Is there any future for carotid stenting?Proximal protection and

mesh-covered stents are the answer

Peter A. Schneider, MD

Kaiser Foundation Hospital

Honolulu, Hawaii

Disclosure

Peter A. Schneider

.................................................................................

I have the following potential conflicts of interest to report:

Scientific Advisory Board (non-paid): Cardinal, Abbott, Medtronic

Royalty (modest): Cook

Co-founder and Chief Medical Officer: Intact, Cagent

Enter patients into studies: NIH, Bard, Gore, Medtronic, BSI,

Silk Road (no financial relationship).

VIVA Board member (nonprofit)

Periprocedural Endpoints in CREST

Too Many Minor Strokes

1,081 Asymptomatic patients CASEvents (%)

CEAEvents (%)

P value

Major Stroke 3 (0.5) 2 (0.3) 0.66

Minor Stroke 12 (2.0) 6 (1.0) 0.15

Stroke and death 15 (2.5) 8 (1.4) 0.15

MI 7 (1.2) 13 (2.2) 0.76

Silver et al. Stroke 2011;42:675

1,321 Symptomatic patients CASEvents (%)

CEAEvents (%)

P value

Major Stroke 8 (1.2) 6 (0.9) 0.61

Minor Stroke 29 (4.3) 15 (2.3) 0.042

Stroke and death 40 (6.0) 21 (3.2) 0.019

MI 7 (1.0) 15 (2.3) 0.083

Too Many

DW-MRI HitsCAS: up to 70%

CEA: up to 27%

Leal et al. Eur J Vasc Endovasc Surg 2010;39:661

Most are temporary, not associated with neurologic deficits.

Not clear if there is associated long-term cognitive deficit.

Use as a surrogate end point for neurological risk.

Recent meta-analysis

CAS 40.3%

CEA 12.2%Garguilo et al. Plos 2015;10:137

How to get better results?

Prior to CAS During CAS After CAS

1h to 30d

CREST Randomization

High Risk for CAS?

• Tortuous arch

• Calcified arch

• Diseased great vessels

• Tortuous carotid artery

• Pre-occlusive lesion

• Heavy plaque burden

• Circumferential calcification

• Echolucent plaque

Future of Carotid Revascularization

Protection Devices

Method of Protection

Approach Advantages Disadvantages

Distal Filter Fixed or free-wire filter system

Most experience, most patients can be treated(Several approved)

Incomplete filtration, less versatile for crossing lesion

Cessation offlow

Distal occlusion Lowest profile for crossing lesion (Percu-surge)

Intolerance, vessel damage at balloon site

Cessation of flow

Proximal balloon occlusion

No need to cross lesion, can treat bad ICA lesion (Mo-Ma)

Adds risk in a bad arch, intolerance

Reversal of flow

Direct cervical-proximal clamp

Better removal of emboli, simple, avoid arch (T-CAR)

Neck incision, no good inhostile neck, intolerance

) .N<O/.,%P%32%+/E%B*373823>%+2%Q$Q%&' ((%

Z)[ )\L)

PROFI:

Prospective Randomized Trial of

Proximal Balloon Occlusion vs Filter

Bijuklic K et al. J Am Coll Cardiol 2012;59:1383

Fewer DW-MRI Hits

With Proximal Protection

Armour Trial(n=220)

MAE Total 2.7%

Major Stroke 0.9%

Minor Stroke 1.4%

Death 0.9%

MI 0

TIA 0.9%

Ansel et al. Catheter Cardiovasc Interv 2010;76:1

Proximal Protection Better than Distal Filter

Incidence of new ischemic lesions by DW-MRI

Stabile et al. JACC Cardiovasc Interv 2014;7:1177

Fewer MRI Hits with Proximal Protection Using MoMa

Proximal Protection (MoMa) Better than Distal Filter

Giri et al. JACC Cardiovasc Interv 2015;8:609

Stroke Location

10,200 patients in the NCDR CARE Registry

Non-ipsilateral events

were responsible for

1/3 to 1/2 of the strokes.

Bonati et al. Lancet Neurology 2010;1016:1474

ICSS MRI Subset

45% of the new

cerebral lesions

after CAS were

non-ipsilateral

What about non-ipsilateral lesions?

Stroke Risk at 30 Days with Distal Filter Protection

CREST Results CAS CEA

All Stroke 4.1% 2.3%

Ipsilateral Stroke 2.0% 2.3%

Almost half of the strokes

were non-ipsilateral

Proximal Protection with Reversed Flow

TCAR-Transcervical Approach

First commercial case in US

Roadster IIPIs Vik Kashyap and Peter Schneider

Planning enrollment of >600 cases

Protection during all phases

More efficient particle capture

Avoid the arch

ROADSTER 2:Clinical Outcomes

ROADSTER 1 ROADSTER 2 ROADSTER 2n=203 n=227 n=252

Patients with 30-day F/U

Patients with 30-day F/U

All Patients

Stroke/Death/MI 6 3.0% 2 0.9% 2 0.8%Stroke 1 0.5% 2 0.9% 2 0.8%Death 2 1.0% 0 0.0% 0 0.0%MI 3 1.5% 0 0.0% 0 0.0%

Stroke/Death 3 1.5% 2 0.9% 2 0.8%CNI (permanent) 0 0.0% 0 0.0% 0 0.0%

Patients Treated Per Protocol

ROADSTER 2 Stroke in Asymptomatic Patients = 0.5%

ROADSTER 2 Stroke in Symptomatic Patients = 1.3%

Amazing array of configurations and morphologies

What About the Stent?

