SEMINAR

ATHEROSCLEROTIC
CAROTID ARTERY
DISEASE
DR. BARUN KUMAR
17.08.2011
ATHEROSCLEROTIC CAROTID ARTERY
DISEASE
CAROTID ARTERY is affected by many disorders.

The most frequent cause is atherosclerosis, but
other causes include fibromuscular dysplasia
(FMD), cystic medial necrosis, arteritis, and
dissection.

Atherosclerosis is a systemic disease, and
patients with this typically face an escalated risk of
other adverse cardiovascular events, including
myocardial infarction (MI), peripheral arterial
disease (PAD), and death.
CAROTID ATHEROSCLEROSIS
The proximal internal carotid artery and the
carotid bifurcation are most frequently involved.

However, the origin of the middle cerebral
artery, the distal carotid artery, and the carotid
siphon may also be affected.

Ulceration frequently occurs, placing the patient
at higher risk for embolization or thrombosis

Risk factors for carotid artery
atherosclerosis
Hypertension
Hypercholesterolemi
a
Smoking


Diabetes mellitus
Obesity
Family history
The risk of stroke from carotid disease is
highest in patients who have recently
sustained a reversible neurologic event, such
as a transient ischemic attack

Signs/symptoms of carotid
vascular disease
TIA (Transient Ischemic Attacks): focal neurologic
defects with resolution of symptoms within 24 hours

RIND (Reversible Ischemic Neurologic Deficit):
transient neurologic defects lasting 24-72 hrs.

Amaurosis fugax: temporary blindness in one eye,
frequently described as curtain coming down due to
microemboli in retina.

CVA (Cerebrovascular accident): neurologic deficit
with permanent brain damage
Carotid bruits
An asymptomatic bruit may prompt the physician
to obtain evaluation of carotid artery
However, the annual incidence of stroke
ipsilateral to a bruit that is not preceded by a TIA
is 1 to 3%
Among patients with a carotid bruit, only 35%
have a hemodynamically significant lesion (70 to
90% stenosis)
Conversely, among patients with
hemodynamically significant stenosis, only about
one-half have a bruit detectable on physical
examination

Outcome in patients with
asymptomatic neck bruits
prospectively followed 113 asymptomatic

patients
with carotid stenosis 75% (Doppler)
1 year 18% had ischemic cerebrovascular events
over of these events strokes (5.5%)
At 2 years 22% had ischemic cerebrovascular
events
In patients with less than 75% stenosis
1 year 3%
2 years 6%
Chambers BR, Norris JW. Outcome in patients with asymptomatic neck bruits. N Engl J Med 1986;315:860-865
Outcome in patients with
asymptomatic neck bruits 1986
Evaluating carotid disease
Duplex Doppler ultrasonography
Carotid Doppler ultrasonography
Transcranial Doppler
Magnetic resonance angiography (MRA)
Carotid angiography (gold standard)

Sensitivity/specificity of noninvasive tests to
predict stenoses >70% is 83-86%/89-94%
STROKEEpidemiology
>50% of the 731,000 strokes/yr in US results from extracranial
atherosclerotic carotid artery disease.
Account for 160,000 deaths per year in the United States.
Leading cause of disability.
Half of the patients that survive a stroke are permanently
disabled.
3
rd
. Leading cause of death after CAD & cancer in US.
Ischemic events are four times more frequent than hemorrhagic
events.
Atherosclerotic extracranial carotid artery disease usually cause
symptoms as a result of embolic events.
Carotid occlusive disease accounts for nearly one third of all
ischemic stroke cases.
The incidence of ischemic strokes increases with age (33% if
age 45 years and 80% if age 50 years).


How are TIA and stroke
related?
Pt. with TIA:
1 in 20 ( 5% ) chance of stroke within 30
days
25% will have recurrent CVA within 1 yr
35% of patients with a TIA will have a stroke in
their lifetime
50% of these will occur in the year following first
TIA
After first year stroke risk is 5% per year

Stroke
Prognosis
80% survive initial event
29% regain normal function
36% return to work
18% unable to work, but can take care of themselves
4% require custodial care
Natural history
only 50% of stroke victims will be alive at five
years.

What is the risk of stroke with asymptomatic
carotid stenosis?

Rates of stroke among asymptomatic
patients with carotid stenosis of at
least 80% of the luminal diameter are
approximately 3.5 to 5.0% per year.
Medical Treatment
Both systolic and diastolic blood pressure
independently related to stroke incidence
6mm reduction in DBP produces 42% reduction in
stroke rate
Tx of isolated systolic hypertension in patients over 60
reduces stroke incidence by 32%
Smoking cessation
Relative risk 1.5-2.2
Serum lipid levels
have not been shown to affect stroke rate but low
levels slow progression of atherosclerosis

Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing
group of the stroke council, american heart association. Circulation 1998;97:501-509
Medical Treatment
Alcohol consumption
Heavy alcohol use associated with excessive
stroke risk
Moderate consumption may have no or a slightly
protective effect
Antiplatelet therapy
23% reduction in stroke with aspirin compared to
placebo in patients with history of TIA/stroke
Also 22% reduction in MI/death

Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing
group of the stroke council, american heart association. Circulation 1998;97:501-509


Comparison of measurement of ICA stenosis using NASCET
(angiographic) criteria or ECST (Duplex ultrasound) criteria.

