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Overview of carotid artery stent placement for carotid stenosis

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        NATIONAL INSTITUTE FOR CLINICAL
                  EXCELLENCE
             INTERVENTIONAL PROCEDURES PROGRAMME

    Interventional procedures overview of carotid artery
            stent placement for carotid stenosis
Introduction
This overview has been prepared to assist members of the Interventional Procedures
Advisory Committee (IPAC) advise on the safety and efficacy of an interventional
procedure previously reviewed by SERNIP. It is based on a rapid survey of published
literature, review of the procedure by Specialist Advisors and review of the content of
the SERNIP file. It should not be regarded as a definitive assessment of the
procedure.

Procedure name
•    Carotid artery stent placement for carotid stenosis.

Specialty societies
Specialist advice was sought from
• Vascular Surgical Society of Great Britain and Ireland.
• British Cardiac Society.
• British Cardiovascular Interventional Society.
• Society of British Neurological Surgeons.
• British Society of Neuro-Radiologists.
• British Society of Interventional Radiology.
• Royal College of Radiologists.
• Association of British Neurologists.

Description
Indications
Stroke is a leading cause of morbidity and mortality in the UK. Stroke secondary to
carotid stenosis occurs when a major portion of one or both carotid arteries (the
arteries in the neck that supply blood to the brain) is narrowed or blocked. Carotid
stenosis increases the risk of ischemic stroke by acting as an embolic source.

People with asymptomatic carotid stenosis have a lower risk of stroke than those with
symptomatic disease. The risk of recurrent stroke in recently symptomatic patients with
severe carotid stenosis is as high as 28% over 2 years. 1


Current treatment and alternatives
Treatment for carotid stenosis involves reducing the progression of plaque growth and
the risk of thromboembolism through medical therapies and risk-factor modification. In
addition plaques may be removed by surgery (carotid endarterectomy (CEA), or
treated by angioplasty and stenting.




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Carotid endarterectomy has been the standard treatment for patients with symptomatic
stenosis. It may be indicated to prevent new strokes from occurring where carotid
stensosis is greater than 70%. The procedure involves making an incision in the neck
under local or general anaesthesia. The carotid artery is then opened and the plaque
removed. Although trials have demonstrated that surgery significantly reduces the risk
of stroke in patients with severe symptomatic carotid stenosis there is still a risk of
stroke or death resulting from surgery.2 Surgery can also be complicated by wound
haematoma and cranial nerve damage. Many patients with carotid artery stenosis also
have ischaemic heart disease and surgery can thereby be associated with increased
risk of myocardial infarction.


Carotid stenting is a less invasive percutaneous procedure than carotid
endarterectomy for the treatment of carotid stenosis. This procedure has evolved from
percutaneous transluminal angioplasty (PTA) and avoids the need for an incision in the
neck. However it also carries a risk of stroke both during and immediately after the
procedure.

Summary of procedure
Carotid stenting is carried out under local anaesthetic. The procedure involves passing
a fine wire into the carotid artery through the femoral artery in the groin. A small
balloon catheter may be passed over this to pre-dilate the narrowed artery before
inserting a metal mesh (stent) which keeps the artery open to maintain blood flow and
to prevent restenosis.

A cerebral protection device may also be used in this procedure. These devices are
designed to prevent particles dislodged during the stenting procedure from passing
into the cerebral circulation .Once the stent has been implanted, the protection device
is removed through the delivery catheter.

Summary of the evidence
Efficacy

Evidence from the Cochrane review comparing endovascular treatment for carotid
artery stenosis with carotid endarterectomy suggests that the two procedures have
similar early risk of death or stroke and similar long-term benefits. A meta-analysis of
five randomised controlled trials found no significant difference between the odds of
death or any stroke at 30 days post procedure (odds ratio 1.26; 95% confidence
interval [CI] 0.82–1.94) and at 1 year following the procedure (odds ratio 1.36; 95%
[CI] 0.87–2.13).

The rate of stroke or death within 30 days reported in the non-randomised studies
series ranged from 5.3% (357/6753) to 10% (15/150) without cerebral protection and
from 1.8% (16/896) to 5.2% (5/97) with cerebral protection.

Substantial heterogeneity exists within the studies on this procedure, making it difficult
to interpret the evidence. This particularly relates to the evolving nature of the
procedure and the differing characteristics of patients (asymptomatic versus
symptomatic) included in the studies.

Restenosis and recurrent stroke rates were not reported in the majority of studies.

The Specialist Advisors expressed uncertainty around the efficacy of this procedure in
comparison with surgery. They considered that the long-term results were still



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unknown and it was still unclear which patients were most likely to benefit from the
procedure.

Safety
Data from a carotid artery stent registry indicates that mortality related to the
procedure ranged from 0.33% (7/2110) for asymptomatic patients treated with cerebral
protection to 1% (43/4282) for symptomatic patients treated without protection.

