It’s a Swing and a Miss for Boston ScientificIt’s a Swing and a Miss for Boston Scientific
The company’s high-profile TAVR trial missed its primary endpoint. So, what went wrong? MD+DI spoke with the trial's co-principal investigator to find out.
October 31, 2024

Boston Scientific swung and missed the primary endpoint of its ACURATE investigational device exemption trial, the company announced Wednesday at Transcatheter Cardiovascular Therapeutics (TCT) 2024.
The randomized trial evaluated the Acurate neo2 valve in the treatment of patients with severe, symptomatic aortic stenosis at low, intermediate, high, and extreme risk of open-heart surgery. Acurate neo2 is Boston Scientific’s second-generation transcatheter aortic valve replacement (TAVR) technology, which is CE marked in Europe but does not have FDA approval. The IDE trial pitted Acurate neo2 against a pre-defined control valve, either Edwards Lifesciences’ Sapien valve or Medtronic’s Evolut TAVR system, selected at the discretion of the implanting physician.
The company had hoped to show that Acurate neo2 was non-inferior to the commercially available Sapien and Evolut systems (the control arm). To do so, Boston Scientific’s device would have needed to meet the pre-specified criteria for non-inferiority, which was 77.9%. Composite rate of all-cause mortality, stroke, or re-hospitalization at one year was 16.16% in the Acurate neo2 arm and 9.53% in the control arm.
ACURATE miss isn't necessarily a strikeout
"The good news is I have a reason that it didn't make it, and I can show you how to see it, and I can show you how to treat it. So, I think there's a real good case for going forward." — Michael Reardon, MD, professor of cardiothoracic surgery at Houston Methodist DeBakey Heart & Vascular Center and co-principal investigator of the ACURATE IDE trial
MD+DI spoke with Michael Reardon, MD, professor of cardiothoracic surgery at Houston Methodist DeBakey Heart & Vascular Center and co-principal investigator of the ACURATE IDE trial to find out what went wrong and if there is a path forward for the Acurate neo2 valve in the U.S. TAVR market.
A post-hoc analysis identified and evaluated expanded and under-expanded Acurate neo2 valve frames within the trial. The company reviewed key procedural factors, including pre- and post-dilation, which helps to prepare for, enable, and confirm proper valve expansion during the procedure. It turns out that about 20% of the Acurate neo2 valves were under-expanded.
“Under expansion means I didn't expand the valve out as far as it was supposed to go. So, if it doesn't expand out as far as it's supposed to go, it's not going to work normally,” Reardon told MD+DI. “And we know that in the world of endovascular stuff, under expansion is a bad thing.”
He cited the early days of coronary stents when implanting physicians had to learn the hard way that it's critical to image the stent after implantation and ensure that it is expanded fully. With TAVR, when a physician implants either the Sapien or the Evolut valves, they've learned to look for under expansion. In fact, Reardon said, what he does is what's called a right anterior oblique caudal (RAO) projection, which is a specific fluoroscopic view used during the procedure to optimally visualize the aortic valve and its cusps, allowing for accurate placement of the new valve.
"If it's not fully expanded—even if it looks good, no gradient, no leak—we still balloon it," he said. "For my balloon-expandable procedures ... if the cells aren’t fully expanded then I expand it. What we showed was engineering wise, if you put this on a pulse duplicator when it’s fully expanded not only does it have better flow, but it has laminar flow and good neo-sinus washout, washing out at the base of the valve. If you’re under-expanded not only does it have less flow, but you have non-laminar flow and you have less washout, so you have stagnation at the base of that, and that is a very plausible reason for platelets to become activated and clumped and have micro emboli."
So, ensuring that blood can flush through the newly created area in TAVR is crucial to prevent blood stagnation and potential thrombus formation.
The COVID-19 curveball in ACURATE
The COVID-19 pandemic threw more than one curveball at the Acurate trial, however.
"Here you have this brand-new valve that nobody in the U.S. is using, it's just as we start with the first wave of COVID, it takes us four years to finish this, the average time between implants is three months, and there are only three sites that did more than one a month," Reardon said.
Not only did the pandemic present staffing challenges, making it tough for the investigators to get the research personnel they needed, and patient recruitment challenges, but the global supply chain crisis made it tough to get the balloons needed for the procedure. So, even though TAVR cases were still being performed commercially every week with Sapien or Evolut, the research cases with Acurate were fewer and farther between.
“So, to compare a valve that is brand new to you every couple of months to one you’re doing every week, multiple times, that built in a bias,” Reardon told MD+DI.
To add insult to injury, this is the first time in TAVR that an investigational device exemption trial has done an all-risk analysis right off the bat. When Edwards and Medtronic were going through their TAVR trials, they started with patients who were at extreme and high risk for open surgery before studying the valves in the lower risk populations.
"If you look at the original trials we started with high and extreme risk, we learned about the valve, we iterated the valve, and then we applied it to intermediate risk, and then we learned about the valve, we iterated the valve, and we applied it to the low risk [patients]," Reardon said. "Well, here we're asked to do all-risk analysis with no chance to learn or to iterate."
He said if the trial had been done similarly to the original TAVR trials the investigating physicians would have learned enough that they would have known how to look for and treat under-expansion by the time the new valve was being implanted into lower-risk patients.
"The good news is I have a reason that [the ACURATE trial] didn't make it, and I can show you how to see it, and I can show you how to treat it. So, I think there's a real good case for going forward." Reardon said.
Looking ahead to the next inning
"The data presented today give clinicians a greater understanding of the impact of procedural optimization as the TAVR space continues to rapidly evolve," said Janar Sathananthan, MD, chief medical officer of interventional cardiology therapies at Boston Scientific. "We believe the findings from the ACURATE IDE post-hoc analysis and implementation of steps to mitigate valve under-expansion may improve outcomes for the ACURATE valve and have important implications on other commercially available TAVR valves, and we look forward to studying these improved techniques in future trials of the device."
Boston Scientific said it continues to work closely with FDA on the regulatory strategy for approval of the Acurate valve platform in the U.S. Still, it does raise some questions for investors about what comes next for the new TAVR valve.
"It's unclear what this means for FDA approval of Acurate neo2, but we think approval is less likely and some sort of additional clinical data may be required," Mike Matson, a medtech analyst at Needham & Co, wrote in a report Wednesday. "...Since this appears to be a learning curve or training issue, we think it is unlikely to have a significant impact on [the company's] international Acurate neo2 sales which we estimate are >$350M annually."
Other analysts seemed somewhat more optimistic overall, especially after hearing from Boston Scientific management during a late afternoon investor event Wednesday.
"Our immediate reaction is that we think it remains a possibility for [Boston Scientific] to submit the data with post-hoc analysis to the FDA and believe investors are now not counting on any approval or revenue contribution," Marie Thibault, a medtech analyst at BTIG, noted in her TCT report Thursday morning. "We are less worried about commercial impact in Europe because it seems current users are aware of the need for pre- and post-dilation, though we wonder if the headline on non-inferiority may make it harder for [Boston Scientific] to find new adopters. Management reaffirmed its commitment to the TAVR market and the structural heart valves space more broadly with investments in mitral repair, tricuspid repair, and tricuspid replacement."
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