Carotid Endarterectomy
(CEA)
Surgical removal of the inner layer of the carotid
artery when narrowed by atheromatous intimal
plaques
Carotid endarterectomy
Performed through neck incision, usually along
sternocleidomastoid muscle
Proximal and distal control of artery is obtained
While patient is heparinized, internal and
external carotid arteries are clamped
Longitudinal arteriotomy is performed, carotid
plaque is removed, and vessel is closed over a
patch
North American Symptomatic Carotid Endarterectomy
Trial (NASCET)
Randomized trial of CEA vs anti-
platelet therapy
50 centers in US and Canada
1987-1996
659 patients with stenosis >70%
2226 patients with stenosis < 70%
Patients:
<80 years old
Non-disabling stroke or retinal or
hemispheric TIA within 120 days
Exclusion:
Disease limiting life expectancy to <5
years
Carotid artery stenosis:
30-69% or 70-99%
Defined by angiography
Medical treatment:
Anti-thrombotic medication
Mostly aspirin (dose not specified)
Anti-hypertensive and lipid lowering
agents at the discretion of the treating
physician
Surgical treatment:
Medical treatment as above
CEA

Peri-operative stroke or death:
Net increase in surgical risk of any
stroke or death of 4.3%
1.4% net increase in disabling
stroke or death
Long-term Result:
70-99% group:
CEA had 17% absolute risk reduction
for stroke at 2 years
50-69% group:
CEA had a 7% absolute risk
reduction at 5 years
30-49% group:
No difference
Conclusions:
CEA recommended for
symptomatic carotid artery
stenosis of 70-99%
In centers with low peri-operative
stroke rate and in select patients,
CEA can be utilized for
symptomatic stenosis of 50-69%
NEJM 1991 & 1998
NASCET.NEJM.19
91
NASCET 1998
Does CEA benefit symptomatic pts with
stenosis <70%
Any ipsilateral stroke at 5 years
50-69% stenosis
15.7% CEA
22.2% medical
<50% stenosis
14.9% CEA
18.7% medical (not statistically significant)

NASCET 1998
CEA in symptomatic patients with 50-69%
yields only moderate reduction in risk of stroke
and provided no benefit to patients with <50%
stenosis.
Patients with 70% stenosis had durable
benefit at eight years.
778 symptomatic patients / 3 yrs
Stenoses > 70%
Risk of CVA
Clinical treatment = 16,8%
Surgical treatment = 2,8%
p < 0,001
Risk CVA/peri-operatory deaths =7,5%
ECST (European Carotid Surgery Trials)
Lancet 1991;337:1235
Can CEA reduce the stroke risk in
symptomatic patients?
CEA reduces the risk of any stroke from 25% to
10% at two years in patients with symptomatic
stenosis of 70% (NASCET)
Can CEA reduce the stroke risk in
asymptomatic patients?

Veterans Affairs Trial, 1993
Asymptomatic Carotid Stenosis Veterans
Administration Study
11 centers, 1983-1991
444 men with asymptomatic carotid stenosis
50% stenosis or more (angiogram)
Evaluated combined incidence of TIA, Amaurosis
Fugax, and stroke
Randomized to optimal medical treatment alone
vs. optimal medical treatment plus carotid
endarterectomy

Hobson RW 2
nd
, Weiss DG, Fields WS, Goldstone J, Moore WS, Towne JB, Wright CB. Efficacy of carotid endarterectomy for asymptomatic carotid
stenosis. The Veterans Affairs Cooperative Study Group. N Engl J Med. 1993 Jan 28;328(4):221-7.
Veterans Affairs Trial, 1993
All patients followed for an average of 48
months
Incidence of ipsilateral neurologic events
8% CEA
20.6% medical group
Stroke/death rate within 30 days not different
between groups
Veterans Affairs Trial, 1993
Incidence of Neurologic End Points for Ipsilateral Events.
Veterans Affairs Trial, 1993
Asymptomatic Carotid Atherosclerosis Study
(ACAS)
Randomized trial of CEA vs anti-
platelet therapy
39 centers in US and Canada
1988-1993
1662 patients
Patients
Age 40-79
Exclusion criteria:
Severe comorbidities
disease likely to cause death
w/in 5 yrs
Any cerebrovascular event
Contra-indication to aspirin
Carotid artery stenosis
>60% stenosis
Defined by angiography or
doppler US
Same angiographic definition
as NASCET
Medical treatment:
325mg aspirin daily
Recommendations on risk factor
reduction
No angiography required
Surgical treatment:
Aspirin & risk reduction
Angiography required
CEA
Peri-operative risk of stroke or death:
Surgery: 2.3%
5 strokes secondary to
angiography
Medical: 0.4%
5-year results:
6% absolute risk reduction for stroke
Conclusions:
CEA recommended for patients
with > 60% stenosis
In centers with low peri-operative
mortality and stroke rates (<3%)
In patients with good overall health
JAMA 1995
Asymptomatic Carotid Surgery Trial
(ACST)


Randomized study of immediate vs. indefinite
deferral of CE

5 five year follow-up at 126 centers in 30 countries

% diameter reduction stenosis by carotid
ultrasound

Eligibility = carotid artery diameter reduction of at
least 60% on ultrasound and no symptoms within
the past six months

