Transcript INTRODUCTION

Revascularisation in carotid artey stenosis
Journal Review
INTRODUCTION

The locations most frequently affected by carotid atherosclerosis
are the proximal internal carotid artery and the carotid
bifurcation.

Progression of atheromatous plaque at the carotid bifurcation
results in luminal narrowing, often accompanied by ulceration.

Leads to ischemic stroke or transient ischemic attack (TIA) from
embolization or thrombosis.
MANAGEMENT OF CAROTID STENOSIS

CAROTID ENDARTERECTOMY

CAROTID STENTING

MEDICAL MANAGEMENT
ASYMPTOMATIC CAROTID DISEASE
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CAROTID ENDARTERECTOMY

Randomized controlled trials have established that carotid
endarterectomy (CEA) is beneficial for patients with
asymptomatic internal carotid artery stenosis of 60 to 99 percent

The degree of benefit is not as good as for symptomatic carotid
stenosis

The evidence supporting CEA for asymptomatic carotid disease
is less for women than for men

Asymptomatic Carotid Atherosclerosis Study (ACAS)
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Asymptomatic Carotid Surgery Trial (ACST)
10-year stroke prevention after successful carotid
endarterectomy for asymptomatic stenosis (ACST)

Whether the addition of CE to aspirin plus risk factor
modifications will affect the incidence of TIA or infarctions in
patients with asymptomatic but haemodynamically significant
carotid stenosis .

This study randomly assigned patients during 1993-2003 to
immediate CEA or deferral of any carotid artery procedure until
a more definite indication was thought to have arisen, and
followed them up until 2006-08
Halliday A, Mansfield A, Marro J, et al. Prevention of disabling and fatal
strokes by successful carotid endarterectomy in patients without recent
neurological symptoms: randomised controlled trial.
Lancet 2004

126 centers in 30 countries participated.

Patients were eligible if:
(1) they had severe unilateral or bilateral carotid artery stenosis
(carotid artery diameter reduction at least 60%)
(2) this stenosis had not caused stroke, transient cerebral
ischaemia, or any other relevant neurological symptoms in the
past 6 months

A total of 3120 patients entered the study between April 1993,
and July 2003, with no significant differences in baseline
characteristics between those randomly allocated immediate
CEA and deferral.

560 patients were allocated immediate CEA versus 1560
allocated deferral of any carotid procedure.

Medication was similar in both groups throughout the study

Most were on antithrombotic and antihypertensive therapy.

Net benefits were significant, both for those on lipid-lowering
therapy and both for men and for women up to 75 years of age
at entry.

Successful CEA for asymptomatic patients younger than 75 years
of age reduces 10 year stroke risks.

Half this reduction is in disabling or fatal strokes.

For men and women younger than 75 years with asymptomatic
stenosis,successful carotid surgery is beneficial.
Endarterectomy for Asymptomatic Carotid
Artery Stenosis-ACAS Trial
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Objective
To determine whether the addition of carotid endarterectomy to
aggressive medical management can reduce the incidence of
cerebral infarction in patients with asymptomatic carotid artery
stenosis
Prospective, randomized, multicenter trial.
Thirty-nine clinical sites across the United States and Canada.
December 1987 to December 1993
Total of 1662 patients with asymptomatic carotid artery stenosis
of 60% or greater reduction in diameter were randomized
Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the
Asymptomatic Carotid Atherosclerosis Study. JAMA 1995

At baseline, recognized risk factors for stroke were similar
between the two treatment groups.

Intervention. Daily aspirin administration and medical risk
factor management for all patients; carotid endarterectomy for
patients randomized to receive surgery.

Main Outcome Measures
Any transient ischemic attack, stroke, or death occurring in the
perioperative period.

