The Source for Neurovascular News and Education

April 07, 2020

Though periprocedural results look good, there are some questions about its rapid rise when long-term data are absent.

Patients with carotid stenosis at high risk for stroke face a difficult decision. Carotid endarterectomy has for decades been the gold-standard treatment, while the less-invasive carotid stenting has so far failed to live up to its promise. Now a third option, transcarotid artery revascularization (TCAR), has burst onto the scene, melding both surgical and percutaneous elements using techniques and a device currently dominated by a single manufacturer.

TCAR proponents believe this is the innovation long awaited in this space, but for patients and physicians a key barrier remains—despite the appeal of TCAR, there’s very little in the way of long-term data to justify its rapid adoption.

To TCTMD, vascular neurologist James Meschia, MD (Mayo Clinic, Jacksonville, FL), pointed out that indications for carotid endarterectomy have been ironed out over decades of study. When carotid stenting was introduced, it was touted as a less-invasive procedure that would avoid a large scar on the neck and would likely be safer than surgery, particularly for older patients. But the CREST trial, for which Meschia was a principal investigator (PI), showed that older patients tended to do better with endarterectomy than with stenting, which carried a higher-than-expected risk of periprocedural stroke.

TCAR promised to reduce that periprocedural stroke risk by eliminating the need to pass catheters through the aortic arch and cross the lesion to deploy cerebral protection devices. The procedure, which to date can only be performed with the Enroute transcarotid neuroprotection and stent systems (Silk Road Medical), is something of a hybrid between surgery and stenting. Direct access to the carotid artery for stent placement is obtained via a surgical cutdown in the neck. Cerebral protection is provided by a temporary reversal of blood flow within the carotid artery; the blood is then returned to the femoral vein after going through a filter to remove debris.

“Essentially everything that has to be done to deal with the carotid stenosis is done after flow reversal is initiated and that has a significant protective effect,” vascular surgeon Apostolos Tassiopoulos, MD (Renaissance School of Medicine at Stony Brook University, NY), explained to TCTMD.

The Enroute systems were approved by the US Food and Drug Administration in 2015, but the procedure received a boost in September 2016 when the Centers for Medicare & Medicaid Services (CMS) allowed coverage for TCAR under the existing national coverage determination for percutaneous transluminal angioplasty when performed in patients with either symptomatic or asymptomatic carotid stenosis who have a high surgical risk. To be reimbursed, hospitals must participate in an approved investigational study, which for TCAR includes the TCAR Surveillance Project (TSP), part of the Society for Vascular Surgery’s Vascular Quality Initiative, and the CREST-2 Registry.

“The real technological advance is in maturing the technology to institute retrograde blood flow while placing the stent,” Meschia explained. And initial data suggest that periprocedural stroke rates with TCAR may be lower compared with transfemoral stenting and comparable to those seen with endarterectomy.

“My concern is that TCAR has been rapidly adopted by largely the vascular surgical community, although other proceduralists are involved as well, and that it is not—at least initially—being held up to the same standard of evidence to justify its use in certain patient populations.” James Meschia

But patient numbers in TCAR studies remain relatively small, and definitive comparisons with the other carotid interventions don’t yet exist, Meschia said. Nevertheless, studies have shown that TCAR use started increasing dramatically after the CMS decision, with a drop in transfemoral stenting procedures following close behind. In the CREST-2 Registry, TCAR rates have been increasing at a clip of more than 15% per year.

“As a vascular neurologist seeing patients with large-vessel stroke, my concern is that TCAR has been rapidly adopted by largely the vascular surgical community, although other proceduralists are involved as well, and that it is not—at least initially—being held up to the same standard of evidence to justify its use in certain patient populations,” he said.

Beyond that, it’s unknown whether TCAR is superior to contemporary medical therapy, a question the ongoing CREST-2 trial is trying to answer for both endarterectomy and transfemoral stenting, Meschia added.

“It leaves the open question of, in an otherwise relatively low-risk-of-stroke patient population like asymptomatic carotid disease, is it even justified? It may be safer to do than transfemoral stenting, but is it better to do than leaving the patient alone and making sure their vascular risk factors are properly managed?” Meschia asked. “That is not known and it is remarkable how rapidly the technology is being adopted without knowing that.”

