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rates of TIAs, minor strokes, major strokes, and mortality were
2.6%, 2.5%, 1.4%, and 0.8%, respectively.
nical failures were usually related to inability to access the CCA
(2%-7% of patients), and prolonged procedural time was associated with increased morbidity.
patients at high surgical risk were encouraging; rates of adverse
CH
outcomes were comparable to standard CEA risk patients treated
32
with surgery.
96
87
It was noted that tech-
These results in a large series of
Box 32-5 Clinical and Anatomical Characteristics
Used to Define Patients at High
Endarterectomy Risk in the NASCET and
ACAS Trials
Anatomical
Significant lesion cranial to the body of the second cervical vertebrae
Previous ipsilateral endarterectomy
Results of Carotid Stenting Using
Embolic Protection
Periprocedural neurological events related to embolization during carotid arterial stent placement were not unexpected. In an
effort to reduce the incidence of these adverse events, transcranial Doppler studies were performed to investigate which stages
of the procedure were responsible for microemboli. Few particles
are released during sheath placement, with a modest number during wire crossing and predilation. The majority of particles were
found to be released from the atheromatous plaque during stent
deployment and the postdilation procedure.
sisted of plaque debris, fibrin and platelet aggregates, lipid vacuoles, and calcium fragments.
31,97
These findings provided the basis
64
The fragments con-
for development and routine use of embolic protection systems
during carotid stenting.
Carotid Stenting in High-Risk Carotid
Endarterectomy Patients
In 1998, the Stroke Council of the AHA published a series of recommendations relating to the performance of CEA in patients with
extracranial bifurcation carotid artery stenosis.
dations were based largely on the results of ECST,
80
ACAS.
These three large randomized clinical trials established the
benefit of CEA over prevailing best medical treatment and have provided much of the evidence base for current treatment of carotid
artery disease. The AHA Stroke Council recommended surgical revascularization in symptomatic (prior symptoms of a nondisabling
stroke or TIA) patients with more than 70% carotid stenosis, provided
the perioperative risk of stroke and death is less than 6%. In patients
with more than 60% stenosis without prior symptoms (asymptomatic
group), the recommendation for revascularization is valid provided
the perioperative risk of stroke and death is less than 3% and the
patient has a life expectancy of at least 5 years.
98
These recommen-
7
NASCET,3 and
Comorbidities
Age 80 years or older
History of renal, cardiac, or hepatic failure
Life expectancy less than 5 years
ACAS, Asymptomatic Carotid Atherosclerosis Study; NASCET, North American
Symptomatic Carotid Endarterectomy Trial.
To minimize potential confounding variables, such as conditions
known to increase the risk of operative treatment, patients in the
NASCET and ACAS studies were carefully selected, and those who
were regarded as high surgical (CEA) risk were excluded.
Box 32-5
lists anatomical characteristics and comorbidities that were used
to define high CEA risk. In the NASCET study, contralateral occlusion was not excluded, and 30-day risk of stroke and death in
this cohort was 9.4% (≈2.2 times the risk without this problem).
Excluding the SAPPHIRE study (see below), surgical outcomes
in high–CEA risk patients have never been tested in a large multicenter prospective trial with independent neurological assessment
and event adjudication, rendering conclusions about benefit of the
procedure in this population less clear.
During the initial investigation of CAS with embolic protection
as a therapeutic alternative to CEA, the target population included
patients who were high risk for CEA. These clinical trials were
designed using a nonrandomized registry format. Since the FDA
considers each carotid stent and embolic protection system as a
unique device set, each with its own risk profile, as a condition
of marketing (PMA) approval, every manufacturer was required
to perform its own separate study. This regulatory requirement
explains why so many “CEA high-risk registries”
all of which enrolled the same target population (
73,99–103
were formed,
Table 32-5) .
The study design, study hypothesis, and statistical approach were
largely similar for all the registries. The goal was to determine
whether outcomes in high-risk surgical patients treated with the
particular sponsor's stent in conjunction with its EPD was less than
or equal to that of objective performance criteria (OPC) derived
from historical controls undergoing surgical intervention with CEA.
6
TABLE 32-5 Published Outcomes from High Carotid Endarterectomy Risk Registries*
TRIAL
SAPPHIRE 2002 Cordis Smart/Precise Angioguard NA 6.90% 71.2%
ARCHeR 2003 Abbott Acculink Accunet 2.90% 8.30% 76.2%
SECuRITY 2003 Abbott Xact Emboshield 3.00% 7.20% NA
BEACH 2003 Boston Wallstent Filterwire EZ 2.50% 5.40% 76.7%
MAVErIC 2004 Medtronic AVE GuardWire 3.00% 5.40% NA
CAPTURE 2006 Abbott Acculink Accunet 2.60% 6.10% 86.2%
EXACT 2007 Abbott Xact Emboshield 1.80% 4.60% 90.1%
EMPiRE 2008 Gore Not specified Gore Flow Reversal 1.60% 3.70% 68%
CAPTURE 2 2009 Abbott Acculink Accunet 1.40% 3.50% 86.9%
PROTECT 2009 Abbott Xact Emboshield 0.50% 2.30% NA
CHOICE Ongoing Abbott Xact/Acculink Emboshield/Accunet 1.80% 3.90% NA
*The first of these began enrolling patients in 2000 and were largely completed by 2008.
MI, myocardial infarction, NA, not available.
YEAR
LAST PATIENT
ENROLLED
SPONSOR
STENT
EMBOLIC
PROTECTION DEVICE
DEATH/MAJOR
STROKE RATE
DEATH/
STROKE/MI
RATE
ASYMPTOMATIC
An OPC of 15% for patients with comorbidities and 11% for patients
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with anatomical risk factors was negotiated a priori and agreed to
by the FDA.
The SAPPHIRE
101
study was the only one that included a randomized arm (CAS vs. stent). This multicenter noninferiority randomized
study was conducted in 29 centers across the United States, and
results were published in 2004.
101
The study enrolled symptomatic
patients (≥50% stenosis on duplex ultrasound, 29% of the patient
population) and asymptomatic patients (≥80% stenosis on duplex
ultrasound), and the primary endpoint was defined as the cumulative incidence of death, stroke, and MI within 30 days of treatment, or
death and ipsilateral stroke between day 31 and 1 year from the time
of the procedure. Although the inclusion criteria included high–CEA
risk patients, prior to randomization, all members of the investigative team (neurologist, vascular or neurosurgeon, and interventionalist) had to agree that the patient was a suitable candidate for either
endarterectomy or stenting. If the surgeon assessing the patient concluded that endarterectomy could not be safely performed, but
the interventional physician judged that stenting was feasible, the
patient was not randomized, but instead was entered into a stent registry (n = 406). Likewise, if the surgeon deemed the patient suitable
for surgery, but the interventional physician did not think stenting
was feasible, the patient was entered into a surgical registry (n = 7).