Results
After a median follow-up of 2.7 years, the aggregate risk over 5
years for ipsilateral stroke and any perioperative stroke or death
was estimated to be 5.1% for surgical patients and 11.0% for
patients treated medically (aggregate risk reduction of 53% [95%
confidence interval, 22% to 72%]).
Conclusion

Patients with asymptomatic carotid artery stenosis of 60% or
greater reduction in diameter will have a reduced 5-year risk of
ipsilateral stroke if carotid endarterectomy performed with less
than 3% perioperative morbidity and mortality is added to
aggressive management of modifiable risk factors
Degree of stenosis

Data regarding degree of stenosis and stroke risk in
asymptomatic carotid disease are conflicting

Major asymptomatic CEA trials (ACAS and ACST) have not
found a correlation between degree of stenosis and risk of stroke
for patients with asymptomatic 60 to 99 percent stenosis.
Lewis RF, Abrahamowicz M, Côté R, Battista RN. Predictive power of duplex
ultrasonography in asymptomatic carotid disease. Ann Intern Med 1997; 127:13.

The study analyzed the natural history of asymptomatic carotid
disease in 714 patients who had serial carotid ultrasound
examinations biannually for a mean follow-up of 3.2 years
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Progression to carotid stenosis of ≥80 percent was associated
with a significantly higher risk for cerebrovascular events and
death.
MEDICAL MANAGEMENT

Medical therapy that includes rigorous and compliant use of
statins and antiplatelet agents, along with treatment of
hypertension, cigarette smoking, and diabetes

Medical management may be a reasonable alternative to
endarterectomy in patients with asymptomatic carotid disease.
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A prospective population-based study identified 101 patients
with an asymptomatic ≥50 percent carotid stenosis who were
treated with intensive medical management.
Over a mean follow-up of three years, there was only one minor
ipsilateral stroke, for an average annual stroke rate of 0.34
percent (95% CI 0.1-1.87)
By comparison, ipsilateral annual stroke rates in patients assigned
to medical therapy in the major endarterectomy trials were
approximately 2 to 3 percent
Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of
ipsilateral stroke in patients with asymptomatic carotid stenosis
on best medical treatment: a prospective, population-based
study. Stroke 2010; 41:e11.
Spence JD, Coates V, Li H, et al. Effects of intensive medical therapy on
microemboli and cardiovascular risk in asymptomatic carotid stenosis. Arch
Neurol 2010; 67:180.
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A prospective study from a single tertiary center compared
treatment and outcome for two groups of patients with
asymptomatic carotid stenosis of ≥60 percent: 199 patients who
were enrolled from 2000 through 2002 and 269 patients who
were enrolled from 2003 through 2007

At baseline, a reduction in the proportion of patients with
intracranial microemboli detected by transcranial Doppler
ultrasound (12.6 versus 3.7 percent)

In the first year of follow-up, a lower rate of carotid plaque
progression (69 versus 23%) noted.

In the first two years of follow-up, a decrease in the composite
cardiovascular event endpoint of stroke, death, myocardial
infarction, or CEA after development of symptoms (17.6 versus
5.6 percent)
Stenting trials

Cochrane systematic review identified ten randomized controlled
trials with 3178 patients that compared CEA with CAS in
patients with symptomatic or asymptomatic carotid disease
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During long-term follow-up, the overall analysis found no
significant difference between CEA and CAS in the risk of
stroke or death
Stenting versus Endarterectomy for Treatment of
Carotid-Artery Stenosis-CREST
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Study Design
CREST is a randomized, controlled trial
108 centers in the United States and 9 in Canada.
Centers were required to have a team consisting of a neurologist,
an interventionist, a surgeon, and a research coordinator
Brott TG, Hobson RW 2nd, Howard G, et al. Stenting versus endarterectomy
for treatment of carotid-artery stenosis. N Engl J Med 2010; 363:11
Selection of Study Patients
Considered to be symptomatic if they had had
 a transient ischemic attack
 amaurosis fugax,
 minor nondisabling stroke involving the study carotid artery
within 180 days before randomization.
Eligibility criteria were
stenosis of 50% or more on angiography
70% or more on ultrasonography
70% or more on computed tomographic angiography or
magnetic resonance angiography
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
Eligibility was extended in 2005 to include asymptomatic
patients, for whom the criteria were stenosis of 60% or more on
angiography, 70% or more on ultrasonography, or 80% or more
on computed tomographic angiography or magnetic resonance
angiography.