The Cochrane review suggests that endovascular treatment (including the use of
stents) significantly reduces the risk of cranial neuropathy in comparison with carotid
endarterectomy (odds ratio 0.12; 95% [CI] 0.06–0.25). In one of the randomised trials
included in the review there were no cases of cranial neuropathy in patients
undergoing carotid stenting, but 12 patients (22.6%) experienced hypertension
requiring treatment; seven (13.2%) experienced transient bradycardia; three (5.7%)
had haematomas and one (1.9%) had an arterial thrombosis.

The Specialist Advisors expressed uncertainty about the safety of the procedure in
comparison with surgery. They listed potential complications as procedure-related
stroke or death, groin haematoma, thrombosis, rupture and perforation.

Literature review
The medical literature was searched to identify studies and reviews relevant to carotid
artery stent placement for carotid stenosis. Searches were conducted using the
following databases: MEDLINE, PREMEDLINE, EMBASE, Cochrane Library and
Science Citation Index, and covered the period from their commencement to June
2004. Trial registries and the Internet were also searched. No language restriction was
applied to the searches.

The following selection criteria were applied to the abstracts identified by the literature
search. Where these criteria could not be determined from the abstracts the full paper
was retrieved.


Appraisal criteria

 Characteristic      Criteria
 Publication type    Clinical studies included. Emphasis was placed on identifying good quality published studies.
                     Abstracts were excluded where no clinical outcomes were reported, or where the paper was
                     a review, editorial, laboratory or animal study.
                     Conference abstracts were also excluded because of the difficulty of appraising
                     methodology.
 Patient             Patients with carotid stenosis.
 Intervention/test   Carotid artery stent placement with or without cerebral protection devices.
 Outcome             Articles were retrieved if the abstract contained information relevant to the safety and/or
                     efficacy.
 Language            Non-English-language articles were excluded unless they were thought to add substantively
                     to the English-language evidence base.




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Studies included in the overview
This overview is based on seven studies, including two systematic reviews 2, 3.

One of the reviews (Cochrane review) assesses randomised controlled trial evidence
comparing endovascular with surgical treatment for carotid stenosis,2 the second
review looks specifically at the issue of cerebral protection devices in carotid stenting 3
and is based predominately on case-series evidence.

Two randomised controlled trials are also included in the data extraction table, one of
these trials is included in the Cochrane systematic review 4; the other is a more recent
trial by the same study group looking at a different population 5.

The other studies included in this review are non-randomised or case-series studies.
These were chosen because they reflected the evolving nature of the procedure and
the associated risks and benefits.

Appendix A includes a list of studies not included in the data extraction tables, but
relevant to the review of this procedure.

Existing reviews on the procedure

A Cochrane review on percutaneous transluminal angioplasty and stenting for carotid
artery stenosis was identified 2.This review includes studies looking at angioplasty with
or without the use of stents.




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   Table 1 Summary of key efficacy and safety findings on carotid artery stent placement

Abbreviations used: CAS – coronary artery stenting; CEA – carotid endarterectomy; OR – odds ratio; CI – 95% confidence interval; TIA – trans ischaemic attack
Study details                   Key efficacy findings                                                Key safety findings                    Comments
Coward et al (2004) 2           Outcomes reported: periprocedure stroke or death within 30 days      Complications:                         Cochrane review
                                of procedure; subsequent ipsilateral carotid territory stroke;       Cranial neuropathy within 30 days
Literature search: June         subsequent stroke in any arterial territory; periprocedure cranial   of procedure (results from 4 studies) Good quality systematic review
2003/September 2003             neuropathy; restenosis; other complications                                                                 – limited to randomised
Systematic review.                                                                                   There was a significant difference in controlled trials. Background
                                Death or any stroke within 30 days of procedure                      the rate of cranial neuropathy in      section does discuss results
Patients with symptomatic or    (results from 5 studies)                                             patients treated endovascularly        from non-randomised
asymptomatic carotid artery     There was no significant excess of death or strokes in either group. compared with those treated            controlled trials
stenosis.                       OR (endovascular: surgery) 1:26; 95% CI 0.82–1.94. There was         surgically. OR
                                significant heterogeneity between trials                             (endovascular:surgery) 0:22; 95%       Review intended to determine
Selection criteria:                                                                                  CI 0.06–0.25. There was no             subsequent stoke rate in
Randomised controlled trials of Death or disabling stroke within 30 days of procedure                heterogeneity between trials           patients – however this data
carotid endovascular treatment (results from 3 studies)                                                                                     was not available
compared with carotid           There was no excess of death or disabling stroke in either group.
endarterectomy, or              OR (endovascular: surgery) 1:22; 95% CI 0.61–2.41. There was no                                             Authors note that centres that
endovascular treatment plus     significant heterogeneity between trials                                                                    took part in the trials had a
best medical therapy                                                                                                                        specific interest in secondary
compared with best medical      Death or any stroke within one year following procedure                                                     prevention – may be an issue
therapy alone.                  (results from 2 studies)                                                                                    with generalisabiity
                                There was no significant difference in the odds of death or any
Studies included:               stroke at one year following endovascular treatment with surgical                                           Endovascular techniques were
CAVATAS 2001 6 (angioplasty     treatment. OR (endovascular: surgery) 1:36; 95% CI 0.87–2.13.                                               not the same for all the trials –
with or without stenting)       There was borderline heterogeneity between trials                                                           different devices and use with
Kentucky 2001 4                                                                                                                             and without cerebral protection
                                Death or stroke or myocardial infarction within 30 days of
Leicester 1998 7                procedure (results from 5 studies)                                                                          Two of the studies were
Wallstent 2001 8, 9 –           There was no difference. OR (endovascular: surgery) 0.99; 95% CI                                            stopped early because of
(unpublished data).             0.66–1.48. There was significant heterogeneity between trials                                               concerns over stenting 7-9