Between August 2000 and July 2002, 747 patients were enrolled
in the study, and 334 patients underwent randomization. Of the 167
patients randomly assigned to stenting, 159 received the assigned
treatment. Of the 167 patients assigned to surgery, 151 received
the assigned treatment. All 334 patients were followed. Patients
undergoing CAS received the nitinol self-expanding Precise stent
and the AngioGuard filter-type EPD (Cordis/Johnson & Johnson,
Bridgewater, N.J.). In early 2002, the pace of enrollment abruptly
slowed because several carotid stent registries (nonrandomized)
had become available. The trial was therefore terminated because
of the decrease in enrollment, and the primary endpoint was analyzed with respect to the noninferiority of CAS compared with CEA,
using interval-censored survival data at 1 year.
By intention-to-treat analysis, the primary endpoint at 1 year
occurred in 20 CAS patients (12.2%) and 32 CEA patients (20.1%);
P = 0.05. Cranial nerve injuries were seen in 5% of the patients
undergoing CEA. The investigators concluded that carotid stenting
with embolic protection was not inferior to CEA in a high surgical risk population. The durability of carotid stenting in this patient
group (durability refers to the procedure's ability to prevent stroke,
not the need for repeat intervention due to restenosis) has been
supported by the 3-year follow-up data, which demonstrated that
there was no significant difference in long-term outcomes between
patients who underwent CAS using an EPD and those who underwent endarterectomy.
104
Post-approval Registries
As part of the condition for marketing approval of its devices
(stents and EPDs), the sponsor, Abbott Vascular, agreed to perform
FDA-mandated post-approval studies to assess the occurrence of
rare and unanticipated device-related events. These post-approval
studies have also provided an opportunity to assess the outcomes
of carotid stenting in high–CEA risk patients in the non-trial setting (real world). In 2009, Gray et al.73 reported the outcomes of
two such prospective multicenter (280 U.S. sites, 672 operators)
post-market surveillance studies involving CAS with distal embolic
protection using filters in high–CEA risk patients. These studies had
pre- and postprocedure neurological evaluation and independent
adjudication of neurological events. Results of these two studies, as
well as the outcomes of an earlier large (n = 4225) post-approval
study (CAPTURE),
In summary, key outcomes from the CAPTURE 2 and EXACT data
73
sets
are:
l 30-day death and stroke: 6.4% (95% confidence interval [CI],
102
are summarized in Table 32-6.
4.8%-8.4%) in the combined symptomatic population and 3.2%
(95% CI, 2.8%-3.7%) for the combined asymptomatic population.
l 30-day death and major stroke: 1.5% (95% CI, 1.2%-1.8%) for
the combined population and 2.6% (95% CI, 1.6%-4.0%) and
1.3% (95% CI, 1.0%-1.6%) for the combined symptomatic
and asymptomatic groups, respectively.
l In subjects with anatomical features unfavorable for surgery,
independent of age:
l Symptomatic (n = 60): 30-day death and stroke rate was 1.7%
(95% CI, 0.0%-8.9%; the single stroke was adjudicated as major).
l Asymptomatic (n = 371) 30-day death and stroke rate was
2.7% (95% CI, 1.3%-4.9%; 78% of strokes were minor).
l In the cohort of patients identified with physiological factors
unfavorable for surgery, the combined 30-day rate of death and
stroke for 574 symptomatic patients was 6.4% (95% CI, 4.6%-
8.8%), and for the 4603 asymptomatic patients was 3.3% (95%
CI, 2.8%-3.9%).
Operator Experience
In a recent publication, the CAPTURE 2 study investigators
lyzed the carotid stenting outcomes of 3388 patients (representing 64% of the total number of patients) to determine whether
physician or site-related variables affected outcomes of CAS.
Symptomatic patients and patients older than 80 years of age (two
known predictors of adverse outcomes) were excluded. During a
3-year interval between March 2006 and January 2009, 459 operators treated the study population in 180 U.S. hospitals. The composite rates of death, stroke, and MI, and the composite rates of death
and stroke at 30 days were 3.5% and 3.3%, respectively, for the full
CAPTURE 2 study cohort and 2.9% and 2.7%, respectively, for the
asymptomatic nonoctogenarian subgroup.
Two thirds of the sites (118 of 180 [66%]) had no death or stroke
events. Within the remaining sites, an inverse relationship between
adverse event rates and hospital patient volume as well as individual
operator volume was observed. The death and stroke rates trended
lower for interventional cardiologists compared with other specialties.
Similar conclusions were drawn from a German registry analysis
and a recent meta-analysis of published studies.
107
The CAPTURE 2
study authors concluded that both site and operator volume were the
most important determinants of perioperative events, and defined a
threshold of 72 cases for consistently achieving a 30-day death and
stroke rate of less than 3%. This 72 case number is higher than the
entry threshold for operators participating in randomized trials like
CREST or ACT I (Carotid Stenting vs. Surgery of Severe Carotid Artery
Disease and Stroke Prevention in Asymptomatic Patients) trials.
105
ana-
106
Analysis and Critique
The analysis and critique that follows should be interpreted bearing in mind the limitations imposed by subset analysis and small
numbers of patients within these subsets.
405
CH
32
CAROTID ARTERY STENTING
TABLE 32-6 Postapproval Surveillance Studies
STUDY ENROLLMENT N SYMPTOMATIC ASYMPTOMATIC STENT EMBOLIC PROTECTION DEVICE
CAPTURE
CAPTURE 2
73
EXACT
102
73
2004-2006 3500 483 (14%) 3017 (86%) Acculink Accunet
2006-enrolling 4175 548 (13%) 3627 (87%) Acculink Accunet
2005-2007 2145 213 (10%) 1931 (90%) Xact Emboshield
406
SAPPHIRE (2002)
With the exception of SAPPHIRE, all other studies dealing with
carotid stenting in high–CEA risk patients were registry studies.
Despite the registry label, it should be noted that the high-risk CAS
registries were performed under FDA-scrutinized clinical protocols, with prospective data collection and event adjudication. The
importance of prospective independent clinical review was dem-
CH
onstrated by Rothwell and Warlow
32
rates following CEA. They found a threefold difference in neurological events between operator self-reported and independent
neurologist-assessed events. Both NASCET and ACAS used such
prospective independent evaluations.
Individually and collectively, a large number of patients,
mainly asymptomatic, have been studied within the context of
these registry trials and provide a robust data set for analysis
of high–CEA risk patients undergoing carotid stenting in the
United States. Cumulatively, a total of more than 10,000 patients
were included and analyzed in the three postmarketing studies
(90% asymptomatic), and analysis of the data has helped provide answers to important questions concerning carotid stenting in a real-world setting.