Patients were excluded if they had had a previous stroke,chronic
atrial fibrillation, myocardial infarction within the previous 30
days, or unstable angina.
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At least 48 hours before carotid-artery stenting, patients received
aspirin, at a dose of 325 mg twice daily, and clopidogrel at a dose
of 75 mg twice daily.
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After the procedure, patients received 325-mg doses of aspirin
daily for 30 days and either clopidogrel, 75 mg daily, or
ticlopidine, 250 mg twice daily, for 4 weeks.
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At least 48 hours before carotid endarterectomy, patients
received 325 mg of aspirin daily and continued to receive that
dose for a year or more
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The primary end point was the composite of any stroke,
myocardial infarction, or death during the periprocedural period
or ipsilateral stroke within 4 years after randomization

From December 2000 through July 2008, a total of 2522 patients
were randomly assigned to one of the two treatments

Dyslipidemia was more common among patients in the
endarterectomy group than among those in the stenting group
(85.8% vs. 82.9%, P=0.048), more than 80% of patients had
severe stenosis
Primary End Point
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There was no significant difference in the estimated 4-year rates
of the primary end point between carotid-artery stenting and
carotid endarterectomy (7.2% and 6.8%, respectively; hazard
ratio for stenting, 1.11; 95% confidence interval 0.81 to 1.51;
P=0.51)
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During the periprocedural period, the incidence of the primary
end point was similar with carotid-artery stenting and carotid
endarterectomy (5.2 and 4.5%, respectively; hazard ratio for
stenting, 1.18; 95% CI, 0.82 to 1.68; P=0.38)

An interaction between age and treatment efficacy was detected
(P=0.02)
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Crossover noted at an age of approximately 70 years.
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Carotid-artery stenting show greater efficacy at younger ages,
and carotid endarterectomy at older ages.

Cranial-nerve palsies were less frequent during the
periprocedural period with carotid-artery stenting (0.3%, vs.
4.7% with carotid endarterectomy; hazard ratio, 0.07; 95% CI,
0.02 to 0.18).

CREST results indicate that carotid-artery stenting and carotid
endarterectomy were associated with similar rates of the primary
composite outcomes- periprocedural stroke, myocardial
infarction, or death and subsequent ipsilateral stroke — among
men and women with either symptomatic or asymptomatic
carotid stenosis.

The incidence of periprocedural stroke was lower in the
endarterectomy group than in the stenting group

The incidence of periprocedural myocardial infarction was lower
in the stenting group.
SAPPHIRE

The SAPPHIRE trial tested the hypothesis that CAS is not
inferior to CEA in patients considered at high risk for carotid
surgery who had either symptomatic or asymptomatic carotid
stenosis
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Randomly assigned 334 patients to either CAS or CEA; both
symptomatic patients with ≥50 percent carotid stenosis and
asymptomatic patients with ≥80 percent carotid stenosis by
angiography or ultrasound were enrolled.

More than 70 percent of patients had asymptomatic carotid
disease.

The stent used employed a distal embolic protection device
Yadav JS, Wholey MH, Kuntz RE, et al. Protected carotid-artery stenting
versus endarterectomy in high-risk patients.
N Engl J Med 2004; 351:1493

The primary end point of SAPPHIRE was the cumulative
incidence of a major cardiovascular event at one year, which
included a composite of periprocedural death, stroke, or
myocardial infarction (within 30 days after the procedure),
and/or death or ipsilateral stroke between 31 days and one year.

There was significant reduction in the primary composite end
point for CAS compared with CEA
(12.2 versus 20.1 percent, absolute difference 7.9 percent, 95%
CI -0.7 to 16.4 percent)

There was no significant difference in the major secondary end
point (ie, primary end point events plus death or ipsilateral stroke
between one and three years) for CAS compared with CEA (24.6
versus 26.2 percent)

CONCLUSION
CAS is not inferior to CEA in patients with asymptomatic disease
Stenting in specific subgroups
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Elderly patients appear to do worse with CAS than with CEA

In the prospective CREST trial, the rate of poor outcome in
patients age 70 and older was higher with stenting than with
endarterectomy.