What TCAR Brings to the Table

Asked why vascular surgeons have been so quick to embrace TCAR, which has been shown to carry a higher overall cost versus endarterectomy or transfemoral stenting, Meschia said that a vascular surgeon’s main concern after making the decision to revascularize is to reduce the risk of perioperative complications. “I think it’s been adopted because, quite frankly, it does appear to be low-risk in terms of periprocedural risk in the right patients done by the right, properly trained people,” he said. “They’re less vested in debating whether there’s an absolute risk reduction by doing it in the setting of intensive medical management.”

Tassiopoulos took a similar view. “A lot of us were skeptical in the beginning, as we are with every new technique. But as you see how your patients fare with this procedure and you see the good outcomes that you can achieve, then obviously the desire to perform more of these is there,” he said. He noted that TCAR comes with smaller incisions and less surgical trauma, cranial nerve injury, and postoperative pain compared with endarterectomy. “It really, for some difficult anatomies, can change the complexity of the surgical procedure very favorably.”

Short-term data do indeed indicate that TCAR carries a lower periprocedural stroke risk compared with transfemoral stenting and comparable risk to carotid endarterectomy, although there was some debate about whether rates are all that different between TCAR and stenting at the recent VEITHsymposium 2019 in New York City.

There, neurologist Thomas Brott, MD (Mayo Clinic, Jacksonville), a CREST-2 PI, presented data from the CREST-2 Registry showing low event rates regardless of the type of revascularization procedure. “Basically all of our treatments are so good and the patients do so well that we have very few clinical events to provide rigorous comparisons among the treatments,” Brott said. He concluded that “TCAR looks good. In fact, I’d say it looks excellent. But so do endarterectomy, transfemoral [carotid artery stenting], and intensive medical management.”

“In order to replace a gold standard, you really need to prove that you have an equally beneficial procedure, both short-term and long-term.” Apostolos Tassiopoulos

Vascular surgeon Mahmoud Malas, MD (University of California, San Diego), argued that TCAR does have a lower periprocedural risk compared with transfemoral stenting. He pointed to a study published in early 2019 in the Journal of Vascular Surgery showing that TCAR carried lower rates of in-hospital stroke/TIA (1.9% vs 3.3%) and stroke/TIA/death (2.2% vs 3.8%) and other data demonstrating less hypotension, lower fluoroscopy times and contrast volume, a lower likelihood of a prolonged hospital stay, and increased discharge home in patients treated with TCAR rather than stenting.

“The big picture that I take out of this study is that we have a new transcarotid stenting procedure that persistently shows a better outcome than any transfemoral stenting. Half the risk of stroke and death with TCAR compared to transfemoral stenting,” Malas told TCTMD. “The second important finding is that we continue to see no difference in stroke and death after TCAR compared to endarterectomy.”

When some type of stenting is being considered, transfemoral stenting will still have a role in patients who are not good candidates for TCAR, like those with a heavily calcified common carotid artery or a “landing zone” in the neck that is too short, he said.

“TCAR looks good. In fact, I’d say it looks excellent. But so do endarterectomy, transfemoral [carotid artery stenting], and intensive medical management.” Thomas Brott

Tassiopoulos agreed, saying that eligibility for TCAR also involves assessments of carotid artery depth and neck characteristics; patients with chronic tracheostomy or prior radiation exposure to the neck, for instance, would be considered for transfemoral stenting rather than endarterectomy or TCAR. “There’s definitely a role for transfemoral stenting because not every patient is a candidate for transcarotid artery revascularization. . . . Careful patient selection and expertise with doing all three types of procedures is probably the best way of securing the best patient outcomes,” he suggested.

Tassiopoulos estimated that of all carotid interventions in his practice, the majority—60% to 70%—are still endarterectomies, about 30% are TCARs, and no more than 5% are transfemoral stenting procedures.

Consistent with that breakdown, Malas said that, “in general, TCAR is now becoming the standard of care minimally invasive procedure for stroke prevention in high-risk patients for [carotid endarterectomy].”

Meschia, however, raised some potential concerns. He said acute occlusion with or without arterial dissection can happen, and that some studies evaluating TCAR show results that are not as good outside of the main registries. Also, the safety of temporarily reversing blood flow during TCAR is not a foregone conclusion, he said. “In patients who’ve had minor stroke that you might be considering revascularization, is it even safe to attempt a reversal of flow in a part of the brain that is already suffering from marginal blood flow? Could it possibly worsen the infarct?” he said. “So early use of TCAR after stroke I think is a complete unknown, and I would be concerned about people trying to prevent emboli but causing worsening stroke in the process.”