SAPPHIRE 2002 –                        Restenosis rates were only available for one study 6. Results                                          Unpublished data was also
(unpublished data – trial halted       suggesting that one year after treatment, ipsilateral carotid stenosis                                 presented and included for two
due to low enrolment).                 of 70–99% was more common after endovascular treatment.                                                of the trials




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Abbreviation used: CAS – coronary artery stenting; CEA – carotid endarterectomy; OR – odds ratio; CI – 95% confidence interval; TIA – trans ischaemic attack
Study details                   Key efficacy findings                                                  Key safety findings                    Comments
Brooks et al (2001) 4           Outcomes reported: complications, length of hospital stay,             Complications:                         This study is included in the
                                patient’s perception of pain                                           Stenting group                         Cochrane systematic review
                                                                                                                                              2
Randomised controlled trial                                        Stenting        Surgery                1 patient (1.9%) had a arterial
                                Death/cerebral ischemia                                                   thrombosis                          Method of randomisation not
104 patients                    Death                              0               1                      3 patients (5.7%) had               stated.
                                Stroke                             0               0                      haematomas requiring treatment Cerebral protection devices
51 patients underwent carotid   Transient cerebral ischemia        1               0                      7 patients (13.2%) experienced      were not used
stenting without protection     Length of stay                     5.2 days        3.7 days               transient bradycardia (received
Mean age: 69.6 years            Perception of pain (0–10)          1.2             2.7                    temporary pacing)                   Limited reporting of efficacy
                                                                                                          12 patients (22.6%) experienced     outcomes. Unclear when
53 patients underwent carotid   Patency: Authors reported that patency of treated arteries remained       hypertension requiring treatment    outcomes measured
endarterectomy                  acceptable after 2 years in both groups and the average post                                                  Boston scientific provided
Mean age: 66.4 years            angioplasty and stenting stenosis decreased from a mean baseline       Surgery group                          devices for endovascular
                                stenosis of 82.4 to a mean of 5.0                                         1 patient (2%) had a                group
Inclusion criteria: those                                                                                 haematomas requiring treatment
sustaining events confined to                                                                             4 patients (7.8%) had               Authors note that the study is
the carotid circulation within                                                                            cranial/cervical nerve injury       limited by being single centre
three months; > 70% stenosis                                                                              3 patients (5.9%) experienced       with a select team experienced
                                                                                                          hypertension requiring treatment    in the management of
Follow-up: 24 months                                                                                                                          cerebrovascular disease and
                                                                                                                                              performing endovascular
                                                                                                                                              procedures
Brooks et al (2004) 5                 Outcomes reported: complications, length of hospital stay,         Complications:                      Method of randomisation not
                                      patient’s perception of pain                                       Stenting group                      stated
Randomised controlled trial                                                                                 5 patients (11.3%) experienced
85 patients                                                   Stenting        Surgery                       transient bradycardia            Cerebral protection devices
44 patients underwent carotid         Stroke/TAI              0               0                                                              were not used
stenting without protection           Length of stay          1.5. days       1.7 days                   Surgery group
Mean age: 66.6 years                  Perception of pain      1.1             2.0                           3 patients (7.1%) had            Authors note that the study is
                                      ([0–10] 24 hours)                                                     cranial/cervical nerve injury    limited by being single centre
42 patients underwent carotid                                                                               4 patients (9.5%) experienced    with a select team
endarterectomy                        Authors note that the average post procedural stenosis for            nausea, vomiting due to          experienced in the
Mean age: 69.9 years                  stenting decreased to 5.0                                             anaesthesia.                     management of
Inclusion criteria:                                                                                                                          cerebrovascular disease and
asymptomatic patients                                                                                                                        performing endovascular
                                                                                                                                             procedures.
Follow-up: 48 months