Enrollment 1993 2003 planned 10 year follow-up

3120 randomized patients - 2 groups of 1560 each
Perioperative events (stroke and death within 30
days) and the non-perioperative strokes combined
Net 5 year risks were 6.4% (immediate CE) versus
11.8% (deferred CE) for all strokes; 3.5% vs. 6.1% for
fatal or disabling strokes

Gain mostly in non-perioperative carotid territory
ischemic strokes

The benefit was seen in both contralateral and
ipsilateral carotid-territory strokes
Asymptomatic Carotid Surgery Trial
(ACST)

Subgroup analyses showed

benefits were significant for those < 65 years, those
between 65 and 74 years, but uncertain for those > 75
years
Men and women both benefited but there were only a
total of 40 non-perioperative strokes in women so the
results were not as definite (p=0.02)
5 year benefit of CE appeared to be as great for those
with <80% diameter reduction (mean 69% stenosis) as
for those with 80-99% (mean 87%) reduction
No significant difference in results in those patients who
were never symptomatic compared to those with
symptoms > six months previously (7.1% and 4.6%
absolute five year gain, respectively)
Asymptomatic Carotid Surgery Trial
(ACST)



Complications of carotid
endarterectomy



Cardiac events
Postoperative
stroke
Hyperperfusion
syndrome
Nerve injury

Bleeding
Infection
Parotitis
Re-stenosis

Hyperperfusion syndrome
Cerebral hyperperfusion is the leading cause of
intracerebral hemorrhage and seizures during the first
two weeks following CEA.

Causes changes in low-flow carotid vascular bed.

Small vessels compensate by dilating, then cannot re-
constrict properly and therefore cannot protect
vascular bed

Nerve injury
Nerves at risk for injury during CEA include:
Vagus nerve
Recurrent laryngeal nerve
Facial nerve
Glossopharyngeal nerve
Hypoglossal nerve
Branches of trigeminal nerve
Randomized controlled trials evaluating medical
management vs. carotid endarterectomy for
ipsilateral
stroke prevention in patients with carotid artery
stenosis
Conditions associated with an
increased operative risk for carotid
endarterectomy
Can CEA reduce the stroke risk in
asymptomatic patients?
CEA reduces the risk of any stroke or death from
11% to 5% at five years in patients with
asymptomatic stenosis of 60% (ACAS)
What about stenting?

Patients with high risk of stroke present
also with high risk for surgical treatment
Brown et al. J Vasc Surg, 2003; 37:32
Gasparis et al. J Vasc Surg 2003; 37:40
High risk
patients
Endovascular
Treatment
Carotid artery stenting procedure. Following engagement of the common
carotid artery (CCA) with a guiding catheter or long sheath, the lesion in the
internal carotid artery (ICA) is passed with a wire or with the filter emboli
protection device (A). Subsequently, a self-expanding stent is deployed, usually
covering the carotid bifurcation (B and C). Thereafter, a balloon post-dilatation
is performed to achieve good stent expansion (D). ECA, external carotid artery.
Advantages of the Percutaneous Approach in Carotid
Interventions
Conditions associated with increased procedural risk
and contraindications for carotid artery stenting
Carotid angioplasty and
stenting
The first case reports of carotid artery
angioplasty were reported in the early 1980s.

Carotid angioplasty and
stenting
Roubin GS, Yadav S, Lyer SS, et al. Carotid stent supported angioplasty: a neurovascular intervention to
prevent stroke. Am J Cardiol 1996;78:8-12.
The first large series of carotid angioplasty and
stenting was reported by Roubin et.al. in 1996
They preformed angioplasty in 107 patients
deemed too medically/anatomically unstable to
undergo endarterectomy.
10% combined stroke/death rate
Carotid angioplasty and
stenting
In 2000 a large multicenter report (14 groups)
in which 358 arteries in 338 patients with
restenosis after CEA was published.
5 year follow-up
Stroke rate 3.7%
Mortality 1.1%
Adverse events 4%

New G, Roubin GS, Iyer SS, et al. Safety, efficacy, and durability of carotid artery stenting for restenosis following carotid endarterectomy: a
multicenter study. J Endovascul Ther 2000;7:345-352.
Carotid angioplasty and
stenting
Mathias K, Jager H, Hennigs S, et al. Endoluminal treatment of internal carotid artery stenosis. World J
Surg 2001;25:328-334.
In 2001 Mathias et al. presented data on over
3,000 carotid artery stents (CAS).
Stroke rate 2%
Complication rate 3%

These and other series demonstrated that
stenting could be preformed with an
acceptable complication rate.
3 types of studies available to review efficacy
of stenting
Case series
Industry sponsored registries
Randomized trials

In
Case Series
51% patients symptomatic
>97% successfully stented
64% evaluated by neurologist
After 2002 embolic protection devices (EPDs)
widely utilized
Case Series
Stroke rate 1% - 8% (lower with experience
and EPD use)
Overall 30 day stroke rate 3%
Overall 30 day stroke/MI/death rate 4%
Early restenosis rates 1%-8% (reported in half
the series)

