Cerebral embolic protection during TAVR did not reduce overall stroke

 So your doctor still has some work to do to prevent strokes after TAVR(transcatheter aortic valve replacement). YOUR DOCTOR'S RESPONSIBILITY to prevent those strokes.

 

Cerebral embolic protection during TAVR did not reduce overall stroke

BOSTON — In PROTECTED TAVR, the largest-ever randomized trial of transcatheter aortic valve replacement, cerebral embolic protection did not decrease incidence of periprocedural stroke.

However, cerebral embolic protection was associated with reduced incidence of disabling stroke, so the results do not necessarily rule out the benefit of cerebral embolic protection in patients undergoing TAVR, Samir R. Kapadia, MD, chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic and professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, said during a press conference at TCT 2022.

Source: Adobe Stock

Samir R. Kapadia

“As a scientific trial, you would say that the primary endpoint was negative,” Kapadia said at the press conference. “However, the disabling strokes are reduced, so it would be the wrong message to say there was no benefit. [We had to state] the conclusion without overstating it or misguiding the readership.”

The researchers randomly assigned 3,000 patients with aortic stenosis to undergo transfemoral TAVR with or without a cerebral embolic protection device (Sentinel, Boston Scientific).

The primary endpoint was stroke within 72 hours of TAVR or before discharge, whichever came first, in the intention-to-treat population. Secondary endpoints included disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the cerebral embolic protection access site and acute kidney injury. All patients were assessed by a neurologist before and after the procedure.

The results were simultaneously published in The New England Journal of Medicine.

Among the patients from the cerebral embolic protection arm in whom an attempt was made, 94.4% had the device successfully deployed, according to the researchers.

The primary endpoint occurred in 2.3% of the cerebral embolic protection group and 2.9% in the control group (difference, –0.6 percentage points; 95% CI, –1.7 to 0.5; P = .3), Kapadia and colleagues found.

Disabling stroke occurred in 0.5% of the cerebral embolic protection group and 1.3% of the control group (difference, –0.8 percentage points; 95% CI, –1.5 to –0.1; P = .02), according to the researchers. The number needed to treat with cerebral embolic protection to prevent one disabling stroke was 125, Kapadia said at the press conference.

The difference in disabling stroke was driven by disabling ischemic stroke, with six occurring in the cerebral embolic protection group and 17 occurring in the control group, Kapadia said.

There were no differences between the groups in death (cerebral embolic protection, 0.5%; controls, 0.3%), stroke/TIA/delirium (cerebral embolic protection, 3.1%; controls, 3.7%) or acute kidney injury (0.5% in both groups), Kapadia and colleagues found.

One patient in the cerebral embolic protection group had a vascular complication at the device access site, according to the researchers.

A cerebral embolic protection device could not be deployed in 5.5% of patients assigned to that group, but a per-protocol analysis of patients who received the assigned treatment did not differ from the intention-to-treat analysis, the researchers reported.

There were no differences in the primary outcome by subgroup except that it significantly favored the cerebral embolic protection group in patients from the U.S. but not in patients from outside the U.S., and the researchers do not have an explanation for why that happened, Kapadia said.

“Stroke remains unpredictable,” Kapadia said at the press conference. “Despite a big effort, we did not identify who is likely to have them.”

Reference:

• Kapadia SR, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2204961.

Presumed Clinical Benefits of TAVR Cerebral Protection Remain Unproven

 So your doctor still has some work to do to prevent strokes after TAVR(transcatheter aortic valve replacement). YOUR DOCTOR'S RESPONSIBILITY to prevent those strokes.

Presumed Clinical Benefits of TAVR Cerebral Protection Remain Unproven

Large trial comes up short in proving a definitive benefit to debris filters

by Nicole Lou, Senior Staff Writer, MedPage Today September 17, 2022

BOSTON -- Cerebral embolic protection (CEP) again came up empty in preventing strokes after transcatheter aortic valve replacement (TAVR) despite safely capturing embolic material dislodged during the procedure, a large randomized trial found.

In the 3,000-person PROTECTED TAVR trial, the sentinel dual-filter system produced no significant reduction in periprocedural strokes compared with control cases without the device (2.3% vs 2.9%, P=0.30), according to Samir Kapadia, MD, of Cleveland Clinic.

Kapadia added that no subgroup seemed to get less strokes from protected TAVR. "Stroke remains unpredictable," he said in a presentation at the Transcatheter Cardiovascular Therapeutics (TCT) meeting hosted by the Cardiovascular Research Foundation. The results were simultaneously published in the New England Journal of Medicine (NEJM).