In a meta-analysis of 41 studies of either CEA or CAS in patients
≥80 years old, the relative risks of death or myocardial infarction
at 30 days were similar for patients having CAS and CEA, but
the stroke rate was significantly higher for CAS (7.0 versus 1.9
percent) .

Pooled relative risk (RR) was more than three-fold higher for
stroke after CAS (RR 2.18 versus 0.63 with CEA)
Usman AA, Tang GL, Eskandari MK. Metaanalysis of procedural stroke and
death among octogenarians: carotid stenting versus carotid endarterectomy.
J Am Coll Surg 2009; 208:1124
PRACTICE GUIDELINES
Goldstein LB, Bushnell CD, Adams RJ, et al.
Guidelines for the primary prevention of stroke: a
guideline for healthcare professionals
American Heart Association/American Stroke
Association.
Stroke 2011; 42:517

Patients with asymptomatic carotid artery stenosis should be
screened for other treatable risk factors for stroke with
institution of appropriate lifestyle changes and medical therapy.

Selection of asymptomatic patients for carotid revascularization
should be guided by an assessment of comorbid conditions and
life expectancy, and should include a thorough assessment of
the risks and benefits of the procedure

The use of aspirin in conjunction with CEA is recommended
unless contraindicated.

Prophylactic CEA performed with <3 percent morbidity and
mortality can be useful in highly selected patients with an
asymptomatic carotid stenosis (minimum 60 percent by
angiography, 70 percent by Doppler ultrasound).

Prophylactic CAS might be considered in highly selected patients
with an asymptomatic carotid stenosis (≥60 percent on
angiography, ≥70 percent on Doppler ultrasonography, or ≥80
percent on CT angiography or MR angiography).

The usefulness of CAS as an alternative to CEA in asymptomatic
patients at high risk for the surgical procedure is uncertain.
SYMPTOMATIC CAROTID STENOSIS
DEFINITION OF SYMPTOMATIC
DISEASE

“Focal neurologic symptoms that are sudden in onset and
referable to the appropriate carotid artery distribution (ipsilateral
to significant carotid atherosclerotic pathology), including one or
more transient ischemic attacks characterized by focal neurologic
dysfunction or transient monocular blindness, or one or more
minor (nondisabling) ischemic strokes”
Beneficial effect of carotid endarterectomy in symptomatic patients with highgrade carotid stenosis. North American Symptomatic Carotid Endarterectomy
Trial Collaborators. N Engl J Med 1991; 325:445
Vertigo and syncope are not caused by carotid stenosis
The definition is includes only carotid symptoms within the
previous six months
NASCET trial
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NASCET was initiated in the mid-1980s
To investigate the efficacy of CEA compared with medical
treatment in patients with symptomatic carotid atherosclerotic
disease
Prospective, multi-center trial enrolled 659 patients who had had
a hemispheric or retinal TIA or a nondisabling stroke within the
120 days before entry and had stenosis of 70 to 99 percent in the
symptomatic (ipsilateral) carotid artery.
Beneficial effect of carotid endarterectomy in symptomatic patients with highgrade carotid stenosis. North American Symptomatic Carotid Endarterectomy
Trial Collaborators.
N Engl J Med 1991; 325:445.
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
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The study was prematurely terminated because of evidence that
surgery was beneficial in this selected group of patients
Patients followed up for a mean of 18 months
Significant benefits for CEA
 A lower risk of any stroke or death (15.8 versus 32.3 percent)
 A lower risk of any ipsilateral stroke (9 versus 26 percent)
 A lower risk of major or fatal ipsilateral stroke (2.5 versus
13.1 percent)
 A lower risk of any major stroke or death (8.0 versus 19.1
percent)
CONCLUSION

CEA was highly beneficial for patients with recent TIAs or
nondisabling strokes with ipsilateral stenosis of 70 to 99 percent
Randomised trial of endarterectomy for
recently symptomatic carotid stenosis: final
results of the MRC European Carotid Surgery
Trial (ECST)
To assess the risks and benefits of carotid endarterectomy,
primarily in terms of stroke prevention, in patients with recently
symptomatic carotid stenosis.
Multicentre, randomised controlled trial
Enrolled 3024 patients.
MRC European Carotid Surgery Trial: interim results for symptomatic
patients with severe (70-99%) or with mild (0-29%) carotid stenosis.
European Carotid Surgery Trialists' Collaborative Group. Lancet 1991

Enrolled men and women of any age, who within the previous 6
months had had at least one transient or mild symptomatic
ischaemic vascular event in the distribution of one or both
carotid arteries.

