Gains in Carotid Stenting Technology Could Increase the Treatment’s Appeal

HOLLYWOOD, FL—What with no distinct advantage for carotid artery stenting (CAS) over carotid endarterectomy (CEA)—and today’s availability of more aggressive medical therapy—it is unclear which approach to revascularization holds an edge, experts said last week at the International Symposium on Endovascular Therapy (ISET) 2017. But it may be that tweaking certain aspects of CAS devices tips the scales.

Ten-year follow-up from the CREST trial and 5-year follow-up from the ACT I study, presented at last year’s International Stroke Conference, showed that CAS holds up well over the long term against CEA in asymptomatic and symptomatic patients with severe carotid stenosis. CREST-2 is looking into how revascularization fares over medical therapy alone in asymptomatic patients, but it features an unusual, two-arm design that may preclude direct comparisons between stenting and surgery.

“Despite some opinions to the contrary, [CAS] is currently in decline generally for treatment of symptomatic and asymptomatic carotid stenosis,” said vascular surgeon Frank Veith, MD (Cleveland Clinic, OH), in his presentation. “This is because [for] symptomatic carotid stenosis patients, recent randomized trials, population-based studies, and a recent systematic review show much higher stroke and death rates with CAS than [with] CEA.”

Even more instrumental, he said, is the fact that for “most asymptomatic carotid stenosis patients, best medical treatment has such low stroke rates that it may make CAS and CEA unnecessary in many patients that have been done in the past.”

With the use of statins and other drugs, Veith reported, the annual stroke risk of asymptomatic patients has dropped from 3-6% in 1985 to less than 1% in 2017. He cited a 2015 paper in JAMA Neurology confirming that asymptomatic patients on what he termed “good medical treatment” have a less than 0.1% risk of occlusion and 0.9% risk of stroke each year. Additionally, according to a 2016 systematic review in the European Journal of Vascular & Endovascular Surgery, the stroke/death rate of symptomatic patients undergoing carotid stenting exceeded the 6% risk threshold set by the American Heart Association—at which CAS is thought to be an alternative to CEA—in 72% of registries. In 28% of registries, their stroke/death rate exceeded 10%.

‘Outlook of CAS’ Is Bright

“However,” he stressed, “I believe the outlook of CAS is bright because of three advances that are currently on the horizon that may decrease strokes.” These include better embolic protection devices with cessation or reversal of flow (eg, Medtronic’s Mo.Ma device), cervical access to avoid the aortic arch and reverse flow (eg, Silk Road Medical’s ENROUTE system), and membrane or mesh-covered stents to stop delayed strokes, Veith said.

“We all know that delayed strokes after the protection device is out constitute the majority of strokes that occur after CAS,” Veith commented. “These delayed strokes are due to these particulate debris protruding through the stent after the stenting procedure. And as flow is restored, these wash off into the brain and cause delayed strokes.” He highlighted three stents that “have finer pore sizes” to block embolic debris and are now under study: a new mesh-covered stent (WL Gore), CGuard (InspireMD), and Roadsaver (Terumo).

If the aforementioned advances can prove to reduce stroke risk with CAS, Veith said, stenting “would be more competitive to CEA and would replace CEA more widely than it does now.” For asymptomatic patients in particular, he noted, there are some promising ways to pinpoint the minority who are at high risk of actually having a stroke: transcranial Doppler detection of microemboli as well as plaque analysis via duplex, MRI, and CT. Patients selected by these methods “clearly would benefit from CAS or CEA in addition to best medical treatment, thus increasing the number of patients needing CAS and reducing the number of unnecessary procedures,” Veith concluded.

“However, there is one reservation, and that is that the efficacy of these . . . methods for decreasing CAS stroke rates and improving asymptomatic patient selection must be proven by appropriate clinical trials, which are in progress,” he cautioned. In the meantime, Veith advised, it’s important for vascular specialists as a whole to prepare for the possibility of improved CAS outcomes “by being familiar with the procedure.”

Targeting Minor Stroke

William Gray, MD (Main Line Health/Lankenau Heart Institute, Wynnewood, PA), pointed out that in the “highest-quality, level 1 data sets, really carotid stenting and endarterectomy are no different.” Showing CREST results in his presentation, he said, “You see the similar mortality at 4 years. You see the similar freedom from ipsilateral stroke out to 4 years. I mean, these lines are superimposable. It’s a dealer’s choice as to which therapy is going to be effective for the patient.” Moreover, he added, rates of freedom from TVR indicate both procedures offer “very robust durability.”

Minor stroke, though, “is where the nut is. This is where we can potentially really improve carotid stenting,” Gray suggested, citing 30-day numbers from CREST of 3.2% for CAS and 1.5% for surgery (P= 0.0088). “If you think about it mechanistically, the minor stroke excess that we’re seeing in carotid stenting, albeit typically resolving within a few days, still is probably related to [diffusion-weighted MRI] findings, which I suspect are a greater embolic load to the brain.”

[Minor stroke] is where the nut is. This is where we can potentially really improve carotid stenting. William Gray

Timing, location, and mechanism of stroke each may enable the achievement of better carotid stenting outcomes, he said.

“The maximal emboli produced during carotid stenting is actually during poststent balloon inflation,” Gray noted, reporting that for this reason, his cath lab avoids this practice. “We’ll leave 30% lesions behind without any sequelae,” he said. “But if you have to do it, this is where most of the strokes will occur.”

One solution may be the Paladin device (Contego Medical), which provides “integrated embolic protection” consisting of a carotid postdilation balloon and an attached filter with a pore size of 40 µm, Gray said.

As for location, he continued, not all strokes are ipsilateral. CAPTURE registry data showed that around one in five strokes were in fact nonipsilateral, Gray reported. “So how does that happen? It almost certainly happens from the access, when we’re dinking around in the aorta.” Extrapolating that idea to the ipsilateral segment, it’s possible that with CAS “up to 35-40% of all strokes may be coming from the arch access, from transfemoral caths,” he proposed.

Like Veith, Gray pointed to the potential of the ENROUTE system, tested in the ROADSTER study of 141 patients, to prevent such damage. “Reverse flow only took place for about 10 minutes, high reverse flow for only 9 minutes. And the results were striking,” he commented. “There were no major strokes in this trial.” Two minor strokes occurred (1.4%), dropping to 1 minor stroke in the per protocol analysis (0.7% out of 136 patients). Among patients over age 75 and those who were symptomatic, there no major or minor strokes.

“This is the first carotid stent technology wholeheartedly embraced by the vascular surgical community. Period. That is unique,” Gray said.

Regarding mechanistic causes of stroke,” Gray agreed that “plaque protrusion does occur.” One-year follow-up on WL Gore’s scaffold stent will hopefully be available in 2018, he said, also referencing the CGuard and Roadster devices. He reported that the incidence and volume of new diffusion-weighted MRI lesions is lower with CGuard than with historical controls.

“Mesh-covered carotid stents, double filtration, direct carotid access with embolic protection are likely to add benefits in terms of reducing not only clinical events but also surrogate DWI lesions, which I believe are a marker for those small but increased minor stroke rates,” Gray concluded.