This might be disappointing for clinicians who had hoped to narrow down CEP candidates based on this trial. It had been thought that by valve anatomy or procedural characteristics, certain patients would at least benefit more than others, commented Robert Cubeddu, MD, of Naples Heart Institute in Florida, at a TCT press conference.

There was some redemption in Sentinel's association with fewer disabling strokes after TAVR (0.5% vs 1.3%, P=0.02), with the number needed to treat to prevent one disabling stroke being 125 patients.

But this is not a definitive finding and will need to be replicated, cautioned John Carroll, MD, of University of Colorado School of Medicine/Anschutz Medical Campus in Aurora, and Jeffrey Saver, MD, of David Geffen School of Medicine at the University of California Los Angeles, in a NEJM editorial.

Otherwise, the trial produced no substantial differences in mortality rates or the combined endpoint of stroke, transient ischemic attack, or delirium. Incidence of acute kidney injury was the same 0.5% between groups.

PROTECTED TAVR comes years after the much smaller SENTINEL trial, in which CEP successfully filtered out histopathologic debris in 99% of patients but failed to significantly reduce new lesion volume in protected brain territories or reduce major adverse cardiac and cerebrovascular events.

Nevertheless, FDA approved the Sentinel in 2017 on the presumption that catching debris before it reaches the brain should theoretically benefit patients undergoing intracardiac procedures. Since approval, however, real-world data continues to show no stroke benefit with the device.

The adoption of CEP has been variable and slow to proliferate. When asked how the new data would affect clinical practice at the press conference, the panelists broke into a few chuckles.

Michael Young, MD, of Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire, said the study "muddies the waters for programs that are more medium-volume. A number needed to treat of 125 is going to be a tough sell for some of those programs to ubiquitously use that for all their patients."

"A lot of it rolls down to cost and we need to be realistic about that," Cubeddu said. "In many [TAVR] programs across the country, the margins of sustainability and cost and revenue are just marginal."

He suggested it would be interesting to see how the Centers for Medicare & Medicaid Services (CMS) interprets the results of PROTECTED TAVR.

The postmarket trial was conducted at 51 centers in North America, Europe, and Australia. Investigators randomized transfemoral TAVR candidates to the procedure with or without CEP.

Neurologic examinations were performed on all the patients at baseline and after TAVR. Routine neuroimaging was not performed to identify covert brain infarction.

Participants averaged age 78.9. There was a greater proportion of women in the protected group (42.0% vs 37.8% of controls), whereas Society of Thoracic Surgeons surgical risk was similar between groups (3.4% vs 3.3%).

The Sentinel was successfully deployed in 94.4% of attempts.

The trial's primary endpoint was stroke within 72 hours after TAVR or before discharge. Carroll and Saver warned that the counting of these events may have been flawed in the study.

"An underdetection of stroke events may have occurred because neurologic assessments were not always performed by experienced neurologists and because a formal structured interview to determine the presence of stroke symptoms was not used. A small amount of overcounting of end-point events may also have occurred owing to the use of a nonstandard approach of classifying asymptomatic covert infarctions as strokes," they wrote.

As for safety, only one patient had a vascular complication at the access site, according to Kapadia.

"The safety of the device and its possible effect on disabling strokes provide a ray of hope, but the concern persists that CEP, approved and marketed on the basis of surrogate outcomes, may not actually provide a clear and incontestable clinical benefit," according to Carroll and Saver.

In any case, PROTECTED TAVR may be a testament to how much TAVR has matured since it was first developed in 2002.

"The fact that the negative results of the study are in part due to the low incidence of stroke events in the control group conveys good news -- stroke frequency without CEP is low in contemporary practice as compared with the early experience with TAVR and is likely due to operator experience, technical refinements to procedural equipment, and the use of TAVR in healthier patients," the editorialists said.

• 

  Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures

PROTECTED TAVR was funded by Boston Scientific.

Kapadia disclosed relationships with Navigate and Admedus.

Carroll disclosed relationships with Edwards LifeSciences and Medtronic. Saver disclosed relationships with, and/or support from, Filterlex, Abbott, Medtronic, Bayer, Roche, Johnson & Johnson, Amgen, MIVI, Rapid Medical, Novo Nordisk, and Edwards.

Cubeddu disclosed no relationships with industry.

Young disclosed a relationship with Medtronic.

Primary Source

New England Journal of Medicine

Source Reference: Kapadia SR, et al "Cerebral embolic protection during transcatheter aortic-valve replacement" New Engl J Med 2022; DOI: 10.1056/NEJMoa2204961.

Secondary Source

New England Journal of Medicine

Source Reference: Carroll JD and Saver JL "Does capturing debris during TAVR prevent strokes?" New Engl J Med 2022; DOI: 10.1056/NEJMe2210185.