If TCAR is used too widely by operators with low procedural volumes, Meschia added, “its real-world risk could be quite a bit higher than its current reported risk.”

Early Enthusiasm Meets More Measured Consideration

The tenor of the discussion around TCAR at the VEITHsymposium reflected some skepticism about adopting TCAR as the next great thing. Vascular surgeon Brajesh Lal, MD (University of Maryland School of Medicine, Baltimore), a co-PI of CREST-2 and PI of the CREST-2 Registry, indicated that a more cautious reception may be warranted, considering the fact that the evidence has not yet caught up to the initial enthusiasm. There are biologically sound reasons to expect that TCAR will work as well as or perhaps better than endarterectomy or transfemoral stenting, but proof is still needed, he said.

“What you’re beginning to see now is really a maturation of the thought process, and so I’m not disconcerted by that at all,” Lal told TCTMD. Now that people have had more time to absorb available TCAR data, “they’re becoming a little more cautious and thoughtful, but I don’t think that is out of the ordinary at all. I think that’s the natural expectation, and I’m actually encouraged to see that happen because that tells me people are beginning to think about it rather than just respond to early enthusiasm.”

“What you’re beginning to see now is really a maturation of the thought process.” Brajesh Lal

Lal outlined four main criteria new procedures have to meet to gain widespread acceptance: establishment of safety, willingness of payers like CMS to reimburse for it, proof of effectiveness when compared with existing options, and acceptability to patients. TCAR is currently sitting at the comparative-effectiveness level, he said. “That’s the box that needs to be checked next.”

To that end, the CREST-2 investigators discussed at a December 7 meeting the possibility of adding a third TCAR component to the study, which is actually two separate trials comparing carotid endarterectomy and transfemoral stenting each against intensive medical therapy in patients with asymptomatic carotid stenosis. TCAR has thus far been excluded from the CREST-2 trials, although patients treated with the procedure are being enrolled in the CREST-2 Registry.

“TCAR has presented some interesting challenges as to where to place it. Some could argue that it is a surgical procedure. Others could argue that it is a stenting procedure,” Lal said. “But most all I think are becoming convinced that it is slightly different than the two, so it cannot truly be accommodated into either one of the two currently existing trials within CREST-2.”

Lal offered no concrete details on what the plan is for integrating TCAR into CREST-2. But, he said, “we’re committed to doing that. What shape that’s going to take is still not determined or, let me just say, finalized.”

There is also a plan for a CREST-3 trial that will randomize symptomatic patients to endarterectomy, transfemoral stenting, or TCAR and have a primary endpoint of periprocedural stroke or death plus subsequent ipsilateral stroke out to 4 years. Lal pointed out that for symptomatic patients with carotid stenosis there is clear evidence that revascularization is superior to intensive medical therapy. Investigators have come to a consensus on the protocol for the trial and will be presenting a proposal to the National Institutes of Health for funding. In the most-optimistic scenario, Lal said, enrollment will begin in late 2020.

Additional trials are always helpful, said Malas, a CREST-2 investigator. But he hinted at some reservations with CREST-2 around the types of patients who are being randomized, noting that patients with moderate degrees of stenosis may be overrepresented in the trial since physicians may be treating those with more severe stenoses without randomizing them. That problem would persist if a third TCAR piece of the trial were added, Malas said. “We do need to have good evidence against medical management, but I think it has to be done properly.”

Continuing to develop evidence around TCAR is crucial, and as the literature grows, “I think the data will speak for itself,” Malas said. But considering the cost and time needed to do a trial like CREST-3, the possibility that the studied treatments will be outdated by the time it has concluded, and criticisms of the generalizability of trial findings, the key data might come from registries, he indicated.

“I think the future is registries, because with registries you really get real-world data. It allows all operators to participate and not only the experienced ones, we are able to enroll all patients and not cherry-pick the healthier ones, and we are able to track the patients longitudinally and to have very granular data,” he said. “Finally, we are able to enroll a lot more patients with significant cost reduction.”

