Title: Assessment: Carotid Endarterectomy An EvidenceBased Review
1Assessment Carotid Endarterectomy?An
Evidence-Based Review
- Report of the Therapeutics and Technology
Subcommittee of the American Academy of
Neurology - S Chaturvedi MD, A Bruno MD, T Feasby MD, R
Holloway MD, O Benavente MD, SN Cohen MD, R Cote
MD, D Hess MD, J Saver MD, JD Spence MD, B Stern
MD, J Wilterdink MD - Published in Neurology 200565794-801
2Objective
- The objective of this report is to provide an
updated statement on the efficacy of carotid
endarterectomy (CE) for stroke prevention in
asymptomatic and symptomatic patients with
internal carotid artery stenosis. (Updates
previous guideline Neurology 199040682) - Additional clinical scenarios, such as use of CE
combined with cardiac surgery (CABG), are also
reviewed.
3Introduction
- Depending on the population, extracranial
internal carotid artery (ICA) stenosis accounts
for 15-20 of ischemic strokes. - CE is the most frequently performed operation to
prevent stroke. - Since 1990 guideline, several multi-center trials
have been completed. This statement reflects an
update on major developments.
4Methods
- Vascular neurologists were appointed by the
Therapeutics and Technology Assessment
Subcommittee (TTA) of the AAN. - Nine clinical questions were identified and
selected due to clinical importance. - A systematic search was performed for articles
from 1990-2001. - Additional articles from 2002-2004 were included
using pre-specified criteria.
5Methods
- Case reports, review articles, technical studies,
and single surgeon case series were excluded. - After exclusions, total of 186 articles were
reviewed independently by 2 committee members. - Number needed to treat (NNT) and number needed to
harm (NNH) were evaluated in studies. - Recommendations generated based on application of
levels of evidence to the abstracted articles
using AAN schemes.
6AAN Strength of Evidence
7AAN Strength of Evidence
8Translation of Evidence to Recommendation Level
9Translation of Evidence to Recommendation Level
10Clinical Question
- Does CE benefit symptomatic and asymptomatic
patients?
11Analysis of the EvidenceSymptomatic patients
12Analysis of the EvidenceSymptomatic patients
13Analysis of the EvidenceSymptomatic patients
14Clinical Question
- Does CE benefit asymptomatic patients?
15Analysis of the Evidence Asymptomatic patients
- 3 Class I studies are available
- Asymptomatic Carotid Atherosclerosis Study
(ACAS), Veterans Affairs Study, Asymptomatic
Carotid Surgery Trial (ACST) - 2 other studies were completed or planned but
were stopped prematurely or had a suboptimal
study design - Mayo Clinic trial stopped due to a high rate of
MI (22) in the surgical group, CASANOVA
16Analysis of the Evidence Asymptomatic patients
- The Veterans Affairs study
- 444 men with angiographically-proven 50-99
asymptomatic stenosis - Nonsignficant trend favoring CE for prevention of
ipsilateral stroke (9.4 vs. 4.7 at 4 years) - Primary endpoint transient ischemic attack
(TIA) - The 30 day perioperative stroke and death rate
was 4.7, NNH 21
17Analysis of the EvidenceAsymptomatic patients
- Asymptomatic Carotid Atherosclerosis Study (ACAS)
- 1662 patients, 60-99 stenosis angiographically-pr
oven for the surgical group primarily-proven with
ultrasound for the medical group - Enrollment 1993-2003 with planned10 year
follow-up - Eligibility carotid artery diameter reduction
of at least 60,no symptoms within the past six
months - Patients were randomized to best medical TX (BMT)
or BMT CE
18Analysis of the EvidenceAsymptomatic patients
- Asymptomatic Carotid Atherosclerosis Study (ACAS)
- Study stopped after 2.7 years median follow-up
5.9 ARR at 5 years favoring CE (NNT 17) - 5 year projected rate of ipsilateral stroke
- medically treated patients 11.0
- surgically treated patients 5.1
- relative risk reduction 53
- 5 year projected rate for major ipsilateral
stroke any perioperative major ipsilateral stroke - medically treated patients 6.0
- surgical patients 3.4
19Analysis of the EvidenceAsymptomatic patients
- Asymptomatic Carotid Atherosclerosis Study (ACAS)
- The perioperative stroke rate 2.3, NNH43
- Such a low perioperative stroke/death rate has
not been achieved in most recent observational
studies or in the Aspirin and Carotid
Endarterectomy (ACE) trial (n1512, stroke and
death 4.6)
20Analysis of the EvidenceAsymptomatic patients
- Asymptomatic Carotid Surgery Trial (ACST)
- Randomized study of immediate vs. indefinite
deferral of CE - 5 five year follow-up at 126 centers in 30
countries - diameter reduction stenosis by carotid
ultrasound - Eligibility carotid artery diameter reduction
of at least 60 on ultrasound and no symptoms
within the past six months - Enrollment 1993 2003 planned 10 year follow-up
- 3120 randomized patients - 2 groups of 1560 each
21Analysis of the EvidenceAsymptomatic patients
- Asymptomatic Carotid Surgery Trial (ACST)
- Perioperative events (stroke and death within 30
days) and the non-perioperative strokes combined - Net 5 year risks were 6.4 (immediate CE) versus
11.8 (deferred CE) for all strokes 3.5 vs.