There is considerable evidence of
embolization during carotid angioplasty
DeMonte et al. J Neurosurg. 1989;70:138
Ohki, T et al. J Vasc Surg. 1998;27:463
Industry-sponsored registries of
CAS
Industry-sponsored registries of
CAS
Presented at national meetings but not
published in peer reviewed journals
30 day stroke rates 2%-7%
30 day stroke, MI, death rates 3%-8%
27% of patients symptomatic

CEA/CAS Randomized Controlled
Trials
ICSS
CREST
CEA/CAS BACKGROUND INFORMATION
CEA/CAS BACKGROUND INFORMATION
Randomized trials
All used independent neurologist examinations
After 2001, all used EPDs


WALLSTENT TRIAL


219 patients
No protection
No antiplatelet therapy
Surgical
4,5%
Endovascular
12,1%
Risk CVA/death
Trial was interrupted
Stroke 2001;32:325

The Carotid and Vertebral Artery
Transluminal Angioplasty Study
(CAVATAS)

First multicenter RCT comparing CEA and CAS.

Stenting was rolled late into the trial. 24 centers in Europe,
Australia, and Canada enrolled 504 pts.

High-risk surgical pts were excluded. Mixed symptomatic and
asymptomatic pts.

253/504 randomized to CEA and 251/504 to endovascular tx (65
received stents, 26%). No distal protection device.

Results: No statistically significant difference between both arms in
the rate of stroke, death or MI within 30 days and 1-year stroke or
death rates

Encouraging results generated interest in CAS, and inspired more
studies to be undertaken.

Lancet. 2001
CAVATAS: Endpoint events at 30 days
Carotid angioplasty
and stenting
Endpoint
CAVATAS investigators. Lancet 2001; 357: 1729-37.
CAVATAS


Disabling stroke
or death
Any stroke > 7
days, death
Carotid
endarterectomy
6.4%
p value
5.9% NS
10.0% 9.9% NS
CAVATAS: Complications
Carotid angioplasty
and stenting
Endpoint
CAVATAS investigators. Lancet 2001; 357: 1729-37.
CAVATAS


Cranial
neuropathy
Major groin or
neck hematoma
Carotid
endarterectomy
0 (0%)
<0.001
p value
22 (8.7%) <0.0001
3 (1.2%)
Severe ipsilateral
carotid stenosis
17 (6.7%) <0.0015
25 (14%) 7 (4%)
Carotid Revascularization Using Endarterectomy or
Stenting Systems (CaRESS)
Prospective non-randomized
cohort study
14 centers in US
397 patients
254 CEA, 143 CAS
Standard CEA versus CAS with
cerebral protection device
Patients:
Similar patient demographics
68% asymptomatic
>90% with >75% stenosis
Significantly more prior CEA or stent
in the CAS arm

Peri-operative stroke or death:
CEA: 2.4%
CAS: 2.1%
4 year follow up results:
Any stroke:
CEA 9.6%, CAS 8.6%
Death/ non-fatal stroke:
CEA 26.5%, CAS 21.8%
Restenosis:
Significantly higher in CAS arm
Conclusion:
Proof of principle that CAS with
distal protection should be
compared to CEA in a broad
patient sample in a randomized
trial
J Endovasc Ther 2003 & 2009
SAPPHIRE 2004
Stenting and Angioplasty with Protection for
Patients at HIgh Risk for Endarterectomy
(SAPPHIRE) trial
Data at 30 days and 1 year & 3 year
EPDs used on all patients
334 patients
50% symptomatic stenosis
80% asymptomatic stenosis

Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid artery stenting verses endarterectomy in high-risk patients. N Engl J Med 2004;
351:1493-1501.

SAPPHIRE 2004
SAPPHIRE
High risk for CEA
Clinically significant heart disease
Severe pulmonary disease
Contralateral carotid occlusion
Contralateral laryngeal nerve palsy
Previous radical neck surgery or radiation therapy
Recurrent stenosis after CEA
Age > 80 years


Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid artery stenting verses endarterectomy in high-risk patients. N Engl J Med 2004; 351:1493-1501.

SAPPHIRE 2004
Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid artery stenting verses endarterectomy in high-
risk patients. N Engl J Med 2004; 351:1493-1501.
SAPPHIRE
Randomized to CEA or CAS
30 day stroke/MI/death rate
4.4% CAS
9.8% CEA
1 year stroke/MI/death rate
12% CAS
20% CEA
High rates in CEA group secondary to high risk
patients
Conclusion CAS with EPD not inferior to CEA in high
risk patients




SAPPHIRE 2004
Flaws with SAPPHIRE
Supported by Cordis Corp. manufacturer of stent used in
study [use of a self-expanding,nitinol stent (Smart
or Precise, Cordis) and an emboli-protection
device (Angioguard or Angioguard XP Embolic
Capture Guidewire, Cordis)]
747 pts evaluated only 334 randomized (406 entered into
stent registries, 7 referred for CEA)
Stopped after 334 pts out of planned 2,900 pts enrolled
due to competing nonrandomized registries
Troponin based MI
non-Q-wave MI have 27 fold increased risk of MI in the next 6
months
This was not borne out in the long-term outcomes

Gurm, HS, Yadav JS, Fayad, P M.D.et.al.Long-Term Results of Carotid Stenting versus Endarterectomy in High-Risk
Patients. N. Engl. J. Med. 2008;358:1572-9
SAPPHIRE 2004
SAPPHIRE was used to gain FDA approval of
the Cordis stent
6 cardiologists, 2 interventional radiologists, 2
vascular surgeons, 1 neurologist on panel
Approved 6 to 5
SAPPHIRE 2008
3 year data, primary endoints plus death or
ipsilateral stroke at 3 years
24.6% CAS
26.9% CEA
15 strokes in each group
11 ipsilateral in the CAS group
9 ipsilateral in the CEA group
Conclusion no difference in longterm
outcome
SPACE Lancet 2006
To establish noninferiority for CAS in symptomatic pts with CS
50% and with low surgical risk.