Carotid stenting outcomes have shown a steady and continuous improvement since the initial introduction of these devices
in U.S. trials (
Fig. 32-19). For example, compared with outcomes in
the ARCHeR and the original CAPTURE registries, the combined
results of the CAPTURE 2 and EXACT studies showed improvement
(30-day death and stroke: 6.9% vs. 5.7% vs. 3.6%, respectively), and
these improved outcomes meet AHA guidelines in the younger
than 80 years age group. As will be discussed later, in the CREST
study, the majority of neurological events were minor strokes, with
substantial if not complete resolution of the neurological deficits
during the follow-up period.
9%
8%
7%
6%
5%
4%
3%
2%
1%
0%
BEACH (2003)
ARCHeR (2003)
SECuRITY (2003)
FIGURE 3219 Published adverse event rates for carotid artery stent
studies and registries over the past 10 years. Note progressive decline in
events over time. The year in brackets is the time of last patient enrollment.
MAVErIC (2004)
CAPTURE (2006)
108
investigating adverse event
EXACT (2007)
EMPiRE (2008)
PROTECT (2009)
CAPTURE 2 (2009)
Death/major
stroke
Death/stroke/
MI
CHOICE (2011)
Several factors contributed to the improvement in the results
of carotid stenting. First is recognition of the clinical features that
define the high–stent risk patient. This was not appreciated at
the time when these registry studies were initiated. As operators
became more experienced, these high–stent risk patients were
excluded from studies initiated later in the decade with corresponding better outcomes.
Second, the pool of qualified experienced operators has
expanded with time, with corresponding improvement in outcomes. Moreover, there have been improvements in the devices. For
example, the profile of the EPDs has become smaller, and a variety
of nitinol stents specifically for use at the carotid bifurcation have
been developed. Improvements in technology, along with minor
adjustments in the procedure protocol (e.g., limiting post inflation
to a single inflation), have likely contributed to improved outcomes.
As a result, CAS outcomes in non-octogenarian, high–surgical
risk patients, both symptomatic and asymptomatic, are within the
acceptable thresholds of AHA standards. Additionally, in patients
deemed high CEA risk due to unfavorable anatomical features, the
outcomes meet AHA guidelines in both symptomatic and asymptomatic patients irrespective of age.
The higher event rates in the early (pre-2005) high risk CEA
carotid stent registries (i.e., event rates that breached the AHA
thresholds) is one likely explanation for lack of Centers for
Medicare and Medicaid Services (CMS) reimbursement for asymptomatic patients undergoing carotid stenting, despite FDA approval
for this indication in 2004. The outcomes of the CAPTURE 2 and the
EXACT post-marketing registries are compelling because at least
in the non-octogenarian high–CEA risk population, both symptomatic and asymptomatic (
Table 32-7), the death and stroke out-
comes were within the AHA guidelines.
The octogenarian and older population continues to be a challenge, and the decision to recommend and perform carotid stenting, especially in the asymptomatic patient older than 80 years of
age, has to be individualized.
Carotid Stenting in Symptomatic
Standard-Risk Patients
The introduction of CAS into clinical practice as an alternative to
CEA has required the completion of randomized trials to evaluate its efficacy and safety. In patients with symptomatic carotid
disease, there are four completed large, multicenter randomized controlled trials. These include the Endarterectomy versus
Angioplasty in Patients with Symptomatic Severe Carotid Stenosis
(EVA-3 S) trial,41 the Stent-Supported Percutaneous Angioplasty
of the Carotid Artery versus Endarterectomy (SPACE) trial,
International Carotid Stenting Study (ICSS),
109
and CREST.39 Since
the CREST study also included asymptomatic patients, it is discussed separately. Although the results from these individual trials
remain a source of controversy, the results are broadly similar and
have enabled the publication of guidelines by national societies.
EVA-3 S,41 a non-inferiority study, was conducted in 30 centers
across France and recruited and randomized usual (standard-risk)
CEA patients. These patients were within 120 days of either a TIA or
40
the
TABLE 32-7 Postapproval Surveillance Studies Outcomes
CAPTURE Symptomatic 12.1%
CAPTURE 2 Symptomatic 6.2%
EXACT Symptomatic 7.0%
*Data from CAPTURE were not analyzed specifically for age by symptomatic status.
†
Data from CAPTURE 2 and EXACT were pooled for the purposes of age-group analysis.
STUDY 30DAY: STROKE + DEATH OVERALL 30DAY: STROKE + DEATH <80 YEARS 30DAY: STROKE + DEATH ≥80 YEARS
Asymptomatic 5.4%
Asymptomatic 3.0%
Asymptomatic 3.7%
4.8% (combined)* 9.0% (combined)*
Symptomatic: 5.3%
Asymptomatic: 2.9%
†
†
Symptomatic: 10.5%
Asymptomatic: 4.4%
†
†
non-disabling stroke and had an ICA stenosis of 60% or greater in
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the index (symptomatic) carotid artery. Stenosis severity was verified by catheter angiography or duplex ultrasound and MRA. The
primary endpoint was any stroke or death within 30 days of treatment. Although the enrollment target was 872 patients, the trial was
stopped prematurely by the data safety monitoring board (DSMB)
after 527 patients had been enrolled for reasons of safety and futility. The primary endpoint was seen in 9.6% of patients in the stenting group, compared to 3.9% in those undergoing endarterectomy
(P = 0.01). Later analyses demonstrated that the difference between
the two groups persisted out to 4 years.
110
SPACE40 was a multicenter (n = 35) multinational (German,
Austrian, and Swiss participation) non-inferiority study. This trial
recruited and randomized standard–CEA risk patients within
180 days of either a TIA or moderate stroke (Rankin score <4).
Patients had a stenosis severity of 70% or greater (ECST criteria; ≥50%
NASCET) in the index carotid artery. Stenosis severity was determined by catheter angiography or duplex ultrasound. The primary
endpoint was ipsilateral stroke and death within 30 days of treatment. The trial was stopped after data from 1183 patients had been
analyzed, which led to the conclusion that a larger sample size
(almost 2500 patients) would be needed; however, further funding was not available. Event rates were 6.84% in the stenting group,
compared with 6.34% in patients undergoing endarterectomy.
Although the outcome rates were similar between the two groups,
the trial failed to demonstrate the noninferiority of CAS (i.e., the
study failed to prove that outcomes in patients undergoing stenting
were no worse than outcomes of CEA).
