Endovascular Management of Intracranial and Extracranial

Atherosclerosis

Rishi Gupta, MDAssociate Professor of Neurology, Neurosurgery, and Radiology

Emory University School of MedicineDirector,Multi-Center Acute Stroke Network

Marcus Stroke and Neuroscience CenterGrady Memorial Hospital

Extracranial Carotid Artery Disease

700,000 Strokes annually in the US 1

Extracranial carotid artery disease accounts for 10-15 % of Ischemic Cerebral Infarctions 2

Causes cognitive impairment 3

11Ovbiagele et al. , Stroke 20032 2 Whisnant 19953 3 Rao et al., Stroke 1999Rao et al., Stroke 1999

Natural History of Carotid Disease

Strongest predictors of future events 1

Prior ipsilateral hemispheric symptoms Degree of stenosis

Other predictors of future events Unstable plaque 2 (ulceration, intraplaque

hemorrhage, intraluminal thrombus) Hemodynamic impairment 3,4,5

Coexistence of both 6

11 Rothwell, Stroke 2000,Rothwell, Stroke 2000, 2 2 Rothwell, Cerebrovasc. Dis. 2001, Rothwell, Cerebrovasc. Dis. 2001, 33 Silvestrini JAMA 2000, Silvestrini JAMA 2000,

44Markus, Brain 2001, Markus, Brain 2001, 55Yonas, J Neurosurg 1993 , Yonas, J Neurosurg 1993 , 66Caplan, Arch Neurol 1999Caplan, Arch Neurol 1999

Carotid Endarterectomy for Symptomatic High Grade Carotid Stenosis (NASCET)

659 patients with ischemic stroke or TIA

andCarotid stenosis 70%-99%

Carotid Endarterectomy

(n=328)

Medical management

(n=331)

9% 26%Ipsilateralstroke

2 years

P < 0.0001

NNT=8NASCET investigators, NEJM 1991

Complications: stroke/death 5.8%

Carotid Endarterectomy for Symptomatic Moderate Grade Carotid Stenosis (NASCET)

858 patients with ischemic stroke or TIA

AndCarotid stenosis 50%-69%

Carotid Endarterectomy

(n=428)

Medical management

(n=430)

15.7% 22.2%Ipsilateralstroke

5 years

P = 0.045

Barnett et al, NEJM 1998 NNT=20

Complications: stroke/death 6.7%

Carotid Endarterectomy for Asymptomatic Moderate-Severe Carotid Stenosis (ACAS)

1662 patients with asymptomatic

Carotid stenosis 60%-99%

Carotid Endarterectomy

(n=825)

Medical management

(n=834)

5.1% 11%IpsilateralStroke, Death

5 years

P = 0.004

ACAS investigators, JAMA 1995 NNT= 48

Complications: stroke/death 2.3%

Asymptomatic Carotid Surgery Trial (ACST)

3120 patients with asymptomatic

Carotid stenosis 60%-99%

Carotid Endarterectomy

Medical management

6.4% 11.8%Stroke, Death

5 years

P = 0.001

ACST Investigators, Lancet 2004

Asymptomatic Carotid Stenosis

Interestingly, with a decade between ACAS and ACST, natural history of asymptomatic carotid stenosis did not change

Rates of anti-platelet therapy use higher in ACAS and statin implementation higher compared to ACAS

High Surgical Risk for CEA

Risk factors– Age > 75– Ipsilateral carotid occlusion– Carotid siphon stenosis– Intraluminal thrombus

Not considered– MI within 6 months– Severe hypertension– CHF– COPD– Severity of stenosis– Contralateral carotid stenosis– Ulceration

Goldstein et al. Stroke 25;1116, 1994

High Surgical Risk for CEA

Risk Factors # Pts MI, Str, Dth

0 482 6.4%

1 197 12.2%

2 16 18.8%

3 2 50.0%

1-3 215 13.0%

• 1160 CEAs at 12 hospitals - Retrospective review

Goldstein et al. Stroke 25;1116, 1994

Carotid Artery Stenting/Angioplasty (CAS)

First performed in the 1980’s Early clinical trials for high risk

CEA patients - Clinical registries, SAPPHIRE More recently, RCT comparing to

CEA in low risk patients

SAPPHIRE: Study Design

Randomized, multi-center trial comparing carotid stenting with protection vs. endarterectomy in high surgical risk patients

Prove Non-Inferiority of Stenting with EDP vs. CEA

80% Asymptomatic carotid stenosis or 50% symptomatic carotid stenosis

Non-randomized patients entered in stent registry or surgical registry

Stroke, MI and Death (Composite outcome)– 30-day post- procedure

Key Inclusion Criteria: > 1 Comorbidity (Systemic)