Between 1981 -1994, allocated 1811 (60%) patients to surgery
and 1213 (40%) to control

Follow-up was until the end of 1995 (mean 6·1 years), and the
main analyses were by intention to treat.
Findings

The overall outcome (major stroke or death) occurred in 669
(37·0%) surgery-group patients and 442 (36·5%) control-group
patients.

The risk of major stroke or death complicating surgery (7·0%)
did not vary with severity of stenosis.

The risk of major ischaemic stroke ipsilateral to the unoperated
symptomatic carotid artery increased with severity of stenosis,
particularly above about 70—80% of the original luminal
diameter .

The immediate risk of surgery was worth taking against the
long-term risk of stroke without surgery when the stenosis was
greater than about 80% diameter
Interpretation

Carotid endarterectomy is indicated for most patients with a
recent non-disabling carotid-territory ischaemic event when the
symptomatic stenosis is greater than about 80%
Timing of surgery

After mild stroke or TIA — A pooled analysis of the NASCET
and the ECST trials,found that CEA within two weeks of a
nondisabling stroke or TIA significantly improved outcomes
compared with later surgery

In the subgroup of patients with 70 percent or greater carotid
stenosis, CEA was associated with a 30.2 percent reduction in
absolute risk of stroke in patients randomized within two weeks
of their last event
Rothwell PM, Eliasziw M, Gutnikov SA, et al. Sex difference in the effect of time
from symptoms to surgery on benefit from carotid endarterectomy for transient
ischemic attack and nondisabling stroke. Stroke 2004; 35:2855
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For patients with 50 to 69 percent stenosis, clinically important
benefits from CEA were noted only in patients randomized
within two weeks of their last event
The decline in benefit of CEA over time was more rapid in
women than in men.
Surgical benefit in women was confined to those who had CEA
within two weeks after their last event, irrespective of the degree
of stenosis.
CEA within two weeks of a nondisabling hemispheric stroke was
not associated with an increased operative risk

After moderate to severe stroke
The benefit of CEA for patients with moderate to severe
ischemic stroke has not been evaluated in randomized clinical
trials, as patients who have disabling stroke were not eligible for
NASCET or ECST.
Emergency CEA for progressing/fluctuating
stroke or crescendo TIA

A 2009 systematic review identified 47 nonrandomized studies of
CEA for recently symptomatic carotid stenosis that reported
data on time from presenting event to CEA
(including 18 studies that stratified emergent and nonemergent
CEA. )

The rate of perioperative stroke or death was significantly higher
with emergent CEA (14 versus 4 percent for nonemergency
CEA)
Rerkasem K, Rothwell PM. Systematic review of the operative risks of carotid
endarterectomy for recently symptomatic stenosis in relation to the timing of
surgery. Stroke 2009; 40:e564.
Gender

Benefit of CEA may be greater for men than for women

The risk of stroke ipsilateral to a symptomatic carotid stenosis is
significantly lower for medically treated women than men, while
the perioperative risk of death from CEA is significantly higher
in women than in men.

CEA is beneficial for women with 70 to 99 percent symptomatic
carotid stenosis, and the five-year absolute risk reduction in
stroke is similar for men and women
CEA is not beneficial for most women with 50 to 69
percent symptomatic carotid stenosis
Rothwell PM, Eliasziw M, Gutnikov SA, et al. Endarterectomy for symptomatic
carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet
2004; 363:915.
Alamowitch S, Eliasziw M, Barnett HJ, et al. The risk and benefit of
endarterectomy in women with symptomatic internal carotid artery disease.
Stroke 2005; 36:27
Contralateral carotid stenosis or occlusion

CEA is likely to be beneficial for patients who have symptomatic
ipsilateral carotid stenosis and coexisting severe contralateral
carotid stenosis or occlusion.