109
ICSS,
a multicenter (n = 50) multinational (Europe, Australia,
New Zealand, and Canada) equivalence study, recruited and randomized standard–CEA risk patients (n = 1713) to either CAS or
CEA within 12 months of symptoms. Patients had a stenosis severity of 50% or greater (by NASCET criteria) in the index carotid
artery. Stenosis severity and study entry eligibility were determined
by duplex ultrasound or other noninvasive imaging of the carotid
artery. The primary endpoint was long-term (3-year) incidence
of death or disabling stroke in any territory and has not yet been
reported. In 2010, an interim analysis reported the composite of
stroke, death, and MI at 120 days, which was 72/857 (8.5%) for the
CAS arm and 44/857 (5.2%) for the CEA arm (P = 0.006). No significant difference in the 120-day incidence of disabling stroke or
death was noted: 34/857 (4.0%) in the CAS arm vs. 27/857 (3.2%) in
the CEA group (P = NS). Following the interim analysis, the investigators concluded that pronouncement of efficacy of CAS in comparison to CEA should await the results of 3-year follow-up (2013),
and until such time, CEA should remain the treatment of choice for
symptomatic patients suitable for surgery.
Analysis and Critique
INCLUSION AND EXCLUSION CRITERIA
For the outcomes comparison between the two treatment strategies (CAS and CEA) to be valid, the two patient groups should be
comparable. Specifically, for the patients enrolled in these studies,
it should not matter whether they were in the CAS or CEA arms,
since in a well-designed, adequately enrolled randomized clinical
trial, this is not an issue. The process of randomization should cancel the noise and even out the imbalances between the two arms.
However, despite randomization, an important imbalance continued to persist between the two treated groups related to the inclusion and exclusion criteria that handicapped the outcomes in the
CAS arm. For example, in each one of these trials, patients with
known anatomical characteristics that would render them high
risk for CEA (tandem lesions, additional intracranial high-grade stenosis, “hostile necks” as a result of prior surgery or radiation) were
all excluded from trial participation. On the other hand, the trial
protocol did not specify exclusions for high stent risk. Additionally,
when the trial protocol permits trial entry and randomization on
the basis of duplex ultrasound imaging, anatomical features that
make stenting high risk (extended type III aortic arch, tortuous
extra-cranial carotid anatomy, obvious lesion filling defect[s] due
to a fresh, friable, loose thrombus) cannot be excluded. Inclusion of
these patients made little or no difference to the outcomes for CEA,
but may have negatively impacted CAS outcomes. The concept of
high–stent risk patients is a recent one, however, and the EVA-3 S
study recruited patients between the years 2000 and 2005, a time
period during which the concept of high stent risk was neither well
appreciated nor understood.
ANTIPLATELET REGIMEN
Contemporary carotid stent results are predicated on mandatory
administration of adequate doses of dual antiplatelet medications
in all patients prior to initiation of the stenting procedure and continuing them for at least 4 weeks post-CAS.
111,112
In all three of the
above trials, dual antiplatelet agent use was recommended but not
mandated. Approximately 20% of patients in the EVA-3 S and SPACE
studies did not receive adequate antiplatelet medications.
INCONSISTENT USE OF EMBOLIC PROTECTION DEVICES
In EVA-3 S, during the first 3 years of enrollment (2000-2003), EPDs
were used in approximately three quarters of the procedures. In
2003 after review of outcomes, the DSMB made use of EPDs mandatory. Analysis of the outcomes with and without use of EPDs
reveals higher complication rates in the latter group. In SPACE,
EPDs were used in only 27% of the cases. In ICSS, use of EPDs was
recommended but not mandatory. Less than three quarters of the
cases were performed using an EPD. Since the protocol was silent
with respect to the need for familiarity with these devices prior to
use within the trial, experience and expertise with the use of these
devices was minimal if any. In contemporary carotid stenting practice, careful, critical analysis of the extracranial carotid artery anatomy is an important component of the risk stratification process. If
the anatomy cephalad to the stenosis is markedly tortuous and/or
there is no adequate landing zone (i.e., there is insufficient room
between the caudal extent of the EPD and the area where the distal
tip of the stent delivery system is expected to land), unless the case
is suitable for a proximal (flow-reversal) EPD, the case should be
considered high stent risk, and carotid stenting should not be performed (rather than proceeding with unprotected carotid stenting).
OPERATOR EXPERIENCE
Among practitioners of CAS, a major concern with all three of
these studies has been the lack of experience of the investigators. Whereas the surgeons were experienced CEA operators and
needed to have performed a minimum of 25 CEA surgeries in
the year preceding study participation (EVA-3 S and SPACE), the
entry barrier for CAS operators was much lower.
113–115
In EVA-3 S,
for example, a total stenting experience of 12 CAS procedures or
5 CAS procedures plus 30 non-CAS supra-aortic stent procedures
was sufficient for entry qualification.
114
Surprisingly, first-ever CAS
cases in the presence of a proctor in the room were allowed within
the trial. A disproportionately high number of patients underwent
CAS using general anesthesia or conscious sedation, a reflection of
operator inexperience and unfamiliarity with the CAS procedure
and contrary to contemporary CAS practice. This has led many
investigators
42,116
to question the validity of establishing clinical criteria and guidelines for CAS on the basis of these trials and explain
the rationale requiring additional studies to clarify the issue.
Carotid Stenting in Symptomatic
and Asymptomatic Standard-Risk Patients
The CREST study39 conducted in 107 U.S. and 9 Canadian centers
randomized standard-risk CEA patients to either CAS or CEA. The
trial, which commenced in 2000, began by enrolling symptomatic
patients who were within 6 months from the index event. In 2005,
407
CH
32
CAROTID ARTERY STENTING
408
Prespecified Analysis Populations
enrollment criteria were modified to include asymptomatic
patients. Symptomatic patients needed to have a stenosis severity
of 50% or greater on conventional angiography (NASCET criteria),
or 70% or greater stenosis on duplex ultrasonography, CTA, or MRA
in the index carotid artery. For asymptomatic patients, the stenosis
eligibility criteria were 60% or greater on conventional angiogra-
CH
phy, 70% or greater by duplex ultrasonography, or 80% or greater
32
stenosis on CTA or MRA. Trial sponsors included the NIH as well
as a commercial partner, Abbott Vascular, whose devices (Accunet
filter and Acculink stent) were used in the study.
The primary endpoint of the CREST study was the composite of
any stroke, MI, or death from any cause during the periprocedural
period or ipsilateral stroke within 4 years after randomization. The
data were also analyzed using a composite endpoint that included
any stroke, MI, and all death within 30 days of the procedure, plus
ipsilateral stroke between day 31 and day 365. This endpoint
was used by the industry sponsor for FDA submission for device
approval. Secondary endpoints included all death, any stroke, or MI
at 30 days (periprocedural), a 1-year composite endpoint stratified
by symptomatic status and age (octogenarian status), acute procedural success, target lesion revascularization at 12 months, access
site complications requiring treatment, cranial nerve injury unresolved at 1 and 6 months, and a prespecified interaction analyses
involving gender and symptomatic status.