Cerebral embolic protection during TAVR reduces disabling stroke but not overall stroke

 So how are your doctors guaranteeing your 100% recovery from that stroke if they can't prevent it? Don't let them weasel out of truthfully answering.

Cerebral embolic protection during TAVR reduces disabling stroke but not overall stroke

BOSTON — In PROTECTED TAVR, the largest-ever randomized trial of transcatheter aortic valve replacement, cerebral embolic protection did not decrease incidence of periprocedural stroke.

However, cerebral embolic protection was associated with reduced incidence of disabling stroke, so the results do not necessarily rule out the benefit of cerebral embolic protection in patients undergoing TAVR, Samir R. Kapadia, MD, chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic and professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, said during a press conference at TCT 2022.

Source: Adobe Stock

Samir R. Kapadia

“As a scientific trial, you would say that the primary endpoint was negative,” Kapadia said at the press conference. “However, the disabling strokes are reduced, so it would be the wrong message to say there was no benefit. [We had to state] the conclusion without overstating it or misguiding the readership.”

The researchers randomly assigned 3,000 patients with aortic stenosis to undergo transfemoral TAVR with or without a cerebral embolic protection device (Sentinel, Boston Scientific).

The primary endpoint was stroke within 72 hours of TAVR or before discharge, whichever came first, in the intention-to-treat population. Secondary endpoints included disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the cerebral embolic protection access site and acute kidney injury. All patients were assessed by a neurologist before and after the procedure.

The results were simultaneously published in The New England Journal of Medicine.

Among the patients from the cerebral embolic protection arm in whom an attempt was made, 94.4% had the device successfully deployed, according to the researchers.

The primary endpoint occurred in 2.3% of the cerebral embolic protection group and 2.9% in the control group (difference, –0.6 percentage points; 95% CI, –1.7 to 0.5; P = .3), Kapadia and colleagues found.

Disabling stroke occurred in 0.5% of the cerebral embolic protection group and 1.3% of the control group (difference, –0.8 percentage points; 95% CI, –1.5 to –0.1; P = .02), according to the researchers. The number needed to treat with cerebral embolic protection to prevent one disabling stroke was 125, Kapadia said at the press conference.

The difference in disabling stroke was driven by disabling ischemic stroke, with six occurring in the cerebral embolic protection group and 17 occurring in the control group, Kapadia said.

There were no differences between the groups in death (cerebral embolic protection, 0.5%; controls, 0.3%), stroke/TIA/delirium (cerebral embolic protection, 3.1%; controls, 3.7%) or acute kidney injury (0.5% in both groups), Kapadia and colleagues found.

One patient in the cerebral embolic protection group had a vascular complication at the device access site, according to the researchers.

A cerebral embolic protection device could not be deployed in 5.5% of patients assigned to that group, but a per-protocol analysis of patients who received the assigned treatment did not differ from the intention-to-treat analysis, the researchers reported.

There were no differences in the primary outcome by subgroup except that it significantly favored the cerebral embolic protection group in patients from the U.S. but not in patients from outside the U.S., and the researchers do not have an explanation for why that happened, Kapadia said.

“Stroke remains unpredictable,” Kapadia said at the press conference. “Despite a big effort, we did not identify who is likely to have them.”

Reference:

• Kapadia SR, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2204961.

CardioBrief: New Stroke Prevention Device Might Not Prevent Strokes

A great stroke association president would have a team validating all research to do with stroke rather than working on the fucking lazy items of press releases, prevention, awareness and F.A.S.T.. But no, we have fucking failures of stroke associations instead, doing nothing useful for survivors.
https://www.medpagetoday.com/Cardiology/CardioBrief/65872?