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Abbreviation used: CAS – coronary artery stenting; CEA – carotid endarterectomy; OR – odds ratio; CI – 95% confidence interval; TIA – trans ischaemic attack
Study details                    Key efficacy findings                                                 Key safety findings                    Comments
CARESS (2003) 10                 Outcomes reported: death and or stroke from any cause within 30       Complications:                         Authors describe this as a
                                 days of the procedure (primary); any cause death and or stroke and    See efficacy section – other           phase I trial (equivalence trial)
Non randomised comparative       documented myocardial infarction (MI) within 30 days (secondary)      complications not reported.#           – power and sample size were
study                                                                                                                                         determined by event rates in
                                 Primary endpoint: Death and or stroke from any cause within 30                                               the CEA arm
Multicentre (14 sites USA)       days of the procedure
                                                                                                                                              Target was 450 subjects (300
April 2001–December 2002                                    CAS              CEA                                                              CEA and 150 CAS)
                                 Number at risk             143              254
Patients with symptomatic (≥     Number of events           3 (2.1%)         6 (2.4%)                                                         Investigators had to have
50%) and asymptomatic            Number censored            9                35                                                               experience with both
(≥ 75%) carotid stenosis         K-M estimate               0.0216           0.0239                                                           procedures
                                 p = 0.8502
Patients with stenting had                                                                                                                    Forty-two patients (33 CEA
embolic protection               CAS events occurred on the day of the procedure and on                                                       and 9 CSS) withdrew from the
                                 postprocedural days 13 and 14.                                                                               study prior to treatment
143 patients undergoing CAS                                                                                                                   (reasons given for all
254 patients undergoing CEA      CEA events occurred on the day of the procedure (n = 3), two on                                              withdrawals)
                                 the first postoperative day (n = 2) and another 7 days post
Baseline characteristics did not procedure.                                                                                                   Surgeons carried out CEA and
differ between the two groups                                                                                                                 vascular surgeons;
                                 Secondary endpoint: Any cause death and or stroke and                                                        interventional radiologists and
                                 documented myocardial infarction (MI) within 30 days                                                         neurologists carried out CAS
Follow-up: 30 days
                                                            CAS              CEA
                                 Number at risk             143              254
                                 Number of events           3 (2.1%)         8 (3.1%)
                                 Number censored            9                35
                                 K-M estimate               0.0299           0.0412
                                 p = 0.5998

                                       At 30 days, 91% of treated patients completed the 30-day follow-up
                                       visit.




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Abbreviation used: CAS – coronary artery stenting; CEA – carotid endarterectomy; OR – odds ratio; CI – 95% confidence interval; TIA – trans ischaemic attack
Study details                   Key efficacy findings                                                  Key safety findings                    Comments
Kastrup et al (2003) 3          Outcomes reported: occurrence of minor and major strokes and           Complications:                         PubMed, reference lists and
                                death within 30 days.                                                  This was not the aim of the paper      hand searching
Systematic review                                                  Events per procedure                (see efficacy section)
                                                          Without protection        With protection                                           0.8% of all patients without
Literature search: January                                                                                                                    protection had actually
1990 – June 2002                Minor stroke              94/2537 (3.7%)            5/869 (0.6%)                                              undergone cerebral protection
                                Major stroke              28/2537 (1.1%)            3/869 (0.3%)                                              (testing of devices)
26 studies looked at CAS        Death                     18/2537 (0.7%)            8/896 (0.9%)
without cerebral protection     Any stroke or death       140/2537 (5.5%)           16/896 (1.8%)                                             Authors note that in most
(n = 2357)                                                                                                                                    studies the results for patients
59% symptomatic patients        The combined stroke or death rate was significantly different                                                 with symptomatic or
41% asymptomatic patients       between the two groups (p < 0.001). This was mainly due to a                                                  asymptomatic coronary artery
Mean age: 69 years              decrease in minor strokes (p < 0.001) and major strokes (p < 0.05)                                            disease were not presented
                                                                                                                                              separately
11 studies looked at CAS with   Authors note that there was a 3-fold increased risk of any stroke or
cerebral protection (n = 839)   death and a greater than 6-fold increase in minor stroke within 30                                            Patients were on antiplatelet
64% symptomatic patients        days of CAS without protection compared with protection                                                       therapy following the
36% asymptomatic patients                                                                                                                     procedure
Mean age: 68 years
                                                                                                                                              Unclear whether quality criteria
To be included, studies had to                                                                                                                were used to assess studies
include at least 10 stent
procedures                                                                                                                                    Review does include a variety
                                                                                                                                              of study designs. Authors note
Articles were excluded if only                                                                                                                that caution should be taken
angioplasty without stent                                                                                                                     when interpreting the results
placement had been                                                                                                                            because of the heterogeneity.
performed