6.1 for fatal or disabling strokes - Gain mostly in non-perioperative carotid
territory ischemic strokes - The benefit was seen in both contralateral and
ipsilateral carotid-territory strokes
22Analysis of the EvidenceAsymptomatic patients
- Asymptomatic Carotid Surgery Trial (ACST)
- Subgroup analyses showed
- benefits were significant for those lt 65 years,
those between 65 and 74 years, but uncertain for
those gt 75 years - Men and women both benefited but there were only
a total of 40 non-perioperative strokes in women
so the results were not as definite (p0.02) - 5 year benefit of CE appeared to be as great for
those with lt80 diameter reduction (mean 69
stenosis) as for those with 80-99 (mean 87)
reduction - No significant difference in results in those
patients who were never symptomatic compared to
those with symptoms gt six months previously (7.1
and 4.6 absolute five year gain, respectively)
23Clinical Question
- Is emergent CE beneficial in patients with
progressing stroke of lt24 hours?
24Analysis of the EvidenceEmergent CE
- Four Class IV studies met the criteria
- In 3 studies, neurological improvement was noted
in 81-93 of patients who underwent emergent CE - Studies were fairly small in size, lacked
objective evaluation of the reported neurological
outcomes, and one study was clouded by coexisting
treatments including emergent thrombolysis
25Clinical Question
- What are the most important clinical variables
that impact the risk/benefit ratio?
26Analysis of the EvidenceClinical Variables
- None of the trials had clinical variables that
impact risk/benefit as predetermined endpoints - In post-hoc analyses 2 variables stand out
gender and nature of the presenting symptoms - In NASCET 50-69 stenosis group ACAS no benefit
shown for CE in women - NASCET showed lower subsequent stroke risk in
patients w/ retinal ischemia compared to patients
with hemispheric events - A pooled analysis of the 3 symptomatic studies
identified modifiers of CE benefit. Greatest
benefit in men, patients above age 75 years, and
those randomized within 2 weeks of their last
symptomatic event
27Clinical Question
- What are the most important radiologic factors
that impact the risk/benefit ratio?
28Analysis of the EvidenceRadiologic Factors
- Several studies addressed issues (status of the
contralateral carotid artery, angiographic
appearance of the ICA, and other factors). - NASCET and ACAS studies had highest level data on
contralateral occlusion. - For symptomatic patients
- Contralateral occlusion present surgical
complication rate is higher than if the
contralateral ICA is patent - Better outcome compared to medical management for
patients with 70-99 stenosis - For asymptomatic patients
- Contralateral occlusion present randomized
evidence suggests that patients do slightly
better with medical management (2.0 absolute
increase in risk with CE at 5 years)
29Analysis of the EvidenceRadiologic Factors
- For patients with angiographic near-occlusion
- Pooled analysis of the symptomatic studies
suggests - CE is associated with trend toward benefit at 2
years but no clear benefit at 5 years - BMT severe stenosis patients in NASCET-including
those with near-occlusion-were offered CE after
the 2 year results made available - Only Class IV evidence or below available for
other factors such as influence of carotid siphon
stenosis or posterior circulation stenosis.
30Clinical Question
- What is the ideal dose of aspirin preoperatively
in patients undergoing CE?
