Endovascular Management of
Intracranial and Extracranial
Atherosclerosis
Rishi Gupta, MD
Associate Professor of Neurology, Neurosurgery, and Radiology
Emory University School of Medicine
Director,Multi-Center Acute Stroke Network
Marcus Stroke and Neuroscience Center
Grady Memorial Hospital
Extracranial Carotid Artery
Disease



700,000 Strokes annually in the US 1
Extracranial carotid artery disease accounts for 1015 % of Ischemic Cerebral Infarctions 2
Causes cognitive impairment 3
1Ovbiagele
et al. , Stroke 2003
2 Whisnant 1995
3 Rao 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

1
2
3
Rothwell, Stroke 2000,
Rothwell, Cerebrovasc.6 Dis. 2001, Silvestrini JAMA 2000,
4
5
Markus, Brain 2001, Yonas, J Neurosurg 1993 , Caplan, Arch Neurol 1999
Carotid Endarterectomy for Symptomatic High
Grade Carotid Stenosis (NASCET)
Complications:
stroke/death
5.8%
659 patients with
ischemic stroke or TIA
and
Carotid stenosis 70%-99%
Carotid
Endarterectomy
(n=328)
Medical
management
(n=331)
2 years
Ipsilateral
stroke
9%
NASCET investigators, NEJM 1991
26%
P < 0.0001
NNT=8
Carotid Endarterectomy for Symptomatic
Moderate Grade Carotid Stenosis (NASCET)
Complications:
stroke/death
6.7%
858 patients with
ischemic stroke or TIA
And
Carotid stenosis 50%-69%
Carotid
Endarterectomy
(n=428)
Medical
management
(n=430)
5 years
Ipsilateral
stroke
15.7%
Barnett et al, NEJM 1998
22.2%
P = 0.045
NNT=20
Carotid Endarterectomy for Asymptomatic
Moderate-Severe Carotid Stenosis (ACAS)
1662 patients with
asymptomatic
Carotid stenosis 60%-99%
Complications:
stroke/death
2.3%
Carotid
Endarterectomy
(n=825)
Medical
management
(n=834)
5 years
Ipsilateral
Stroke, Death
5.1%
ACAS investigators, JAMA 1995
11%
P = 0.004
NNT= 48
Asymptomatic Carotid Surgery Trial
(ACST)
3120 patients with
asymptomatic
Carotid stenosis 60%-99%
Carotid
Endarterectomy
Medical
management
5 years
Stroke, Death
6.4%
ACST Investigators, Lancet 2004
11.8%
P = 0.001
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
• 1160 CEAs at 12 hospitals - Retrospective review
Risk Factors
0
# Pts
482
MI, Str, Dth
6.4%
1
197
12.2%
2
16
18.8%
3
2
50.0%
1-3
215
13.0%
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)
14%
12%
10%
12.6%
Stenting
CEA
P=0.047
7.3%
8%
5.8%
5.3%
6%
3.8%
4%
2.6%
2.0%
2%
0.6%
0%
Stroke
MI
Death
Stroke/MI/D
EVA 3S






Randomized trial
1:1 CEA vs CAS
Designed to prove non-inferiority
Symptomatic patients with  60%
524 patients enrolled
Stopped prematurely due to safety and futility
EVA 3S - Issues

Operator experience :
–
–
–

12 carotid stents does not require 014 experience
35 supraaortic stents (of which 5 carotids) or
performance of stenting under supervision by proctor
who fullfills above criteria
No requirement for :
- dual antiplatelet therapy (15% without)
- uniform stent/protection device
- use of protection device (10% without)
SPACE
-Randomized trial
-1:1 CEA vs CAS
- Designed to prove non-inferiority
- Symptomatic patients with  50% (NASCET)
- 1200 patients enrolled
-Stopped prematurely due to lack of funding
SX ICA WITH LARGE ULCERATION
TREATED WITH EMBOLI PREVENTION
FILTER
EMBOLIZED
PLAQUE
Filter
EMBOLIZED
PLAQUE
PRE
FILTER
POST
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% CI
Stroke
MI
4.1 vs.
2.3%
1.1 vs.
2.3%
PValue
HR = 1.79; 95% CI: 1.142.82
0.01
HR = 0.50; 95% CI: 0.260.94
0.03
Primary Endpoint ≤ 4 years
(any stroke, MI, or death within peri-procedural period
plus ipsilateral stroke thereafter)
CAS vs. CEA
7.2 vs.
6.8%
Hazard Ratio, 95% CI
HR = 1.11; 95% CI: 0.811.51
P-Value
0.51
Primary outcome – 4 year
4
Pinteraction = 0.020
Hazard Ratio
3
CEA Superior
2
1
CAS Superior
0
40
50
60
70
Age (Years)
80
90
Summary of Randomized CAS Studies
#
Patients
Tutor
Allowed
Stent Type
Dual Antiplatelet
EPD Use
30 day
stroke
CAVATAS
504
No
Angioplasty
Aspirin
0%
8%
EVA 3S
527
Yes
Multiple
15% not on
dual antiplatelets
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%
Study
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