Multicenter randomized trial throughout Germany, Austria, and
Switzerland.

Primary endpoints were ipsilateral ischemic stroke or death
from randomization to 30 days post procedure.

All patients received aspirin preprocedure.

1200 pts randomized, 595 to CEA and 605 to CAS.

SPACE Lancet 2006

At 30 days, ipsilateral stroke or death was not different,
6.35% for CEA and 6.8% for CAS (P = .09).
Distal protection used only in 27%; subgroup analysis
showed no difference between pts with cerebral protection
and those without. Stroke 2009
The trial was stopped as result of interim analysis
demonstrated that 2500 patients would be needed to reach
significance and determine noninferiority of CAS given the
results up to that point.
The SPACE steering committee acknowledged a lack of
funds to expand enrollment to 2500 and therefore
suspended the trial.
In the final analysis, the SPACE trial failed to prove
noninferiority of stenting versus endarterectomy as
measured by stroke/death rates at 30 days post procedure
in symptomatic patients with CS.
SPACE Lancet Neurol 2008
1214 patients were randomly assigned (613
CAS and 601 CEA).
At 2 years follow-up:
Primary and secondary endpoints were similar.
Recurrent stenosis (70% ECST) defined by
ultrasound was more frequent in CAS group. Only two
incidences of recurrent stenosis after carotid artery
stenting led to neurological symptoms.
SPACE 2006,2008
Interpretation:
Symptomatic pts with CS and low surgical risk, SPACE
failed to prove noninferiority of CAS for lack of power
from 1214 patients recruited. However, there was no
statistical difference in the rate of outcome events

These results can be interpreted differently:
A vascular surgeon may point out that an equal effect between
CEA and CAS was not shown with SPACE because equivalence
was missed (P0.09, one-sided value for noninferiority).
Interventionalists have focused on the fact that there was no
statistical difference in the outcome event rates between CEA and
CAS (P0.81, ChiSquare test)
EVA-3S N Engl J Med 2006

Similar to the SPACE trial, RCT designed to assess noninferiority of CAS
versus CEA in low-risk, symptomatic patients with CS 60%.
Multicenter study conducted in France. Primary endpoint was 30-day
stroke or death.
The study was stopped after enrollment of 527 pts for reasons of safety
and futility.
Primary endpoint was 3.9% CEA vs. 9.6% CAS (P = .01).
Protection devices was not required initially. Pts treated without protection
had 25% rate of stroke or death at 30 days (5/20), prompting protocol
changes.
CAS operators had unequal experience compared to surgeons performing
CEA.
EVA-3S N Engl J Med 2006
Risk was 9.6% higher than other RCTs. The absolute risk increase of
stenting was 5.7%, and for every 17 cases treated with CAS rather
than CEA, 1 additional stroke or death occurred at 30 days post
procedure.

The overall incidence of disabling stroke within 30 days was 3.4%
for CAS, 1.5% for CEA.

A significantly greater proportion of strokes occurred on the same
day of the procedure in the stenting group than in the surgical group
(P = .05).

Conclusion: Patients with symptomatic CS of 60%, CAS was
inferior to CEA with respect to the incidence of stroke and death at
30 days post procedure??

ICSS/CAVATAS-2 Lancet. 2010 Feb 25.

International Carotid Stenting Study: An interim analysis.

CAS vs. CEA in patients with symptomatic carotid stenosis.
Patients are low-risk equally suited for CAS or CEA

Multicentre, international, randomized controlled trial

The primary outcome: 3-year rate of fatal or disabling stroke in
any territory, which has not been analyzed yet.

The main outcome measure for the interim safety
analysis:120-day rate of stroke, death, or procedural MI.
Analysis was by intention to treat (ITT).

1713 patients (CAS 855; CEA 858).

Disabling stroke or death: CAS 4.0% vs. CEA
3.2% (hazard ratio [HR] 1.28, 95% CI 0.77-2.11).

Stroke, death, or procedural MI: CAS 8.5% vs.
CEA 5.2% (HR 1.69, 1.16-2.45, p=0.006).

Risks of any stroke (CAS 65 vs CEA 35 events;
HR 1.92, 1.27-2.89) and all-cause death (CAS 19
vs CEA 7 events; HR 2.76, 1.16-6.56)
ICSS/CAVATAS-2
ICSS/CAVATAS-2

Procedural MI: CAS 3 all fatal; CEA 4 all non-fatal.

Cranial nerve palsy CAS 1; CEA 45.

There were fewer hematomas of any severity in the
stenting group than in the endarterectomy group
(31 vs. 50 events; p=0.0197).

Conclusion: Completion of long-term follow-up is
needed to establish the efficacy of CEA vs. CAS.