Data analysis was performed with four prespecified analysis
populations: (1) intent-to-treat (ITT), (2) as-treated (AT), (3) modified as-treated (MAT), and (4) per protocol (PP). These four populations are defined in
Total population 2502
ITT population 2496 (99.8%)
CAS 1259, CEA 1237
AT population 2397 (95.8%)
CAS 1151, CEA 1246
MAT population 2388 (95.4%)
CAS 1149, CEA 1239
PP population 2307 (92.2%)
CAS 1131, CEA 1176
FIGURE 3220 Prespecified analysis populations in the Carotid
Revascula ri zation Endarterectomy versus Stenting Trial (CREST). AT,
as-treated; CAS, carotid artery stenting; CEA, carotid endarterectomy; ITT, intentto-treat; MAT, modified as-treated; PP, per protocol.
Figure 32-20.
1. Primary endpoint event prior to
procedure 6
2. No procedure attempted and
withdrew consent during
study 48
3. No procedure attempted 51
4. Crossover post procedure 9
5. Pure crossover 73
6. Aborted procedure 4
7. No study stent 4
Total 82 crossovers; 70 CAS to
CEA; 12 CFA to CAS
The sample size of 2500 symptomatic patients in the initial
proposal was based on a non-inferiority analysis for a study with
80% power and one-sided alpha of 0.05, assuming a composite
endpoint rate of 7.48% and a non-inferiority margin of 2.6. When
asymptomatic patients were added in 2005, the assumption was
that 50% of the patient population would be asymptomatic. The
assumed composite rate was ratcheted down to 6.76%, and the
study power increased marginally to 82% with a one-sided alpha
of 0.05.
Of the 2307 patients in the per-protocol population, 1219 (52.8%)
were symptomatic, and 1088 (47.2%) were asymptomatic. The
demographics of the two groups were well matched; approximately 9% of the patients were octogenarians, 30% had diabetes,
and cardiovascular disease was present in about 45%.
The outcomes of the primary endpoints are shown in
Table 32-8.
Both analyses are consistent and complimentary, and CAS was
shown to be non-inferior to CEA in both analyses (pre-specified
non-inferiority margin of 2.6%).
During the peri-procedural period, there was a greater risk of
stroke with stenting (4.1% vs. 2.3%; P = 0.01), but this difference
was driven by the increased number of minor strokes in the CAS
group (3.2% vs. 1.7%; P = 0.01). It is worth noting and emphasizing that for the endpoints of death and major stroke, not only was
there no significant difference between the two groups, the event
rates for these two key endpoints was low with both CEA and CAS
(
Table 32-9).
Minor Strokes
All interventions for extracranial carotid artery disease, CEA or
CAS, are prophylactic, and the specific goal of the procedure is to
reduce the patient's future risk of a stroke. Although survival free
of a major stroke is the principal goal of the therapeutic intervention, minor strokes cannot be ignored. In fact, especially when treating asymptomatic patients, operators should have an extremely
low tolerance for any procedure-related neurological event, be it
major or minor stroke or cranial nerve injury. In the CREST study,
TABLE 32-8
CAS CEA 95% CL
Abbott PMA analysis:
1-year per-protocol
NIH analysis: 4-year ITT 7.2% 6.8% 2.26% 0.0259
*Two separate calculations were made, one by the trial sponsor Abbott and a second by the
NIH. The noninferiority margin was reached in both groups using a margin of 2.6%.
†
Prespecified noninferiority margin of 2.6%.
CAS, carotid artery stenting; CEA, carotid endarterectomy; CL, confidence limits; CREST,
Carotid Revascularization Endarterectomy versus Stenting Trial; ITT, intent-to-treat; NIH,
National Institutes of Health; PMA, premarket approval; P
Primary Endpoint Analysis from the CREST
Trial*
†
P
7.1% 6.6% 2.26% 0.0245
, noninferiority P value.
NI
NI
TABLE 32-9 Periprocedural (30 days) Primary Endpoint and Endpoint Components According to Treatment Group
Death/stroke/MI 66 (5.2 ± 0.6) 56 (4.5 ± 0.6)
Death 9 (0.7 ± 0.2) 4 (0.3 ± 0.2) 0.4 (− 0.2 to 1.0) 0.18
Any stroke 52 (4.1 ± 0.6) 29 (2.3 ± 0.4) 1.8 (0.4 to 3.2) 0.01
Major stroke 11 (0.9 ± 0.3) 8 (0.6 ± 0.2) 0.2 (− 0.5 to 0.9) 0.52
Minor stroke 41 (3.2 ± 0.5) 21 (1.7 ± 0.4) 1.6 (0.3 to 2.8) 0.01
MI 14 (1.1 ± 0.3) 28 (2.3 ± 0.4) − 1.1 (− 2.2 to − 0.1) 0.03
CAS, carotid artery stenting; CEA, carotid endarterectomy; CI, confidence interval; MI, myocardial infarction; SE, standard error.
From Brott TG, Hobson RW 2nd, Howard G, et al: Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 363:11–23, 2010.
CAS
N = 1262
NO. OF PATIENTS
% ± SE
CEA
N = 1240
NO. OF PATIENTS
% ± SE
TREATMENT EFFECT
CAS VS. CEA
PERCENTAGE 95% CI
0.7 (− 1.0 to 2.4) 0.38
UNADJUSTED
P VALUE
an increased incidence of minor strokes contributed to the excess
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stroke hazard in the CAS arm. Analysis of the NIH Stroke Scale data
of patients suffering a peri-procedural minor stroke reveals that
although residual defects were disproportionately higher in the
CAS arm at 1 month (1.10% vs. 0.60%), this difference was no longer
evident at the 6-month time point (0.6% vs. 0.6%). A similar trend to
equalization was noted when objective classification of the residual deficits was performed using the Rankin Scale. Importantly,
the occurrence of a minor stroke did not negatively impact the
patient's long-term survival. Thus, although there were more minor
strokes in the CAS arm, the neurological impairment was minimal,
and by 6 months both groups had similar outcomes.
Myocardial Infarction
In CREST, MI was defined by biomarker elevation (creatine kinase
[CK]-MB or troponin > twice the upper limit of normal) plus either
chest pain or electrocardiographic (ECG) evidence of ischemia
(>
1 mm ST elevation or depression in two contiguous leads). An
additional pre- specified category included biomarker elevation
without chest pain or ECG abnormality (biomarker positive only).
When compared to patients without biomarker elevation, mortality was higher over 4 years for those with MI (HR 3.40; 95% CI, 1.67-
6.92) or biomarker positive only (HR 3.57; 95% CI, 1.46-8.68). After
adjustment of baseline risk factors, the occurrence of MI or elevation of biomarkers only remained independently associated with
increased mortality.