They are at higher perioperative risk than those without a severe
contralateral carotid artery stenosis.
Gasecki AP, Eliasziw M, Ferguson GG, et al. Long-term prognosis and effect of
endarterectomy in patients with symptomatic severe carotid stenosis and
contralateral carotid stenosis or occlusion: results from NASCET. North
American Symptomatic Carotid Endarterectomy Trial (NASCET) Group.
J Neurosurg 1995; 83:778

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Medically treated patients with an occluded contralateral carotid
were twice likely to have an ipsilateral stroke compared with
those with severe or mild to moderate disease (hazard ratio 2.36
and 2.65).
Among surgically treated patients, the perioperative risk of
stroke and death was higher in those with a totally occluded or
mild to moderately stenotic contralateral vessel (4 and 5 percent,
respectively) compared with those without contralateral disease.
Patients who had CEA had a significantly better outcome than
patients treated medically.
CAROTID STENTING
ICSS trial (CAVATAS 2)

1713 adults (age >40 years) with symptomatic carotid artery
stenosis were randomly assigned to treatment with either CEA
or CAS

All patients had carotid stenosis that was >50 percent by
noninvasive imaging such as duplex ultrasound.
International Carotid Stenting Study investigators, Ederle J, Dobson J, et al.
Carotid artery stenting compared with endarterectomy in patients with
symptomatic carotid stenosis (International Carotid Stenting Study): an
interim analysis of a randomised controlled trial. Lancet 2010; 375:985
Interim analysis at 120 days



The proportion of patients who reached the combined endpoint
of stroke, death, or myocardial infarction was significantly higher
for the stenting group than the endarterectomy group (8.5 versus
5.2 percent, hazard ratio 1.69, 95% CI 1.16-2.43)
The stenting group also had significantly higher rates for the
endpoints of any stroke (7.7 versus 4.1 percent), any stroke or
death (8.5 versus 4.7 percent), and all cause death (2.3 versus 0.8
percent)
There was no significant difference between the stenting and
endarterectomy groups for the endpoint of disabling stroke
(4.0 versus 3.2 percent)

A subanalysis of 231 patients in the ICSS -brain MRI found that
the proportion of patients with new ischemic brain lesions on
diffusion-weighted MRI at a median of one day after treatment
was significantly higher in the stenting group than in the
endarterectomy group (50 versus 17 percent, odds ratio 5.2, 95%
CI 2.8-9.8)

International Carotid Stenting Study investigators, Ederle J, Dobson J,
et al. Carotid artery stenting compared with endarterectomy in patients with
symptomatic carotid stenosis (International Carotid Stenting Study): an
interim analysis of a randomised controlled trial.
Lancet 2010; 375:985.
Bonati LH, Jongen LM, Haller S, et al. New ischaemic brain lesions on
MRI after stenting or endarterectomy for symptomatic carotid stenosis: a
substudy of the International Carotid Stenting Study (ICSS).
Lancet Neurol 2010; 9

SPACE

The SPACE trial was a multicenter European study designed to
test the hypothesis that CAS is not inferior to CEA for the
treatment of severe symptomatic carotid stenosis

Assigned 1183 patients to either CAS or CEA

Excluded high-risk patients with uncontrolled hypertension or
severe concomitant disease and recurrent carotid stenosis after
surgery or stenting.
SPACE Collaborative Group, Ringleb PA, Allenberg J, et al.
30 day results from the SPACE trial of stent-protected angioplasty versus
carotid endarterectomy in symptomatic patients: a randomised non-inferiority
trial.
Lancet 2006; 368:1239.



At 30 days - no significant difference between CAS and CEA in
the primary composite outcome measure, death or ipsilateral
ischemic stroke (6.8 versus 6.3 percent
No statistically significant difference between CAS and CEA in
the composite endpoint of any periprocedural stroke or death
and ipsilateral ischemic stroke up to two years after the
procedure
Recurrent carotid stenosis ≥70 percent was significantly more
frequent in the CAS group

Use of embolic protection devices with stenting was optional

Used in only 27 percent of patients treated with CAS .