There's no hard evidence the Sentinel filter reduces stroke in TAVR

• by Larry Husten, CardioBrief June 08, 2017

Here's how to get a second-generation medical product or add-on product approved: Show that the original device isn't nearly as safe and effective as believed back in, you know, the dark ages before the new product showed up.
Until now, proponents of transcatheter aortic valve replacement (TAVR) have sought to emphasize the benefits of TAVR and have downplayed its negative aspects, including stroke. Now, with the clearance of an add-on device for TAVR that may help prevent some strokes, these same TAVR supporters are emphasizing the stroke risk.
Martin Leon (Columbia University), a top TAVR advocate, said in a press release for the new device that "anything we can do as clinicians to reduce the risk of brain injury is extremely meaningful."
On Monday, the FDA cleared the Sentinel Cerebral Protection System, which is designed to reduce the incidence of stroke in the aftermath of a TAVR procedure. In a press release the manufacturer of the device, Claret Medical, said it is "the first and only embolic protection device shown to reduce TAVR procedural strokes by 63%."
But there are a few big problems the company did not exactly highlight in its press release. The device has not been proven effective and, although stroke is certainly a serious complication of TAVR, until now the actual rate of stroke associated with TAVR has been reported to be much lower than the company stated in its press release.
Sentinel therefore joins the growing list of cardiac devices that have been cleared but for which there is no or extremely limited evidence showing that they work. These include the Watchman left atrial appendage closure device, the Absorb bioresorbable stent, the Impella heart pump, patent foramen ovale (PFO) closure devices, and catheters to open chronic totally obstructed arteries.
TAVR and Stroke
The Claret Medical press release exaggerated the significance of stroke in TAVR patients: "Recent studies have found that almost one in 10 patients experience a clinically-apparent stroke due to the procedure." But the source for this statistic is their own clinical trial, in which they went looking for evidence of stroke.
Like a baseball field of dreams, in the field of medical devices if you build it they will come. But outside their own field of dreams, in the real world, the numbers are quite different. As Sanjay Kaul (Cedars-Sinai) observes, the stroke rate is much lower in real life: "The 30-day stroke rate of 9.1% in the control arm appears to be much higher than what is observed with contemporary newer-generation TAVR devices such as SAPIEN 3 (2.7%)." Of course, no one would want to discount stroke as an adverse event, but a rate of one in 10 is a lot worse than a rate of one in 37.
Robert Yeh (Beth Israel Deaconess) said he thinks the high rate is reasonable, although it includes minor strokes that might not be caught in normal clinical practice. He said that the high stroke rate in the control arm was a result of the trial's design, which included detailed stroke assessments. "This is a very sensitive (albeit probably accurate) definition of stroke."
Questions About Effectiveness
More importantly, there's no solid evidence that the device actually reduces the risk of stroke.
In the press release, Leon broadly endorsed the benefits of the device: "The 63 percent reduction in clinical strokes in the first 72 hours after TAVR, combined with the fact that one in four patients had an average of 25 particles of debris collected that were visible to the naked eye, is striking. The device was delivered safely, added minimal time to the procedure, and performed as intended with capture of embolic material and reduction in ischemic brain injury."
But Leon neglected to mention the single most important fact about the trial: It failed to meet its primary effectiveness endpoint. There was no significant difference in the size of new lesions in the brain. Instead, Leon focused exclusively on the secondary or post-hoc endpoints.
A major problem is that the small number of strokes in the trial make it is impossible to draw any firm conclusions about the effectiveness of Sentinel. There were only 23 strokes in the trial, just 3 of which were disabling.
Here are the details: The overall stroke rate was 9.1% in the control group versus 5.6% in the Sentinel group. But this was based on 10 events in 110 patients in the control group versus 13 events in 231 treated patients. These numbers are very small and did not come close to statistical significance (P=0.25). Even worse, the numbers are driven almost entirely by nondisabling strokes. There were 9 nondisabling strokes in 110 control patients versus 11 nondisabling strokes in 231 treated patients. For disabling strokes -- the most important thing you want to prevent -- there were only 3 events, 1 (out of 109) in the control group versus 2 (out of 231) in the treatment group. No difference whatsoever.
'Reasonable People Will Argue'
Given the clinical importance of stroke, the absence of any other available treatment, and the lack of any safety concerns, FDA clearance was not indefensible but not a given either, said two cardiologists who were asked to comment.
Kaul said that "reasonable people will argue" whether the results provide "the 'reasonable assurance' statute for device approvals, even for a Class II device."
Yeh said that clearance of the device "looks fair to me based on biological plausibility, direction of effect of the major endpoints (namely stroke), the fact this is not a long-term therapy or a permanent implant, but just a device that supports another procedure, and the low risk of harm."
Yeh concluded that "1) there probably are a fair amount of minor strokes after TAVR. This is probably true for SAVR [surgical aortic valve replacement] as well. 2) Using a sensitive definition of stroke helps the company. 3) It's probably fair to use the sensitive definition of stroke here since it is considered the gold standard, and also, going full circle, if it were me, I would want to avoid those very minor strokes in addition to the larger clinically obvious ones."
The good news, in my opinion, is that the device appears to be safe. It's unlikely that patients will be directly harmed by the device (except for the added cost, of course), and it is for this reason that the FDA went ahead and cleared the device. But there's a very dangerous and very steep and slippery slope here. Now that the device is on the market it may well be impossible to prove whether or not it is effective. Next-generation devices will only need to prove that they are equivalent to Sentinel. An entire industry could develop based on a safe but ineffective device.
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