Transcript Practice Parameter: Treatment of Postherpetic Neuralgia
Assessment: 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 © 2005 American Academy of Neurology Published in
Neurology
2005;65:794-801 February 25, 2004
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© 2005 American Academy of Neurology February 25, 2004
Objective
• 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.
guideline
Neurology
1990;40:682) (Updates previous • Additional clinical scenarios, such as use of CE combined with cardiac surgery (CABG), are also reviewed.
© 2005 American Academy of Neurology February 25, 2004
Introduction
• 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.
© 2005 American Academy of Neurology February 25, 2004
Methods
• 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. © 2005 American Academy of Neurology February 25, 2004
Methods
• 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. © 2005 American Academy of Neurology February 25, 2004
AAN Strength of Evidence
Class I Class II
Evidence provided by a prospective study in a broad spectrum of persons with the suspected condition, using a “gold standard” for case definition, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy. In addition, there must be adequate accounting for drop-outs with numbers sufficiently low to have minimal potential for bias Evidence provided by a prospective study of a narrow spectrum of persons with the suspected condition, or a well designed retrospective study of a broad spectrum of persons with an established condition (by “gold standard”) compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy © 2005 American Academy of Neurology February 25, 2004
AAN Strength of Evidence
Class III
Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation.
Class IV
Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls). © 2005 American Academy of Neurology February 25, 2004
Translation of Evidence to Recommendation Level
Level A Level B
Level A = Established as useful/predictive or not useful/predictive for the given condition in the specified population Level B = Probably useful/predictive or not useful/predictive for the given condition in the specified population Level A rating requires at least one convincing class I study or at least two consistent, convincing class II studies Level B rating requires at least one convincing class II study or at least three consistent class III studies © 2005 American Academy of Neurology February 25, 2004
Translation of Evidence to Recommendation Level
Level C Level U
Level C = Possibly useful/predictive or not useful/predictive for the given condition in the specified population Level C rating requires at least two convincing and consistent class III studies Level U = Data inadequate or conflicting. Given current knowledge, test/predictor is unproven © 2005 American Academy of Neurology February 25, 2004
Clinical Question
Does CE benefit symptomatic and asymptomatic patients?
© 2005 American Academy of Neurology February 25, 2004
Author/ Year NASCET Collab. 1991
Stenosis= 70-99%
Analysis of the Evidence
Symptomatic patients Ipsilateral Stroke risk plus periop stroke & death CE + BMT=9% BMT=26% Periop stroke & death Periop disabling stroke & death Any stroke 5.8% 3.3% 2.7% 0.9% 12.6
27.6
Major stroke or death 8.0% 18.1% ECST Collab. Group 1991
Stenosis= 70-99%
CE+BMT=9.5% BMT = 13.6% BMT = best medical therapy © 2005 American Academy of Neurology 7.5% NA 3.7% NA NA NA 4.8% 8.4% February 25, 2004
Author/ Year
Analysis of the Evidence
Symptomatic patients Ipsilateral Stroke risk plus periop stroke & death CE + BMT=4.4% BMT=7.1% Periop stroke & death 6.5% 2.2% Periop disabling stroke & death Any stroke 4.4% 0% NA NA Major stroke or death NA NA Mayberg 1991
Stenosis= 50-99%
ECST Collab. Group 1996
Stenosis= 50-69%
NASCET collab.1998
Stenosis= 50-69%
CE + BMT=NA BMT=NA CE + BMT=1.9% BMT=7.0% © 2005 American Academy of Neurology NA NA 22.2% 15.7% 7.9% NA NA 16.8% 14.2% NA NA 19.8% 26.4% 14.9% 20.1% February 25, 2004
Author/ Year
Analysis of the Evidence
Symptomatic patients Ipsilateral Stroke risk plus periop stroke & death Periop stroke & death NA NA Periop disabling stroke & death Any stroke 8.0% NA 16.2% 10.4% Major stroke or death NA NA ECST Collab. Group 1996
Stenosis= 30-49%
CE + BMT=NA BMT=NA ECST Collab. Group 1991, 1998
Stenosis= 0-29%
CE+BMT=11.3% BMT=5.6% Rothwell 2003
Stenosis=
CE+BMT=NA BMT=NA
<50%
© 2005 American Academy of Neurology 3.3% 0 6.7% NA 1.7% 0 % NA NA 17.1% 12.8% NA NA 36.7% 30.7% NA NA February 25, 2004
Clinical Question
Does CE benefit asymptomatic patients?