No significant difference in the primary outcome of death or
ipsilateral ischemic stroke at 30 days between patients treated
with and without embolic protection
(7.3 and 6.7 percent, respectively, 90% CI 0.53-2.25).
EVA-3S



Hypothesis - CAS is not inferior to CEA for the treatment of
severe symptomatic carotid stenosis
Randomly assigned 527 patients with this condition to CAS or
CEA.
The study excluded high-risk patients with unstable angina,
uncontrolled diabetes, or uncontrolled hypertension, and patients
with previous carotid revascularization ( recurrent carotid
stenosis).
Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in
patients with symptomatic severe carotid stenosis.
N Engl J Med 2006



The incidence of any stroke or death at 30 days, the composite
primary outcome measure, was significantly higher with stenting
than with CEA (9.6 versus 3.9 percent, relative risk 2.5, 95% CI
1.2-5.1).
The trial was stopped prematurely due to an excess number of
deaths in the CAS group.
The prespecified main secondary outcome (any periprocedural
stroke or death and any non-periprocedural ipsilateral stroke
occurring in up to four years of follow-up) was also significantly
higher with stenting than with CEA (11.1 versus 6.2 percent,
hazard ratio 1.97, 95% CI 1.06-3.67) .

The risk of ipsilateral stroke after the periprocedural period was
low, and similar in both treatment groups.

The main criticism of EVA-3S -heterogeneity of operator
experience, stent types
(Interventional clinicians were required to have performed only
two stenting procedures with any new device before its use in
EVA-3S,five different stents and seven different protection
devices were used in the trial )
CREST

A secondary analysis showed that for the subgroup of patients
with symptomatic carotid disease, the periprocedural rate of
stroke and death was significantly higher for those assigned to
stenting compared with endarterectomy
(6.0 versus 3.2 percent, HR 1.89, 95% CI 1.1-3.2)
Effect of age


2010 meta-analysis of the three largest trials of patients with
symptomatic carotid disease (ICSS, EVA-3S, and SPACE)estimated risk of stroke or death for patients age 70 and older
was approximately two-fold higher for the carotid stenting group
compared with the endarterectomy group (103 of 856 versus 51
of 865 [12.0 versus 5.9 percent], risk ratio 2.04, 95% CI 1.48—
2.82) .
The estimated risk of stroke or death for patients age 69 and
younger was similar for the carotid stenting and endarterectomy
groups (50 of 869 versus 48 of 843 [5.8 versus 5.7 percent], risk
ratio 1.00, 95% CI 0.68—1.47).
Carotid Stenting Trialists' Collaboration, Bonati LH, Dobson J, et al. Shortterm outcome after stenting versus endarterectomy for symptomatic carotid
stenosis: a preplanned meta-analysis of individual patient data. Lancet 2010;
376:1062.

CREST trial- the rate of adverse events in patients age 70 and
older was significantly higher with stenting than with
endarterectomy
MEDICAL MANAGEMENT

These therapies include aggressive treatment with statins,
antiplatelet agents, and antihypertensive agents

Statin treatment can also reduce the incidence of first and
recurrent stroke.