ScaffoldingLesion containmentConformabilityFatigue resistanceEase of re-crossingVisibilityLow profile

Schnaudigel et al. Stroke 2008;39:911

Closed Open

Closed cell (n=48)

Open cell(n=48)

P value

27.3% 51.1% 0.020

Park et al. J Neurosurg 2013;119:

More DW-MRI Lesions

with Open Cell Stents

Prospective RCT: MRI Hits

Closed versus Open Cell Stents

More Plaque Prolapse with Open Cell Stents

Plaque prolapse between stent struts

deDonato et al. Eur J Vasc Endovasc Surg 2013;45:479

Plaque Prolapse

Open Cell Closed Cell

61.5% 17.6%

Wholey J Endovasc Ther 2009;16:178

More Neurologic Events with Open Cell Stents

Belgian-Italian RegistryBosiers et al. Eur J Vasc Endovasc Surg 2007;33:135

SPACE Trial Olav J et al. Stroke 2009;40:841

Closed Open

Neurologic Events After 24 Hours

Bosiers et al. Eur J Vasc Endovasc Surg 2007;33:135

2/3 of neuro

events were

delayed (1-30d)

0-24 hours 1-30d % of strokes that occurred after 24 hours

29 events 19 events 40%

Hill et al. Circulation 2012;126:3054

CREST-Timing of Stroke After Carotid Stenting

Mesh-Covered Stents

Roadsaver

Mesh coverage for sustained embolic prevention

Retrievable and repositionable

5Fr delivery

Closed cell, woven structure

Microvention/Terumo

– Confidence Trial-for US approval

– MRI Study• 30% had new MRI lesions, all resolved at 30dRuffino et al. Cardiovasc Intervent Radiol 2016;39:1541

– Roadsaver Italian Registry• 150 patients enrolled, MRI subset

• 30 days: No stroke, death or TIA

• 3 Italian centersNerla et al. Eurointervent 2016;12(5) Aug 5

– Clear Road Trial• Enrolling 100 patients

– Update by K Deloose

• 12 European centers

Mesh-Covered StentsGORE Carotid Stent

– Open Cell Nitinol

Frame

– Closed Cell 500 µ

lattice on outside of

Frame

– Permanently Bound

CBAS Heparin on all

device surfaces

Trial enrolled

Expect results at CX

Mesh-Covered Stents

SCAFFOLD Trial

Design-Prospective study comparing GORE® Carotid Stent to a performance goal developed from CEA outcomes

50 sites, 312 subjects.

Co-Pis: Bill Gray and Peter Schneider

Objective-Evaluate safety and efficacy of GORE® Carotid Stent in patients at increased risk for adverse events from carotid endarterectomy.

Primary endpoint-Death, stroke, or myocardial infarction through 30 days plus ipsilateral stroke between 31 days and 1 year.

Mesh-Covered Stents

CGuard Prime EPS

Polyethylene Terephthalate (PET)

20µ wide fiber micronet on a nitinol

stent

Attached to proximal and distal

crowns of the stent

InspireMD

CARANET Study-30 patient trial

No stroke or death at 30 days

New DW-MRI lesions at 48h: 37%J Schoefer et al. JACC: Cardiovasc Interv

2015;8: 1229.

IRON-Guard Multicenter Italian

Registry: 200 patients, 30 d

manuscript in publication. 2.5%

stroke, 20% new DW-MRI lesions Setacci et al. J Cardiovasc Surg

2015;56:787

Mesh Covered Stent Designs

Gore Terumo Roadsaver InspireMDCGuardTM

Design

Aperture Size 500µ 300µ 180µ

Materials PTFE mesh (Heparin coated)on nitinol stent

nitinol on nitinol PET MicroNetTM

on nitinol stent

CE Mark No Yes Yes

Future of Carotid Stenting

ConclusionHigher risk of minor stroke in perioperative period

with CAS. Must be improved to make CAS a

viable therapy.

Proximal protection appears to be more complete

than filters and similar to endarterectomy.

Mesh covered stents may provide better lesion

containment with less potential for embolization

through the stent.

Is there any future for carotid stenting?Proximal protection and

mesh-covered stents are the answer

Peter A. Schneider, MD

Kaiser Foundation Hospital

Honolulu, Hawaii