31Analysis of the EvidenceAspirin therapy
- Aspirin and Carotid Endarterectomy trial (ACE)
- 2,849 subjects, double-blind randomized clinical
trial - Compared aspirin before carotid endarterectomy
continued for 3 months at doses 81 mg, 325 mg,
650 mg and 1300 mg - Primary outcome combined rate of stroke,
myocardial infarction, and death was the - Outcome lower in the low-dose groups (81 mg and
325 mg) than in the high-dose groups (650 mg and
1300 mg) at 30 days and 3 months -
32Analysis of the EvidenceAspirin therapy
- Another trial enrolled 232 subjects to 75mg
aspirin or placebo before CE and continued for 6
months. - Aspirin compared with placebo Trial demonstrated
fewer strokes without recovery in those subjects
randomized aspirin at 1 month and 6 months
33Clinical Question
- What are the data regarding CE concurrent with or
prior to CABG?
34Analysis of the EvidenceCABG
- 48 studies for review, nine met criteria for
inclusion (50 subjects). - No randomized clinical trials addressing this
question the best available evidence comes from
retrospective case control (class III) and case
series (class IV) reports. - Some studies compared findings between groups
with different surgical strategies, but because
prospective criteria were not applied, a
selection bias is likely.
35Analysis of the EvidenceCABG
36Analysis of the EvidenceCABG
37Clinical Question
- How long should one wait after a stroke to
perform CE?
38Analysis of the EvidenceTime to CE surgery
- 6 retrospective cohort studies comparing timing
of CE in patients after a stroke. Significant
limitations in the designs of these studies. - 4 of the studies defined early surgery as lt 6
weeks from the stroke. - 2 studies defined early surgery as lt four weeks
from the stroke. - None of the studies found differences in the
outcomes in terms of operative morbidity and
longer-term follow-up.
39Recommendations
40Recommendations
41Recommendations
42Recommendations
43Recommendations
44Recommendations
45Recommendations for Future Research
- Improve quality of data is needed
- The setting of urgent CE in patients with
progressing stroke - The appropriateness of CE in community settings
- The management of coexisting carotid and coronary
artery disease - The timing of CE in patients with recent stroke.
- Data are needed on newer antiplatelet agents in
the perioperative setting - Data are needed on how CE compares to less
invasive, endovascular treatment with stenting in
patients with symptomatic and asymptomatic
carotid stenosis.
46Recommendations for Future Research
- Data are needed on the role of cerebral
hemodynamics in risk stratification for patients
with carotid stenosis. - Data are needed to examine indices of
vasoreactivity and cerebral perfusion in future
studies of patients with both symptomatic and
asymptomatic carotid stenosis. - There is a paucity of data on stroke rates in
patients with carotid stenosis who receive an
aggressive treatment regimen with statins, newer
antiplatelet agents, and targeted blood pressure
lowering.
47Disclaimer
- This statement is provided as an educational
service of the American Academy of Neurology. It
is based on an assessment of current scientific
and clinical information. It is not intended to
include all possible proper methods of care for a
particular neurological problem or all legitimate
criteria for choosing to use a specific
procedure. Neither is it intended to exclude any
reasonable alternative methodologies. The AAN
recognizes that specific patient care decisions
are the prerogative of the patient and the
physician caring for the patient, based on all of
the circumstances involved.
48Acknowledgments
- The committee thanks Drs. Chung Hsu and David
Lefkowitz as liaisons from the TTA Subcommittee,
Alison Nakashima, Paul Hetland, Nancy King, and
Wendy Edlund from the American Academy of
Neurology for their superb assistance in
coordinating the review, and Vicki Glasgow for
assistance with the literature search.
49TTA Subcommittee Members
- Therapeutics and Technology Assessment
Subcommittee Members - Douglas S. Goodin, MD (Chair) Yuen T. So, MD,
PhD (Vice-Chair) Carmel Armon, MD Richard M.
Dubinsky, MD Mark Hallett, MD David Hammond,
MD Cynthia Harden, MD Chung Hsu, MD, PhD
(ex-officio) Andres M. Kanner, MD (ex-officio)
David S. Lefkowitz, MD Janis Miyasaki, MD
Michael A. Sloan, MD James C. Stevens, MD
50To view the entire guideline and additional AAN
guidelines visit www.aan.com/professionals/prac
tice/index/cfm
- Published in Neurology 200565794-801