No significant differences
reported between the groups




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Abbreviation used: CAS – coronary artery stenting; CEA – carotid endarterectomy; OR – odds ratio; CI – 95% confidence interval; TIA – trans ischaemic attack
Study details                   Key efficacy findings                                                  Key safety findings                    Comments
Wholey et al (2003) 11          Outcomes reported: complications incurred during procedure and         Complications:                         Authors note that only 39/53
                                within the 30-day period                                               Procedure-related deaths for           centres actively participated in
Registry/survey – Global                                                                               asymptomatic and symptomatic           all the questions
carotid artery stent registry   12254/12392 (98.9%) of arteries were considered to have been a         patients and patients with or without
                                technical success                                                      cerebral protection                    Data is primarily observational
53 participating centres        The combined stroke and procedure-related death was 3.98%.                                                    and retrospective
Europe, South and North         Based on the total vessels treated, there were                         Procedure-related deaths for:
America and Asia                • 265 (2.14%) minor strokes                                            All symptomatic patients 0.85%         Reporting of complications
                                • 149 (1.20%) major strokes                                            • Symptomatic patients without         varied amolng the centres
September 2002 most recent      • 79 (0.64%) deaths related to the procedure                              protection 1%
update                                                                                                 • Symptomatic patients with            Evidence of a learning curve
                                There were 95 (0.77%) non-procedure-related deaths within the 30-         protection: 0.52%                   associated with this procedure
11,243 patients with 12,392     day period, resulting in a total stroke and death rate of 4.75%.       All asymptomatic patients 0.42%
diseased carotid arteries       Based on the total number of patients, the total stroke and death      • Asymptomatic patients without        Authors note that since the
                                rate was 5.23%                                                            protection 0.49%                    original study in 1997 the rate
                                                                                                       • Asymptomatic patients with           of stroke and procedure-
                                Immediate and within 30 day complications (asymptomatic vs.               protection (0.33%)                  related death has fallen from
                                symptomatic)                                                                                                  5.7% to 3.98%

                                      There was a 4.94% rate of stroke and procedure related deaths in
                                      the symptomatic group and 2.95% rate in the asymptomatic group
                                      (p < 0.001)

                                      Cerebral protection
                                      4,221 cases performed with cerebral protection – there was a stroke
                                      and procedure related death rate of 2.23% with a total stroke and
                                      death rate of 2.85%
                                         • Symptomatic patients had a 2.70% stroke and procedure-
                                             related death rate with a total stroke and death rate of 3.22%
                                         • Asymptomatic patients had a 1.75% stroke and procedure-
                                             related death rate with a total stroke and death rate of 2.51%

                                      6,753 procedures without cerebral protection – there was a 5.29%
                                      stroke and procedure-related death rate with a total stroke and
                                      death rate of 6.15%
                                          • Symptomatic patients had a 6.04% stroke and procedure-
                                              related death rate with a total stroke and death rate of 6.93%
                                          • Asymptomatic patients had a 3.97% stroke and procedure-
                                              related death rate with a total stroke and death rate of 4.78%


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Abbreviation used: CAS – coronary artery stenting; CEA – carotid endarterectomy; OR – odds ratio; CI – 95% confidence interval; TIA – trans ischaemic attack
Study details                   Key efficacy findings                                                  Key safety findings                    Comments

                                       Restenosis (yearly)
                                       9,419 (85%) patients have been followed
                                       Rates of Restenosis greater than 50% were 2.7%, 2.6%, 2.4% and
                                       5.6% for 12–48 months after stent placement

                                       New neurological events (denominator 9,419 patients)
                                       The rates for 12–48 months were 1.2%, 1.3%, 1.7% and 4.5%
Mckevitt et al (2002) 12               Outcomes reported: stroke/death, major stroke/all death and major                Complications (all patients)            Over the time of this study the
UK                                     disabling stroke/all death                                                       • 12 patients (3.6%) groin              technique has evolved from
                                                                                                                           haematoma                            angioplasty alone to stenting
January 1993–September                 30-day outcomes                                                                  • 1 patient (0.3%) had a allergy to     with protection devices
2002                                    Outcome                   Angioplasty          Stenting           Stenting with    contrast
                                                                                                          protection    • 1 patient (0.3%) had sinus            All patients were on antiplatelet
Patients treated by carotid             All stroke/death           6/86 (7%)               15/150(10%)    5/97 (5.2%)      arrest at time of balloon dilation   therapy following the
angioplasty with or without             Major stroke/              3/86 (3.5%)             10/150 (7%)    4/97 (4.1%) • 1 patient (0.3%) had                    procedure
stenting, for symptomatic               death                                                                              haemostatic plug device
(ischaemic carotid territory            Disabling                  2/86 (2.3%)             6/150 (4%)     2/97 (2.1%)      complication                         Procedures conducted with
event of less than 6 months),           stroke/death                CI (0.3-8.2)           CI (1.5-8.5)   CI (0.3-7.2)                                          two endovascular practitioners
high grade (> 70% stenosis)             Disabling stroke/          2/86 (2.3%)             5/150 (3.3%)   0                                                     and an independent
carotid artery disease                  stroke death                                                                                                            neurologist
secondary to atherosclerosis            Disabling                  2/86 (2.3%)             3/1506 (2%)    0
                                        ischaemic stroke/                                                                                                       All patients were assessed
86 patients had angioplasty             stroke death                                                                                                            prior to treatment and at 30
alone                                   None of these differences are significantly different                                                                   days following the procedure
150 stent without cerebral                                                                                                                                      by an independent neurologist
protection                             There were three non-stroke related deaths due to myocardial
97 patients with cerebral              infarction; gastro-intestinal haemorrhage and a pacemaker insertion-                                                     29 patients were lost to follow-
protection                             related death.                                                                                                           up at 1 year – no details given
                                       1 year follow-up (277 procedures)                                                                                        as to which group these
Mean age 67.6 years (range             • Stroke rate all patients 2.8% (7 procedures)                                                                           patients belonged to
45–88 years)                           • Ipsilateral stroke rate was 0.8% (2 procedures)