117
In EVA-3-S, SPACE, and ICSS, cardiac biomark-
ers were not measured as part of the protocol.
The negative impact on survival in patients experiencing a periprocedural MI is consistent with observations from other cardiac
and non-cardiovascular procedures. It has repeatedly been shown
that small peri-procedural elevations of cardiac enzymes were
associated with increased future mortality.
118–121
How should one
interpret these findings? The occurrence of a peri-procedural MI
or biomarker elevation likely serves as a marker for more extensive underlying atherosclerotic disease. None of the other studies
referenced in this section, including CREST, was able to positively
conclude whether or not the occurrence of this procedure-related
ischemic event in some way further adds to the baseline increased
mortality risk. Thus, physicians have to factor in the occurrence as
well as the consequences of MI when making treatment recommendations for an individual patient—especially the asymptomatic octogenarian.
Cranial Nerve Injuries and Their Sequelae
Cranial nerve injuries, a consistent complication of CEA (≈5%;
Table 32-10) are rarely considered when discussing outcomes.
Some of these deficits can be permanent and on occasion can be
the source of major morbidity. For example, in the ICSS study, two
of the cranial nerve injuries (out of 857 endarterectomies) were
classified as disabling—both patients required gastrostomies. In
the CREST study, more than 80% of the cranial nerve injuries were
motor deficits, and 2% of the cranial nerve injuries were unresolved
at 6-month follow-up. In future trials, consideration should be given
TABLE 32-10
Cranial Nerve Injuries
CEA CAS
SAPPHIRE
41
EVA-3 S
109
ICSS
39
CREST
*The 1.1% rate seen in EVA-3 S was due to three events, two from patients who crossed over
to CEA (intent-to-treat [ITT] analysis).
CAS, carotid artery stenting; CEA, carotid endarterectomy.
Published Cranial Nerve Injury Rates from
Large Randomized Trials*
101
4.9% 0
7.7% 1.1%
5.3% 0.1%
5.3% 0
to the inclusion of cranial nerve injuries as part of a composite
primary endpoint together with death, stroke, and MI.
Secondary Endpoints
Pre-specified interaction analysis showed symptom status and
gender did not modify the treatment effect. However, age at treatment did have an influence, and the crossover was approximately
70 years. The impact of age on treatment selection is discussed later.
Clinical Durability of Carotid Stenting
Knowledge of the risk of an ipsilateral stroke after CAS during the
follow-up period is vital to demonstrate the clinical durability of
CAS. Clinical durability of CEA in both symptomatic and asymptomatic patients with extracranial carotid artery disease was established by NASCET
3
and ACAS.8 The rates of ipsilateral stroke during
the 4-year CREST follow-up period were low and similar in both
treatment arms—2.0% for CAS and 2.4% for CEA. These results
are similar to the rates in the EVA-3-S
110
and SPACE trials,
122
suggesting excellent durability for up to 4 years. The durable benefits
of carotid stenting (i.e., freedom from ipsilateral stroke) in these
large randomized studies reinforce the results published by the
authors almost a decade ago.
22
To further investigate the long-term
outcomes following carotid intervention, subject follow-up in the
CREST study has been extended to 10 years and will provide additional information on this issue.
Restenosis Following Carotid Stenting
Restenosis rates have been documented following CAS in the large
randomized trials and are approximately 10% at 2 years,
sured by duplex ultrasonography. Although duplex ultrasound is an
excellent method of following these patients, velocity criteria conventionally applied to diagnose stenosis in nonstented arteries may
require modification because of mechanical changes in the carotid
artery following stenting. It has been suggested that a peak systolic
velocity greater than 300 cm/s be used to define a stenosis of 70%
in the stented patient. Other modalities also present challenges.
Computed tomography angiography may be used as a complementary form of imaging,
127
but it requires contrast and radiation exposure.
Magnetic resonance angiography is not useful in a stented patient.
Evaluating restenosis by tracking the need for target lesion
revascularization is a commonly accepted method to define
clinically relevant in-stent restenosis. At 1-year follow-up, both
CAS and CEA had close to 99% freedom from target lesion
revascularization,
39
with only 0.8% of patients requiring repeat
revascularization. Furthermore, even in patients with evidence
of in-stent restenosis, the event rate is low, suggesting restenosis
is generally a benign condition.
123
These results, together with
previously reported very low rates of carotid stent restenosis,
support durability of the self-expanding stent for this indication. Since the stent is implanted within a superficial artery that
is subject to a variety of torsional forces associated with neck
movement, questions of stent fracture have been raised and are
being addressed by follow-up fluoroscopy in some ongoing tri-
128
als.
In the authors’ experience, stent thrombosis, stent fractures,
and in-stent restenosis are rare issues for stents placed in the
extracranial cervical carotid location. The rate of stent fracture is
currently under study.
122,123
as mea-
124–126
Summary of CREST Results
1. In experienced hands, both CEA and CAS are excellent revas-
cularization options for treatment of symptomatic and asymptomatic extracranial carotid stenosis in patients of either
gender.
2. Both procedures were associated with similar rates of the pri-
mary composite outcome that included periprocedural stroke,
MI, or death and subsequent ipsilateral stroke to 4 years.
409
CH
32
CAROTID ARTERY STENTING
410
3. Not only was there no significant difference between major
disabling stroke and death between the CAS and CEA arms,
the incidence of these major events was very low with either
treatment option.
4. Minor non disabling strokes were greater with CAS than with CEA.
CH
Using the objective NIH Stroke Scale, at 6 months, the deficits in
the stenting cohort had equalized with those in the CEA arm of
32
the study. The occurrence of a minor stroke did not affect survival.
5. Myocardial infarction's were more frequently seen with CEA
than CAS, and the occurrence of MI negatively impacted survival.
6. Cranial injuries were seen in approximately 5% of the CEA
patients, the vast majority were motor deficits, and 2% of the injuries had persistent deficits at 6 months. There were no cranial
injuries in the CAS patients.
7. At one year, stroke had a greater adverse effect than MI on a
broad range of health status domains.
129
Special Patient Groups
Carotid Stenosis Following Cervical Irradiation
Carotid artery stenosis is a delayed complication of neck irradiation (radiation arteritis).
tion is often seen at the carotid bifurcation, patients with prior neck
radiation frequently have lesions that are high (at or above the C2
vertebra) or low (at or below the level of the clavicle). Stenosis at
multiple locations within the same artery is not unusual. The typical interval between the radiation treatment and detection of stenosis is at least 10 years. In patients who had neck irradiation but
also have multiple risk factors for atherosclerotic vascular disease
and who present with an isolated bifurcation stenosis, it may be
very difficult to determine the etiology of the carotid disease.