Excitement Over a New Tool

Vascular surgeon Grace Wang, MD (Hospital of the University of Pennsylvania, Philadelphia), observed that TCAR has been increasingly embraced by her specialty over the past few years for patients who are not good candidates for carotid endarterectomy, which is still the gold standard for both asymptomatic and symptomatic patients.

“What’s exciting is that vascular surgeons really have an additional instrument in their armamentarium to treat carotid stenosis,” Wang told TCTMD, adding, however, that additional follow-up data will be needed before its place is cemented.

The lingering questions about whether TCAR will truly be a game changer are not necessarily a bad thing considering that it’s still a relatively new procedure, she indicated. “A healthy amount of skepticism is good because we have a really accepted way of treating carotid stenosis—ie, endarterectomy.”

TCAR has gained in popularity rapidly at least in part because physicians can be reimbursed for the procedure by CMS, but also because early results are excellent, Wang said. “Ultimately, the data tells the truth and I believe with longer-term follow-up even the skeptics will come around.”

“What’s exciting is that vascular surgeons really have an additional instrument in their armamentarium to treat carotid stenosis.” Grace Wang

Wang said that in her practice, 90% of carotid interventions are endarterectomies and the remaining 10% are some type of stenting. In the latter group, TCAR has been her preferred modality in patients with appropriate anatomy.

That mix will vary around the country depending on where operators are on the TCAR learning curve, Wang said. “Vascular surgeons really have the ability to perform all three of these procedures, so they really are able to select the best modality for the treatment of a particular patient.”

Future of TCAR

Wang predicted that over the next several years, TCAR will continue to be adopted by vascular surgeons. “I think that it’s earned its place with other carotid stents for sure, and it’s just a matter of getting people trained and comfortable enough to understand that this technology really adds a lot to the carotid stenosis space.”

Tassiopoulos also predicted continued growth in TCAR, although how much the procedure will cut into the endarterectomy and transfemoral stenting volumes depends on the long-term data that are still lacking. “In order to replace a gold standard, you really need to prove that you have an equally beneficial procedure, both short-term and long-term,” he said.

If those additional data continue to look good for TCAR and the results are durable, “then I foresee that carotid interventions will be either split 50/50 between carotid endarterectomy and TCAR, with very few patients requiring transfemoral stenting, or we will have TCAR prevail over carotid endarterectomy as we move forward.”

Lal predicted that the emergence of TCAR will take over parts of both endarterectomy and transfemoral stenting volumes, with the exact effects varying depending on how comfortable operators are with each procedure at each individual site.

“I think that as with most new techniques and technologies, there’s going to be a continuing increase in interest, enthusiasm, and use and then a leveling off at some point, which you’re already beginning to see, until level-one data is available,” Lal said. Disrupting factors—if it is shown that carotid revascularization improves cognitive function, for instance—could alter the landscape of carotid interventions, he added.

Meschia predicted that Silk Road Medical will soon get some competition from other companies because of the enthusiasm with which TCAR has been embraced. That may help to bring down the cost of the procedure relative to the other options.

Over the next few years, Meschia said, it will be crucial to subject the procedure to the types of rigorous studies endarterectomy and transfemoral stenting have gone through. “It’s time to see if it actually improves the public health, and for that there are precedents. It needs to be held to the same evidentiary standard, I believe,” he said. “Right now, unfortunately, we have the sound of one hand clapping because the proper control group or comparison group for TCAR just isn’t there.”

Currently, “TCAR is going through its honeymoon period. I think that people are adopting it and running with it and getting paid for doing it because they’re in registries. I think that ultimately for it to continue to be reimbursed as a procedure, there’s going to have to be some reckoning with proper controls,” Meschia stressed. “If they have a better mousetrap, which they may well have, then we need to know this. It’s too important to leave it as only optional. It may become standard of care, but it cannot become standard of care in my mind if it has not been held to the same standard as everything else.”

This story was originally published by  TCTMD.com on January 2, 2020. 


 

Disclosures

 

  • Malas reports serving as an investigator for numerous carotid intervention trials, including ROADSTER, ROADSTER 2, CREST, and CREST-2. He is a proctor for Silk Road Medical.
  • Lal reports no relevant conflicts of interest. He receives research funding from the National Institutes of Health and US Department of Veterans Affairs.
  • Meschia, Tassiopoulos, and Wang report no relevant conflicts of interest.