Meanwhile, CEA should remain the treatment of
choice for patients suitable for surgery.

CREST
Carotid Revascularization Endarterectomy versus
Stenting Trial
Prospective randomized CEA vs. CS as prevention
of stroke in sxs & asxs patients
Composite primary endpoint of any periprocedural
stroke/MI/death OR ipsilateral stroke on f/u
n = 2502 17 centers North America (CEA 1240, CS
1262)
CREST
Primary and Secondary Endpoints
Primary endpoint
Peri-procedural a composite of:
Any clinical stroke
Myocardial infarction
Death
Post-procedural
Ipsilateral stroke up to 4 years

Secondary endpoint
Differential efficacy based on symptomatic status,
gender and age

CREST: Results
Primary endpoint
Carotid angioplasty/stenting: 7.2% / 4 years
Carotid Endarterectomy: 6.8% / 4 years
P value 0.51

Peri-procedural stroke
CAS 4.1 % CEA 2.3% HR 1.79, p=0.01

Peri-procedural MI
CAS 1.1% CEA 2.3% HR 0.50, p=0.03


CREST: Conclusions
Similar Primary Endpoint driven by differences in peri-
operative stroke and MI
More MIs after CEA
More strokes after CAS

CEA and CAS have similar net outcomes though the
individual risks vary, lower stroke with CEA and lower MI
with CAS

Younger patients may have improved efficacy with CAS
and older patients have improved efficacy with CEA

CAS/CEA - WHERE DE WE
STAND?
EVA 3S Conclusion: Patients with symptomatic CS
of 60%, CAS was inferior to CEA with respect to
the incidence of stroke and death at 30 days post
procedure??

ICSS Conclusion: CEA should remain the
treatment of choice for patients suitable for surgery.

CREST Conclusion:
30 d. any stroke rate (CAS 4.1% vs. CEA
2.3%) ss Major strokes < 1% both groups
nss
Periprocedural MI (CAS 1.1% VS. CEA
2.3%) ss



FDA Approved Devices
SAPPHIRE trial by Cordis
FDA approval of angioguard system in April 2004
ARCHeR registry by Guidant
FDA approval for Accunet/Acculink system in
August 2004
SECURITY registry by Abbott
FDA approval for Xact/Emboshield system in
September 2005

Pre- and Postprocedural Checklist for Carotid
Procedures
The Type I aortic arch is characterized by the origin of all 3 major vessels in the horizontal plane defined by
the outer curvature of the arch. Type I arch has the origin of all the great vessel within one diameter of the
ICA away from each other.

In Type II, the brachiocephalic artery originates between the horizontal planes of the outer and inner
curvatures of the arch. It has the take-off of the brachiocephalic artery >1 ICA diameter away from the other
great vessels

In Type III, the brachiocephalic artery originates below the horizontal plane of the inner curvature of the
arch.
Types of Aortic
Arch
Bovine Aortic Arch
A frequent variant of
human aortic arch
branching in which the
brachiocephalic and
left common carotid
arteries share a
common origin.

Occurs in about 27%
of people

This anatomy is not
generally found in
cattle, so the term
bovine arch is a
misnomer
The common carotid artery most commonly (in about 50% of
individuals) bifurcates at the level of the C4C5 intervertebral space (at
the level of the thyroid cartilage), giving rise to the ICA and external
carotid artery (ECA).

In about 38% of individuals, the carotid bifurcation will arise higher, at
about C3C4, and the remainder might arise lower.

The origin of the ICA commonly has a somewhat fusiform dilation,
known as the carotid bulb, comprising a rich network of neurofibers and
highly sensitive baroreceptors that exert control over peripheral
vascular tone and cardiac chronotropy.

The ECA supplies much of the extracranial head and facial circulation.

The external carotid artery and its branches have a broadly redundant
circulation and excellent arterial collaterals, so atherosclerosis or
impingement during ICA revascularization is usually of little clinical
consequence. Jaw or tongue claudication can occur if bilateral ECA
insufficiency exists.
The ICA typically courses posteriorly and laterally to the ECA.


It is divided into five segments before giving rise to the intracerebral
circulation. In ascending order, they are cervical, petrous, cavernous, clinoid,
and supraclinoid.

The cervical and petroussegments have no branches.

The ICA enters the cranial vault through the foramen lacerum in the petrous
bone.

Then, the ICA traverses the cavernous sinus with the abducens nerve and
supplies branches to the posterior pituitary artery via the
meningohypophyseal artery.

The ICA penetrates the dura mater in the supraclinoid segment.

Branches of the supraclinoid ICA include the ophthalmic artery, anterior
choroidal artery, and posterior communicating artery before terminating in the
anterior cerebral and middle cerebral arteries.

The Circle of Willis

The circle of Willis is an anastomotic network at the base
of the brain, surrounding the optic chiasm and the
pituitary stalk .

The posterior communicating artery (PCOM), arising
from the terminal portion of the supraclinoid ICA,
provides the major collateral connection between the
anterior circulation (from the ICA) and posterior
circulation (to the posterior cerebral artery).

Although the PCA typically arises from the basilar artery
of the posterior circulation, the PCA could arise directly
from the ICA, without any PCOM connection of the
anterior and posterior circulation. By definition, this is
known as fetal PCA.
Collaterals

From the external carotid artery to the internal carotid artery (via the
internal maxillary branch of the external carotid artery and the
superficial temporal artery to the ophthalmic branches of the internal
carotid artery).