Surgical treatment of these patients is complicated by a number of factors. Many patients have had radical neck dissections in
association with radiation therapy, resulting in fibrosis and scarring.
There is an increased risk of stenosis of the CCA, its low position
making surgical access more difficult. There is also an increase in
postoperative necrosis, infections, wound breakdown, and cranial
nerve palsies that have been observed post CEA in this popula-
131
tion,
compared to patients without prior radiation. In contrast,
none of these difficulties are faced by operators performing CAS,
making it an appealing technique for this indication.
Owing to the infrequent nature of this presentation, there are
no randomized studies; however, several case series have demonstrated that CAS is safe and efficacious in this setting.
peri- procedural stroke and death rates have been low and have not
exceeded those observed in general patient cohorts undergoing CAS.
The only limitation of stenting in this group is the possible increased
risk of in-stent restenosis following the procedure. Restenosis rates
from 5%
132
to 41%
24 months. Although higher than that seen in patients without prior
radiation, these events have not been associated with symptoms and
restenotic lesions are amenable to repeat percutaneous intervention.
Despite the absence of randomized trial data apart from those
patients enrolled in the SAPPHIRE study, the low peri-procedural
complication rates with CAS makes this the preferred approach for
this patient group and the authors support the level IIa recommendation of the multispecialty guidelines
of CAS for carotid stenosis following cervical radiotherapy. Patients
should be closely followed by serial duplex ultrasound examinations after the procedure to monitor for restenosis. Because of problems of delayed healing and incomplete endothelialization of the
stent struts, patients with prior neck radiation who undergo stenting
are prescribed lifelong dual antiplatelet treatment.
Post–Carotid Endarterectomy Restenosis
Restenosis after CEA is a well-recognized phenomenon.
Restenosis that occurs within the first 2 years after CEA has been
attributed to intimal hyperplasia, whereas after 2 years, progressive
130
Although stenosis following prior radia-
132,133
133
have been reported at intervals from 12 to
32
in recommending the use
Reported
atherosclerosis is thought to be responsible. Restenosis rates vary
depending on the study and methodology and are reported from
5% at 1 year
123
to 36% during long-term follow-up.
134
Revision CEA
is technically challenging and associated with higher complication rates than primary surgery, with increased rates of stroke
(4.8% vs. 0.8%), TIA (4.0% vs. 1.1%), and cranial nerve injury (17.0%
vs. 5.3%).
135
Carotid artery stenting is therefore an appealing tech-
nique in this setting.
There have been no randomized trials to assess which method
is superior. Single-center studies evaluating the experience of
CAS following prior CEA have demonstrated that low complication rates can be achieved. Thirty-day death/stroke rates ranging from 1%
favorably to endarterectomy.
are slightly superior to those seen in randomized trials of symptomatic patients.
136
137
to 4%
have been published and have compared
136
Of note, these published figures
39
The durability of CAS after previous CEA has
not been well established; however, the limited data suggest
that stent restenosis is not significantly higher than that seen in
primary CAS.
137
Given that the current literature demonstrates no particular
increase in CAS risk following prior CEA but a significant increase
in complications during revision CEA, CAS is the recommended
approach in this setting.
Carotid Stenting in Women
Some authors have postulated a variance in outcomes
dependent on the sex of the patient. Women typically have
smaller- caliber arteries and aortic arches, potentially leading to increased technical difficulties and higher complication rates. Although individual trials have not had sufficient
power to detect such differences, the Carotid Stenting Trialists
Collaboration (CSTC) published a meta-analysis of three randomized controlled trials. This study revealed no significant
difference in outcomes at 4 years between men and women,
although there was a trend toward higher adverse event rates
138
in men.
women are more likely to have complications following CAS,
and men more likely after CEA.
A separate review of the CREST study data found that
139
The authors suggested that
the treatment strategy for carotid stenoses could be customized, with a preference for CEA in women and vice versa. If
the data from this study are further pooled with the data from
CSTC, there is no significant difference in outcomes.
140
Given
the conflicting study data and absence of clear evidence, there
is currently no basis for tailoring treatment approaches on the
basis of gender.
Carotid Stenting in the Elderly
Elderly patients (generally interpreted to mean patients > 80 years)
with carotid stenosis pose several challenges for carotid revascularization. The association between older age and increased risk of
adverse events after CAS was seen in the CREST lead-in cohort,
the SPACE trial,
40
and the ICSS.
109
Indeed, octogenarian patients are
more likely to be excluded because they have one or more features deemed high risk for carotid stenting, as shown in
By carefully excluding patients with adverse features—decreased
cerebral reserve, excessive tortuosity (2 bends >90 degrees after
the origin of the CCA from the aortic arch or ICA from the carotid
bifurcation), or heavy concentric calcification—it has been shown
that adverse event rates comparable to those seen following CEA
can be achieved.
In the CREST study, an interaction between age and treatment
efficacy was detected with a crossover at an age of approximately
70 years. This led the CREST investigators to conclude that “carotidartery stenting tended to show greater efficacy at younger ages,
and CEA at older ages.”
39
Hence, treatment recommendation in the
elderly patient with carotid stenosis must be highly individualized
and take into account high-risk features that will make stenting or
CEA (or both options) unsuitable.
141
Box 32-1.
142
Treatment of Carotid Stent Restenosis
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On the rare occasion when treatment is deemed necessary, treatment of in-stent restenosis is usually performed by dilation with
either a noncompliant or cutting balloon.
143
In some cases, vessel
recoil makes an additional stent necessary. It has been speculated
that the controlled trauma of a cutting balloon may result in lower
occurrence of in-stent restenosis than a conventional angioplasty
balloon, but this has not been studied systematically. Zhou et al.
used cutting balloons in five of seven patients, and two required
further stent implantation.
144
In theory, because restenotic lesions
are generally fibrotic, the risk of periprocedural embolization in
these lesions (in-stent restenosis or stenosis recurrence following
endarterectomy) is thought to be low. However, in practice, use of
a distal EPD is recommended even when intervening on these
lesions. Rates of target lesion revascularization in the CREST study
were very low, with only 0.8% of patients requiring repeat intervention during the 4-year follow-up period.
1.5% was obtained from the 4-year published data from EVA-3 S.
39
A comparable rate of
110
Treatment of Concomitant Carotid
and Coronary Arterial Disease
The generalized nature of atherosclerosis makes concomitant
coronary and carotid artery disease a common finding. The issue
of treatment of carotid disease is of particular concern in the
management of patients who require CABG. These patients have
a high incidence of at least moderate carotid artery disease (15%
of patients >
70 years of age
ciated with a 25% mortality.
studies have found that stroke as a complication of CABG occurs
in 1.7% of all cases.
asymptomatic 50% to 99% unilateral stenosis, 5% for those with
bilateral 50% to 99% stenoses, and 7% to 11% for patients with a
carotid artery occlusion.
cal examination revealed that only 40% of such strokes could be
attributed to the ipsilateral stenosis. Therefore, even if 100% effective at preventing ipsilateral ischemia, carotid intervention can
only reduce peri-operative (CABG) stroke rates by less than half.
