricular assist devices for destination therapy,” added Dr. Suzanne Baron, of the Lahey Hospital & Medical Center in Burlington, Mass. “Together with the improved clinical outcomes in the COAPT trial, these findings suggest that TMVr is a reasonable treatment strategy for this patient population based on both clinical and economic considerations.”
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