From the external carotid artery to the vertebral artery (via the occipital
branch of the external carotid artery).

From the vertebrobasilar arterial system to the internal carotid artery
(via the posterior communicating artery), and

Between the left and right internal carotid arteries (via the
interhemispheric circulation through the anterior communicating
artery).

The configuration of the circle of Willis is also highly variable, with a
complete circle in fewer than 50% of individuals.

Normal Carotid Vascular Physiology

Compression or stretching of the carotid sinus can cause a vasovagal
(hypotension and bradycardia) or vasodepressor (hypotension without
bradycardia) response and systemic hypotension.
These responses are mediated via stimulation of the carotid sinus nerve
(a branch of the glossopharyngeal nerve) in the carotid baroreceptor,
and vagus nerve activation leading to inhibition of sympathetic tone.
The sensitivity of the carotid baroreceptors is variable and may be
affected by medications (e.g., vasodilators and beta-blockers might
increase sensitivity), the presence of calcified plaque in the carotid bulb
(increased sensitivity), or prior CEA (decreased sensitivity).

Pre-operative medication
The patient should be adequately hydrated as with
all vascular catheterisation procedures.

Aspirin and Clopidogrel need to be initiated at
least 24 hours prior to the procedure. A loading
dose of 300 mg of each is given if the patient is not
on them regularly, with 75 mg daily thereafter.

Anti-hypertensive medication is reviewed, and the
beta-blocker stopped for the day of the procedure.
The aim is to have a systolic pressure between
120180 mmHg at the start of the procedure.
CAROTID ANGIOGRAPHY
FA ACCESS, In case of diseased iliac arteries a 23 cm sheath
and in case of an abdominal aortic aneurysm a 40 cm sheath
may be preferred.

2000 UNITS HEPARIN

A pigtail is inserted into the ascending aorta for aortic arch
angiography.

LAO 40elongates the aortic arch and demonstrates the origin
of the great vessels.

40 ml, 20 ml/sec.
Carotid angiography contd
For selective angiography of the carotid and/or
vertebral arteries, the most commonly used catheters
are the Vitek, Berenstein , Sidewinder, Simmons,
Headhunter, Bentson and Mani catheters.

May use angled hydrophilic guide wire (i.e., Glidewire,
Terumo) to assist the catheter past the innominate
bifurcation and selectively into the right carotid.

One may take one cine run of the innominate
bifurcation in the RAO 40 projection to excluded
ostial carotid disease prior to engaging the carotid.
Carotid angiography contd
The usual camera angle of the right carotid
system is RAO 30 to 40 and RAO 90; this will
provide clear visual separation of the bifurcation of
the right internal and right external carotid artery.

For anterior cerebral circulation, RAO 90 and AP
cranial 30 (known as Townes View), are taken
of the whole skull.

Take care to record a prolonged cine to ensure
capture of the venous phase as well.
Carotid angiography contd
After all images of the right carotid system have been successfully recorded, the
catheter is disengaged and inserted into the left common carotid artery.

The usual angles for imaging the left carotid system are LAO 30 to 40, and
LAO 90; this allows separation of the bifurcation of the left internal and left
external carotid artery.

For anterior cerebral circulation, LAO 90 and AP cranial 30 are taken of the
entire skull, making sure to visualize the venous phase.

If the suspected target of intervention is the right carotid artery, it is
recommended to perform the angiography of the left carotid first to avoid
cannulating the right carotid artery twice.
CAROTID STENTING
Once the decision is made to proceed with carotid stenting,
intravenous anticoagulation is given. Angiomax (Bivalirudin)
and unfractionated heparin are most commonly used.

If heparin is used, the medication should be administered to
achieve an activated clotting time (ACT) greater than 200
seconds ( between 200-250).

The ACT is tested 5 minutes after heparin has been administered,
and every half hour thereafter, until the interventional portion of
the procedure has been completed.

Additional heparin may be needed to maintain the ACT
CAROTID STENTING

Additional Equipment needed for the interventional
portion of the procedure includes a guiding catheter or
90 cm guide sheath, embolic protection device, a self-
expanding stent, and an angioplasty balloon.

Depending on physician preference, a guide catheter
(An 8Fr guide usually a right coronary guide is
advanced into the ascending aorta over a hydrophilic
0.0035 wire) or 90 cm guide sheath long enough to
extend from the common femoral artery to the proximal
portion of the common carotid is used.

The diagnostic catheter is exchanged for the guiding
catheter or sheath with the use of a stiff exchange wire
with a very soft tip (a stiff Amplatz-type wire).
Strategies for emboli protection devices in carotid artery stenting. On the
left panel, a filter device is demonstrated; in the middle, a distal balloon
occlusive device; and in the right panel, a proximal occlusive device. CCA,
common carotid artery; ICA, internal carotid artery; ECA, external carotid
artery.
EMBOLIC PROTECTION DEVICES USED FOR CAROTID
ARTERY STENT (CAS) PROCEDURES


Distal protection is the most accepted technique currently.

The most commonly used devices are usually a steerable .014-inch
guide wire with a self-expanding filter basket at the end, designed to
capture any debris that may become dislodged from the lesion during
the intervention.