Mean time to treatment: 3.6            Duplex examination was available for 238 procedures – 17.6% had
months                                 > 50% restenosis/total occlusion, 6.7% had > 70% restenosis/total
                                       occlusion and 2.9% had a total occlusion
Follow-up: 12 months                   21 patients were documented as having a 50–79% stenosis.
                                       Therefore the 70–100% restenosis is potentially 15.5%.




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Validity and generalisability of the studies
     Endovascular therapy has evolved considerably; from undertaking angioplasty alone to
     using stents in addition to angioplasty, and now the use of stenting with or without
     cerebral protection devices. Therefore it is possible that early studies on stenting may not
     reflect current complication rates.
     This change in practice is evident in many of the studies included in this overview for
     example the CAVATAS study6. In this study 74% (n = 158) of patients were treated
     patients with balloon angioplasty, with only 26% of patients (n = 55) treated with
     angioplasty and stenting.
     Baseline characteristics of patients included in the studies also varied.
     Some of the studies included both asymptomatic and symptomatic patients. These
     groups are known to have differential complication rates. However, many of the outcomes
     in these studies were not examined separately for these patient groups.
     These points (heterogeneity) are highlighted in the Cochrane review on this procedure as
     limitations when interpreting the evidence on this procedure.
     The Cochrane review also included and compared data from completed and stopped
     trials. By including stopped trial data there is a potential that the risks associated with
     endovascular treatment may be over-estimated. The authors of the review note that for
     one of these stopped trials the results included in the review should be regarded as
     provisional (they are unpublished). However, a sensitivity analysis was not undertaken.
     Restenosis rates and risk of subsequent stroke are also not reported in the majority of
     studies.
     There is also a suggestion of a learning curve associated with this procedure.


Analysis of potential literature pool

     There is a significant amount of literature published on this procedure, much of which is
     case series evidence.
     This additional literature can be broadly divided into three groups (some are listed in
     Appendix A of this overview)
               -    angioplasty with and without stenting
               -    angioplasty and stenting without cerebral protection
               -    angioplasty and stenting with cerebral protection.
     Some studies evaluating angioplasty and stenting without cerebral protection may have
     been excluded from the main data extraction tables in preference for those studies that
     assessed this procedure with protection. It is possible that these excluded studies may
     have had longer term data than those included in the main tables but would not have
     reflected the evolving nature of the procedure and the associated risks and benefits.
     Given the change in clinical practice over the last few years it is perhaps unlikely that
     these case series studies will add much to the evidence base on this procedure –
     particularly as there are a number of large randomised controlled trials underway that are
     looking at long-term outcomes and reflect current clinical practice.
     While some preliminary reports have been published from the ongoing or larger trials
     such as SAPPHIRE, these are still preliminary reports, subject to change and are yet to
     be published in peer-reviewed journals.




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Specialist advisors’ opinions
•    The technology is evolving rapidly
•    Long-term results are unknown
•     There are questions regarding which patients are suitable for the procedure i.e. should
    the procedure be performed to prevent a stroke in an asymptomatic individual or only after
    an individual has presented with a TIA or stroke.
•    Training is important – proctoring available
•    Risk of permanent stroke is potentially much higher during the learning curve
•    Randomised controlled trials are underway comparing stenting and endarterectomy.


Issues for consideration by IPAC
This is a complex area and one that is difficult to capture and assess in an overview given
the changing clinical practice and issues around patient selection.

There are a number of randomised controlled trials underway comparing carotid stenting and
endarterectomy as well as the role of cerebral protection devices (Appendix B for more
details).

The Australian Medical Services Advisory Committee is currently undertaking a systematic
review on carotid stenting. It is anticipated that this review will be available at the end of
2004.




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References
1 ICSS Trial Steering Committee. ICSS: International carotid stenting study protocol. 2003.
  Available: www.ion.ucl.ac.uk/cavatas_icss/protocol.htm

2 Coward LJ, Featherston RL, Brown MM. Percutaneous transluminal angioplasty and stenting for
  carotid artery stenosis (Cochrane review). Cochrane Library 2004;(2).

3 Kastrup A, Groschel K, Krapf H, Brehm BR, Dichgans J, Schulz JB. Early outcome of carotid
  angioplasty and stenting with and without cerebral protection devices: a systematic review of the
  literature.[see comment]. [Review] [71 refs]. Stroke 2003; 34(3):813-819.