This issue is further clouded because there are currently no randomized trial data to provide guidance as to the optimal management of these patients.
Observational studies have evaluated the outcomes of both CEA
and CAS, either prior to or concurrently with CABG. A meta-analysis of
published peri-operative stroke/death rates for combined CEA/CABG
revealed a stroke/death rate of 8.7% for combined surgery and 6.1%
for a staged CEA then CABG.
for a staged procedure comes at the cost of an increased MI rate, from
3.6% for the synchronous procedure to 6.5% for staged.
significant concern because peri-procedural MI has been associated
with an increased risk of mortality, as seen in the CREST study.
SAPPHIRE study, which enrolled high-risk surgical patients (including
those requiring CABG), showed that in high -risk patients, CAS was a
safer alternative than CEA, with lower combined death and stroke
rates at 1 year.
101
This finding has been further supported by a retrospective study comparing outcomes between CEA and CAS followed
by CABG. Again there was both a numerical reduction in 30-day
death/stroke rates (7.1% vs. 12.6%, respectively; P = 0.28) and MI (3.3
vs. 12.6%, respectively; P = 0.06). This has led to staged CAS followed
by CABG at least 14 days later following cessation of at least one antiplatelet agent being adopted by many centers.
ies have reported periprocedural death/stroke rates of 4.8%.
At present there are no randomized data to support either
approach in asymptomatic patients. Patients with three-vessel CAD
were not enrolled in the landmark studies for asymptomatic carotid
8,151
disease
; the study findings may not necessarily be extrapolated to this high-risk population. Overall, the authors believe that
patients with bilateral carotid artery disease or unilateral carotid
stenosis plus a contralateral occlusion are most likely to benefit
145
) and perioperative stroke is asso-
146
Large meta-analyses of published
146,147
This risk is to 3% for patients with an
146
However, pathological and radiologi-
148
However, this reduction in stroke risk
148
149
Single-center stud-
This is a
117
The
150
from carotid revascularization prior to CABG, and that CAS is a
safer alternative to CEA where feasible.
Current Recommendations
and the Future of Carotid Artery Stenting
Stroke is the fourth leading cause of death in the United States
and the single most important cause of long-term physical and
intellectual disability. Despite spectacular advances and progress in
several areas of medicine, the treatment options for an established
stroke are limited, and the expectation for reversibility or improvement of a neurological deficit is both guarded and unpredictable.
Given the high risk of recurrence after a symptomatic event,
there is little controversy or argument that most if not all symptomatic patients with 70% or greater stenosis on angiography, and
many symptomatic patients with a 50% to 70% stenosis, should be
offered a definitive revascularization procedure—either CEA or
CAS—unless the expected procedural risks breach the AHA recommendation threshold of 6%. Additionally, these patients should
be on appropriate atherothrombotic risk-reduction measures.
For asymptomatic patients, however, the issue of which patient
needs treatment is far from settled. It would be reasonable to offer
revascularization for asymptomatic patients with 80% or greater
stenosis. In certain situations (e.g., those requiring CABG), patients
with less than 80% but more than 70% stenosis also may be offered
treatment. Carotid stenting can be scientifically and ethically
justified as a treatment option for asymptomatic patients only if
operators and centers are experienced and have a verifiable periprocedural risk of 3% or less. If the expected peri- procedural risk
associated with revascularization (CEA or CAS) in an asymptomatic
patient exceeds 3%, the patient should be managed conservatively.
Patient selection remains the single most important predictor
of complications. Although EPDs are routinely used, no protection device can replace critical risk analysis and sound operator
judgment. In general, it is reasonable to recommend CAS in symptomatic patients who are younger than 80 years of age. For patients
older than 80, the decision must be individualized, and the recommendation for revascularization should be arrived at after a rigorous and critical analysis of the risks and benefits. Many of these
patients may be best managed medically—no CAS or CEA.
For asymptomatic patients considered high risk for endarterectomy, CAS is a reasonable option with two important caveats: (1)
high risk for endarterectomy does not automatically mean high
risk for stroke (with conservative medical management), and (2)
a proportion of high surgical risk patients will also be high risk for
CAS—these patients should be treated conservatively.
The conventional approach for treatment of extracranial carotid
artery disease involves revascularization on the basis of the presumed surgical risk (the conventional paradigm depicted in
Fig. 32-21). In other words, if a patient requires treatment for carotid
stenosis, the first question that has been traditionally posed is: Is
the patient standard risk for CEA? Patients considered high risk for
Carotid
revascularization
Ye s
Evaluate CEA risk
Standard
CEA
or
Eligible for participation
in randomized trial
FIGURE 3221 Conventional approach to treatment of carotid arterial
disease has been based on the answer to the question: Is the patient suitable
(standard risk) for carotid endarterectomy (CEA)? CAS, carotid artery stenting.
No
Medical therapy
High
CAS
152
411
CH
32
CAROTID ARTERY STENTING
412
Carotid
revascularization
CH
32
Ye s
Evaluate CAS risk*
Standard
CAS
No
Medical therapy
High
Evaluate CEA risk
or
Eligible for participation
in randomized trial
Standard High
CEAConsider medical
therapy
*Age, Cerebral reserve, Lesion, and Vessel morphology
FIGURE 3222 In the future, we will see a paradigm shift, and the
approach to carotid revascularization will be based on the answer to
the question: Is the patient suitable (standard risk) for carotid artery
stenting (CAS)? CEA, carotid endarterectomy.
CEA are often referred for carotid stenting, arbitrarily considered
a low-risk intervention because little attention had been paid to
defining what constituted high stent risk. However, the full clinical
potential of carotid stenting can only be realized if there is a paradigm shift in the process of procedural risk stratification and selection of patients for revascularization. This applies to both everyday
clinical practice and the design of randomized trials. Clinical decision making that incorporates this paradigm shift is depicted in the
future approach shown in
Figure 32-22, wherein the first question
that should be asked is: Is the patient standard risk for stenting?
So, what can we expect in the future? A randomized trial to
answer the question of the risk of stroke with contemporary medical treatment in asymptomatic patients is already underway
(SPACE II), and another trial (CREST II) is awaiting funding. ACT I,
a large prospective study involving asymptomatic patients is randomizing patients (3:1, CAS vs. CEA). Although this study does not
include a medical arm, prior to randomization, patients have to be
suitable (i.e., standard risk) for both CAS and CEA—an important
strength of the trial design. Finally, in the future we can expect continued technical and device improvements to further improve the
safety of carotid stenting.
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