The distal protection device must be sized accurately.

If the device is sized too small for the carotid artery, the risk of debris
flowing past the basket resulting in transient cerebral ischemia or
infarction exists.

Correct placement of the basket is well distal to the target lesion,
preferably in a straight portion of the artery, allowing room to safely
pass the balloon and stent without the basket or wire moving during
exchanges.
Embolic protection device
FILTER
WIRE
Protection in Benign Lesion
is Worthwhile
Predilatation
Predilatation can be performed to ensure that a
stent delivery system can safely pass through the
stenosis.

Safe predilatation is done by undersizing the
artery; if the lumen of the artery is 6 mm in
diameter, the predilatation balloon should
measure about 4 mm.

The balloon is inserted over the distal protection
device wire.
Predilatation
If the lesion is tight, with less than a 2 mm
diameter, or looks calcified, the pre-dilatation with
a 3 mm 20 mm balloon is recommended.

Direct stenting may be performed for less severe
stenoses.

It is vital to give atropine 600 micrograms prior to
balloon inflation. Failure to do so will result is
bradycardia and hypotension which can be
difficult to manage and may be prolonged.

Choosing a stent
A closed cell design will improve lesion coverage if a lot of
debris is expected, but will not be as flexible as an open cell
design.

A stainless steel stent (Carotid Wallstent, Boston) is likely to
have more radial strength, but will not be as conformable as a
nitinol stent (e.g. Precise stent, Cordis, or Acculink, Guidant).

When choosing the stent, the size of the common carotid artery
proximal to the lesion, as well as the internal carotid artery
distal to the lesion, must be determined.

In regards to stent diameter, it is usually best to oversize the
stent. Oversizing by 12 mm compared to the vessel size
allows the stent to expand after postdilatation, decreasing the
risk of migration. For example, if the vessel is 6 mm, an 8 mm
stent is appropriate.


Choosing a stent
The length of the stent is chosen in the same way; if the
lesion length is 20 mm, a 30 or 40 mm stent is chosen.
The stent should extend past both the proximal and
distal portion of the lesion.

The role for tapered stents (designed to be smaller in
the ICA section than the CCA section) is not clear
(Acculink, Guidant).

Self-expanding stents are used almost exclusively.

It appears that stenting across the ECA origin does not
matter clinically. Since many ICA stenoses extend into
the carotid bifurcation, the norm is to stent into the CCA
from the ICA.


Indications for Use of Balloon Expandable
Stents
Covered Stents In The Carotids
Rupture
Dissection
Post CEA Pseudoaneurysm
Blunt Trauma
Penetrating Trauma
Stent deployment

When the stent is ready for deployment, it is
optimal to initially deploy only one-third of the
stent, and double check placement due to the
fact most self-expanding stents tend to jump
forward during deployment.

If satisfied with stent placement, the stent is
then fully deployed, and the delivery system is
removed.

Postdilatation
Postdilatation is performed to ensure proper
expansion of the stent and effectively dilate any
remaining plaque against the wall of the artery.

The size of the postdilatation balloon should be the
size of the vessel at the distal deployment edge of the
stent.

Post-dilatation is usually required to allow the stenosis
to be reduced to <2030%. There appears to be no
need to go for 0% as one might for the coronary, and
high pressure, large balloon inflation may lead to
unnecessary additional risk by causing more
embolisation.

Postdilatation
Before inflating the balloon, make sure that the staff are ready
and alert.

At this juncture, intravenous atropine sulfate can be given
prophylactically to maintain the heart rate and counter the blood
pressure drop normally seen during high-pressure balloon
inflation.

Intravenous fluids are open to the patient and prepped with a
pressure bag.

The balloon should be inflated quickly, monitoring both the
patients vital signs and the size of the balloon.

Once full expansion of the stent has been achieved, the balloon
is deflated immediately.
Before removing the balloon, angiography should be
performed to ensure that no perforation or dissection of the
vessel has occurred.

The balloon is then carefully removed, followed by the distal
protection device.

With all devices removed, a final set of angiograms is
performed in a minimum of two views.

Poststent cerebral angiography should also be performed to
ensure the patency of all vessels.

After the procedure the systolic blood pressure should be
below 140 mmHg. A lower pressure is preferable, especially
in case of a very tight lesion before stenting and/or in case of
a contralateral occlusion because these patients have a
higher risk of intracranial bleeding.
SUMMARY OF TECHNIQUE TO PERFORM CAROTID
ARTERY STENTING IN STANDARD CASES
Potential Complications of Carotid Artery Stenting

TAKE HOME MESSAGES
CAROTID ATHEROSCLEROTIC DISEASE IS HIGHLY
PREVALENT.

OPTIMIZED MEDICAL TREATMENT SHOULD ALWAYS BE
GIVEN.

CEA IS STILL GOLD STANDARD DEFINITIVE TREATMENT
ESP. IN LOW RISK PATIENT & IN EXPERT HANDS.

CAS IS AN ALTERNATIVE OPTION ESP. IN HIGH RISK
CASES.

CASE SELECTION & EXPERTISE IS KEY TO SUCCEESS OF
CAS.

DPDs SHOULD ALWAYS BE USED DURING CAS.
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