Guidelines issued in 2011 by the AHA/ASA recommend
optimal medical therapy for all patients with carotid artery
stenosis and a TIA or stroke, including antiplatelet therapy, statin
therapy, and risk factor modification
Embolic protection devices
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Subdivided into distal and proximal types.
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Distal EPDs are more commonly used
Embolic protection device
Distal devices
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Devices that occlude or filter distal blood flow are designed to
catch debris dislodged during stent placement.
Deploy distal filters or balloons
Disadvantages
 They must pass across the stenosis-may dislodge emboli.
 Tight lesions may require predilatation before the distal
device can be placed.
 The presence of the EPD in the distal carotid artery may
induce vasospasm that can severely narrow the outflow and
cause stroke if prolonged.
 Distal EPDs may cause complications related to vessel wall
injury or to difficulty with removal of the distal device itself
Proximal devices
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Deploy occlusion balloons in the external carotid artery and the
common carotid artery
Following stent insertion, the proximal internal carotid artery is
suctioned to remove debris prior to deflating the occlusion
balloon
Disadvantages
 They are larger than distal devices.
 Cerebral ischemia may occur
 Injury to the common and external carotid arteries may occur
with balloon inflation
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Benefit from EPDs has not been established in randomized
controlled trials
Data from existing randomized controlled trials suggest that
EPDs are not effective for preventing symptomatic stroke or
new ischemic brain lesions on MRI
(butconclusion is based upon subgroup analyses with relatively
small numbers of patients and events)
Mas JL, Chatellier G, Beyssen B, et al. Endarterectomy versus stenting in
patients with symptomatic severe carotid stenosis. N Engl J Med 2006;
355:1660.
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A prespecified subgroup analysis of patients assigned to CAS in
the SPACE trial showed no significant difference in the 30-day
outcome of ipsilateral stroke or death between those who were
treated with (n = 151) or without (n = 416) embolic protection
(7.3 and 6.7 percent, respectively)
SPACE Collaborative Group, Ringleb PA, Allenberg J, et al. 30 day results
from the SPACE trial of stent-protected angioplasty versus carotid
endarterectomy in symptomatic patients: a randomised non-inferiority trial.
Lancet 2006; 368:1239.
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A 2007 meta-analysis, with data available from two randomized
trials, found no significant difference for the combined endpoint
of death or any stroke comparing treatment with or without
cerebral protection (odds ratio 0.77, 95% CI 0.41-1.46)
Ederle J, Featherstone RL, Brown MM. Percutaneous transluminal
angioplasty and stenting for carotid artery stenosis.
Cochrane Database Syst Rev 2007
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A systematic literature review of observational studies published
in 2008 reported 700 patients who had CAS with MRI data
available .
The rate of new ipsilateral DWI lesions on diffusion weighted
MRI was lower for CAS procedures using an EPD compared
with those done without an EPD (33 versus 45 percent)
Schnaudigel S, Gröschel K, Pilgram SM, Kastrup A. New brain lesions after
carotid stenting versus carotid endarterectomy: a systematic review of the
literature.
Stroke 2008; 39:1911.
Many prospective stent registries and case series show that the
periprocedural risk of stroke after CAS is significantly lowered
with the use of an EPD.
Brown MM. Carotid artery stenting--evolution of a technique to rival carotid
endarterectomy.
Am J Med 2004; 116:273.
Theron JG, Payelle GG, Coskun O, et al. Carotid artery stenosis: treatment
with protected balloon angioplasty and stent placement.
Radiology 1996; 201:627.
PRACTICE GUIDELINES
Goldstein LB, Bushnell CD, Adams RJ, et al.
Guidelines for the primary prevention of stroke: a
guideline for healthcare professionals
American Heart Association/American Stroke
Association.
Stroke 2011; 42:517
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For patients with recent TIA or ischemic stroke within the past
six months and ipsilateral severe (70 to 99 percent) carotid artery
stenosis, CEA is recommended if the perioperative morbidity
and mortality risk is estimated to be <6 percent.
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For patients with recent TIA or ischemic stroke and ipsilateral
moderate (50 to 69 percent) carotid stenosis, CEA is
recommended depending on patient-specific factors, such as age,
sex, and comorbidities, if the perioperative morbidity and
mortality risk is estimated to be <6 percent.
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When the degree of stenosis is <50 percent, there is no
indication for carotid revascularization by either CEA or CAS.
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When CEA is indicated for patients with TIA or stroke, surgery
within two weeks is reasonable rather than delaying surgery
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CAS is indicated as an alternative to CEA for symptomatic
patients at average or low risk of complications associated with
endovascular intervention when the diameter of the lumen of the
internal carotid artery is reduced by >70 percent by noninvasive
imaging or >50 percent by catheter angiography.
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CAS may be considered among patients with symptomatic severe
stenosis (>70 percent) in whom
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stenosis is difficult to access surgically
medical conditions are present that greatly increase the risk for
surgery
radiation-induced stenosis
restenosis after CEA.
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