4 Brooks WH, McClure RR, Jones MR, Coleman TC, Breathitt L. Carotid angioplasty and stenting
  versus carotid endarterectomy: randomized trial in a community hospital.[see comment]. Journal
  of the American College of Cardiology 2001; 38(6):1589-1595.

5 Brooks WH, McClure RR, Jones MR, Coleman TL, Breathitt L. Carotid angioplasty and stenting
  versus carotid endarterectomy for treatment of asymptomatic carotid stenosis: a randomized trial
  in a community hospital. Neurosurgery 2004; 54(2):318-324.

6 Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and
  Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial.[see comment].
  Lancet 2001; 357(9270):1729-1737.

7 Naylor AR, Bolia A, Abbott RJ, Pye IF, Smith J, Lennard N et al. Randomized study of carotid
  angioplasty and stenting versus carotid endarterectomy: a stopped trial.[see comment]. Journal of
  Vascular Surgery 1998; 28(2):326-334.

 8 Alberts MJ. Results of a multicenter prospective randomised trial of carotid artery stenting vs
    carotid endarterectomy. Stroke 32, 325. 2001.(Abstract)

9 Alberts MJ MR. A randomized trial of carotid stenting vs endarterectomy in patients with
  symptomatic carotid stenosis: Study design. The Journal of Neurovascular Disease 1997;
  2(6):228-234.

10 CArotid Revascularization with Endarterectomy or Stenting Systems (CARESS): investigator
   selection. Journal of Endovascular Therapy: Official Journal of the International Society of
   Endovascular Specialists 2001; 8(6):547-549.

11 Wholey MH, Al Mubarek N, Wholey MH. Updated review of the global carotid artery stent registry.
   Catheterization & Cardiovascular Interventions 2003; 60(2):259-266.

12 McKevitt FM, Macdonald S, Venables GS, Cleveland TJ, Gaines PA. Complications following
   carotid angioplasty and carotid stenting in patients with symptomatic carotid artery disease.
   Cerebrovascular Diseases 2004; 17(1):28-34.




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Appendix A: Additional studies not included in the summary tables
The following table outlines studies that are considered potentially relevant to the overview
but were not included in the main data extraction table and is by no means an exhaustive list
of potentially relevant studies.


 Article                                         Patients/         Comments               Directions of
                                                 follow up                                conclusions
 Roubin GS, New G, Iyer SS, Vitek                528               Stenting without       The overall 3-day stroke
 JJ, Al Mubarak N, Liu MW et al.                 consecutive       protection             and death rate was
 Immediate and late clinical                     patients                                 7.4%. Over the 5 year
 outcomes of carotid artery stenting                               Symptomatic and        period, the 30 day minor
 in patients with symptomatic and                5 year follow-    asymptomatic           stroke rate improved
 asymptomatic carotid artery                     up                patients               from 7.1% for the first
 stenosis: a 5-year prospective                                                           year to 3.1% for the fifth
 analysis.[see comment]. Circulation                               This paper is          year.
 2001; 103(4):532-537.                                             included in the
                                                                   systematic review by
                                                                   Kastrup et al (2003)
                                                                   (3).
 Bowser AN, Bandyk DF, Evans A,                  27 repeat         Retrospective          Similar outcomes
 Novotney M, Leo F, Back MR et al.               endarectomies     comparison             between procedures
 Outcome of carotid stent-assisted               and 52 stenting
 angioplasty versus open surgical                procedures
 repair of recurrent carotid
 stenosis*1. Journal of Vascular
 Surgery 2003; 38(3):432-438.
 Hobson RW, Lal BK, Chakhtoura E,                105 patients      Stenting with          Authors report a 30 day
 Goldstein J, Haser PB, Kubicka R                                  protection             stroke and death rate of
 et al. Carotid artery stenting:                                                          2.85%
 analysis of data for 105 patients at                              Symptomatic and
 high risk.[see comment][erratum                                   asymptomatic
 appears in J Vasc Surg. 2003                                      patients
 Sep;38(3):497 Note: Chaktoura
 Ellie Y [corrected to Chakhtoura
 Elie Y]]. Journal of Vascular
 Surgery 2003; 37(6):1234-1239.
 Gray WA, White HJ, Jr., Barrett DM,             136 carotid       Non randomised         In hospital outcomes
 Chandran G, Turner R, Reisman M.                stent             comparison –           with carotid stenting
 Carotid stenting and                            procedures        involving costs.       were similar to those
 endarterectomy: a clinical and cost             136                                      with endarterectomy but
 comparison of revascularization                 endarectomies                            were achieved in
 strategies. Stroke 2002; 33(4):1063-                                                     patients with
 1070.                                                                                    significantly more co
                                                                                          morbidities.
 Hanel RA, Xavier AR, Kirmani JF,                Review            Review                 Review
 Yahia AM, Qureshi AI. Management
 of carotid artery stenosis:
 comparing endarterectomy and
 stenting. Current Cardiology
 Reports 2003; 5(2):153-159.