Congestive heart failure (class III/IV) and/or

known severe LV dysfunction (LVEF <30%)

Open heart surgery needed within six weeks

Recent MI (>24 hrs. and <4 weeks)

Unstable angina (CCS class III/IV)

Severe pulmonary disease

Age greater than 80 years

Randomized Study-All Patients 30 Days Events (N= 156 vs 151)

3.8%

5.3%

2.6%

7.3%

0.6%

2.0%

5.8%

12.6%

0%

2%

4%

6%

8%

10%

12%

14%

Stroke MI Death Stroke/MI/D

StentingCEA

P=0.047

Randomized trial Randomized trial 1:1 CEA vs CAS1:1 CEA vs CAS Designed to prove non-inferiorityDesigned to prove non-inferiority Symptomatic patients with Symptomatic patients with 60% 60% 524 patients enrolled524 patients enrolled Stopped prematurely due to safety and Stopped prematurely due to safety and

futilityfutility

EVA 3S

EVA 3S - IssuesEVA 3S - Issues

Operator experienceOperator experience ::

– 12 carotid stents does not require 014 experience12 carotid stents does not require 014 experience– 35 supraaortic stents (of which 5 carotids) or35 supraaortic stents (of which 5 carotids) or– performance of stenting under supervision by proctor who performance of stenting under supervision by proctor who

fullfills above criteriafullfills above criteria

No requirement for :No requirement for : - dual antiplatelet therapy (15% without)- dual antiplatelet therapy (15% without) - uniform stent/protection device - uniform stent/protection device - use of protection device (10% without)- use of protection device (10% without)

SPACE

-Randomized trial Randomized trial

-1:1 CEA vs CAS-1:1 CEA vs CAS

- Designed to prove non-inferiority- Designed to prove non-inferiority

- Symptomatic patients with - Symptomatic patients with 50% (NASCET) 50% (NASCET)

- 1200 patients enrolled- 1200 patients enrolled

-Stopped prematurely due to lack of funding-Stopped prematurely due to lack of funding

SX ICA WITH LARGE ULCERATION SX ICA WITH LARGE ULCERATION TREATED WITH EMBOLI PREVENTION TREATED WITH EMBOLI PREVENTION FILTERFILTER

Filter

PRE FILTER POST

EMBOLIZEDPLAQUE

EMBOLIZEDPLAQUE

CREST

Randomized controlled study of 2502 patients with conventional risk

1:1 randomization to CAS vs. CEA Included symptomatic and

Asymptomatic patients Primary endpoint of any stroke, death

or MI Rigorous vetting process with a lead in

phase for investigators and prior experience with a pre-defined 6% complication rate in the past

Peri-procedural Stroke and MI

 CAS vs. CEA

Hazard Ratio 95% CIP-Value

Stroke

4.14.1 vs.

2.32.3%

HR = 1.79; 95% CI: 1.14-2.82

0.01

MI1.11.1 vs.

2.32.3%

HR = 0.50; 95% CI: 0.26-0.94

0.03

Primary Endpoint ≤ 4 years(any stroke, MI, or death within peri-procedural period

plus ipsilateral stroke thereafter)

CAS vs. CEA

Hazard Ratio, 95% CIP-

Value

7.27.2 vs.

6.86.8%%HR = 1.11; 95% CI:

0.81-1.510.51

0

1

2

3

4

40 50 60 70 80 90

Haz

ard

Ratio

Age (Years)

Pinteraction = 0.020

CEA Superior

CAS Superior

Primary outcome – 4 year

Study # Patients

Tutor Allowed

Stent Type Dual Anti-platelet

EPD Use 30 day stroke

CAVATAS 504 No Angioplasty Aspirin 0% 8%

EVA 3S 527 Yes Multiple 15% not on dual anti-platelets

91% 8.8%

SPACE 1200 Yes Multiple Mandated 27% 6.5%

ICSS 1710 Yes Multiple Recommended 72% 6.3%

CREST 2502 No Acculink Mandated Mandated 4.1%

SAPPHIRE 334 No Precise Mandated Mandated 3.6%

Summary of Randomized CAS Studies

Summary of Carotid Treatment

Carotid revascularization recommended for patients with moderate to severe stenosis:

- If Sx and survival > 2 years - If ASx and survival > 5 years

CEA and CAS are both options available for revascularization Multidisciplinary approach with surgery, endovascular specialist

and neurologist will likely yield best clinical outcome

As with ICAD, maximal medical therapy important towards reducing risk of stroke, MI long term

Conclusions

Medical management pre and post carotid revascularization may impact safety, durability of treatment

CAS will likely have a larger role in carotid revascularization after CREST.

Interest in cognitive differences between CAS and CEA, also ? if distal vs. proximal protection leads to reduced downstream emboli