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Appendix B: Ongoing and/or unpublished clinical trials

 Trial no            Study title                                      Study details          Status
 CREST               Carotid Revascularization Endarterectomy         Planned sample         As of March 2004, 840
                     vs Stent Trial                                   size 2500.             patients had been enrolled
                                                                                             and 186 randomized at 55
                     Prospective, randomized, clinical trial.         Carotid artery         centers. Recruitment of
                     Death, stroke, or myocardial infarction at 30    stenting with          patients and centers is
                     days postoperatively; ipsilateral stroke at 60   cerebral protection.   ongoing.
                     days post-operatively.
 EVA-3S              Endarterectomy Versus Angioplasty in             Planned sample         Ongoing as of September
                     patients with Severe Symptomatic carotid         size 1000              2000.
                     Stenosis


                     To compare the efficacy of angioplasty and
                     stenting with that of carotid endarterectomy
                     in the secondary prevention of ischemic
                     stroke.
 ICSS                International Carotid Stenting Study             Planned sample         Recruitment began in 2001
 (CAVATAS 2)         Is a international randomised trial of stroke    size 1500.             and is expected to
                     prevention comparing the effectiveness of                               continue for five years, with
                     treatment of carotid stenosis by carotid         Carotid artery         a planned enrollment of
                     stenting with treatment by carotid               stenting with          2000 patients.
                     endarterectomy.                                  cerebral protection
                                                                                             As of November 2003, 201
                                                                                             patients have been
                                                                                             randomized at 23 centers.
 SPACE               Stent-protected Percutaneous Angioplasty         Planned sample         As of December of 2003,
                     of the Carotid vs. Endarterectomy                size 1900.             581 patients have been
                                                                                             randomized. Recruitment
                                                                                             is ongoing, with an
                     To compare the safety and prophylactic                                  expected enrollment of
                     efficacies of stent-protected percutaneous                              1900 patients at 40
                     angioplasty of the carotid artery (SPAC) and                            centers.
                     carotid endarterectomy (CEA) against stroke
                     and other vascular events in patients with
                     symptomatic carotid stenosis.


 SAPPHIRE            Stenting and Angioplasty with Protection in      Actual study size:     Trial was halted in June
                     Patients and High Risk for Endarterectomy        307                    2002 due to low enrolment.
                                                                                             30 days results presented
                     To compare the safety and efficacy of the                               in February 2003, with 1
                     Cordis Nitinol Carotid Stent with the                                   year follow-up results
                     AngioGuard distal protective device with                                expected in mid 2003.
                     those of carotid endarterectomy in treating
                     carotid artery disease in high-risk patients.
 ARCHER              ACCULINK for Revascularization of Carotids       Non-randomised         Currently recruiting.
                     in High-Risk Patients                            study with a
                                                                      planned enrollment
                     To evaluate the prophylactic efficacy of         of 400 patients at
                     carotid stenting in patients at high risk for    30 centers.
                     stroke who are also poor candidates for
                     conventional carotid endarterectomy.
 MAVErIC             Evaluation of the Medtronic AVE Self-            Planned sample         Recruitment if expected to
                     Expanding Carotid Stent System with D            size 350 patients      begin shortly
                     Protection in the treatment of carotid
                     stenosis
 SHELTER             Stenting of High risk patients Extra cranial     Single-arm,            Recruitment initiated
                     Lesions Trial with Emboli Removal                prospective, multi-    January 2001
                                                                      center study




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Appendix C: Literature search for

The following search strategy was used to identify papers in Medline. A similar strategy was
used to identify papers in EMBASE, Current Contents, PredMedline and all EMB databases.

For all other databases a simple search strategy using the key words in the title was
employed.

#      Search History
1      *Carotid Stenosis/su, th [Surgery, Therapy]
2      *Carotid Arteries/su [Surgery]
3      *Carotid Artery Diseases/su, th [Surgery, Therapy]
4      or/1-3
5      (angioplasty adj2 stent$).tw.
6      *STENTS/ae [Adverse Effects]
7      stent$.tw.
8      *ANGIOPLASTY/
9      7 and 8
       (stent$ adj3 endovascular).mp. [mp=title, original title, abstract, name of substance, mesh
10
       subject heading]
11     5 or 6 or 9 or 10
12     4 and 11
13     exp ENDARTERECTOMY, CAROTID/
14     endarterectomy.tw.
15     13 or 14
16     15 and 12
       (CAS adj5 CEA).mp. [mp=title, original title, abstract, name of substance, mesh subject
17
       heading]
18     (endarterectomy adj2 stent$).ti.
19     (carotid adj2 stent$).ti.
20     (carotid adj2 stenosis).ti.
21     19 and 20
22     16 or 17 or 18 or 21
23     limit 22 to human




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