© 2005 American Academy of Neurology February 25, 2004
Analysis 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 © 2005 American Academy of Neurology February 25, 2004
Analysis 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 © 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Asymptomatic patients • Asymptomatic Carotid Atherosclerosis Study (ACAS) – 1662 patients, 60-99% stenosis angiographically proven 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 © 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Asymptomatic 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% © 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Asymptomatic patients • Asymptomatic Carotid Atherosclerosis Study (ACAS) – The perioperative stroke rate = 2.3%, NNH=43 – 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 (n=1512, stroke and death = 4.6%) © 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Asymptomatic 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 February 25, 2004
Analysis of the Evidence
Asymptomatic 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 © 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Asymptomatic patients • Asymptomatic Carotid Surgery Trial (ACST) – Subgroup analyses showed • benefits were significant for those < 65 years, those between 65 and 74 years, but uncertain for those > 75 years • Men and women both benefited but there were only a total of 40 non-perioperative strokes in women so the results were not as definite (
p
=0.02) • 5 year benefit of CE appeared to be as great for those with <80% diameter reduction (mean 69% stenosis) as for those with 80-99% (mean 87%) reduction • No significant difference in results in those patients who were never symptomatic compared to those with symptoms > six months previously (7.1% and 4.6% absolute five year gain, respectively) © 2005 American Academy of Neurology February 25, 2004
Clinical Question
Is emergent CE beneficial in patients with progressing stroke of <24 hours?
© 2005 American Academy of Neurology February 25, 2004
•
Analysis of the Evidence
Emergent 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 © 2005 American Academy of Neurology February 25, 2004
Clinical Question
What are the most important clinical variables that impact the risk/benefit ratio?
© 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Clinical 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 © 2005 American Academy of Neurology February 25, 2004
Clinical Question
What are the most important radiologic factors that impact the risk/benefit ratio?
© 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Radiologic 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) © 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Radiologic 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.
© 2005 American Academy of Neurology February 25, 2004
Clinical Question
What is the ideal dose of aspirin preoperatively in patients undergoing CE?
© 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Aspirin 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 © 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Aspirin 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 © 2005 American Academy of Neurology February 25, 2004
Clinical Question
What are the data regarding CE concurrent with or prior to CABG?
© 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
CABG • 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.
© 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
CABG Author/ Year Group Periop stroke % 0 Periop MI % 3.9
Ennix, 1979 Class III Ennix, 1979 Class III Simultaneous CE-CABG Staged CABG then CE Carrel, 1992 Class III Carrel, 1992 Class III Simultaneous CE-CABG Staged CE then CABG Takach, 1997 Class III Simultaneous CE-CABG Takach, 1997 Staged CE then Class III CABG © 2005 American Academy of Neurology 0 1.9
0 3.9
1.9
2.4
0 8.8
4.7
4.7
Periop death % 5.9
Long term survival NR 1.2
3.8
4.4
3.5
1.6
NR 91 at 6 yrs 87 at 6 yrs NR NR February 25, 2004
Analysis of the Evidence
CABG Author/ Year Group Periop stroke % Periop MI % Periop death % 5.3
Hertzer, 1997 Class IV Kaul, 2000 Class IV Minami, 2000 Class IV Evageloupoulos, 2000 Class IV Simultaneous CE-CABG 4.3
Simultaneous CE-CABG 1.4 within 3 Months NA Simultaneous CE-CABG 3.2
Simultaneous CE-CABG 2.2
0 0.6
3.2
3.4
2.6
8.9
Long term survival NR NR 79 at 5 yrs NR © 2005 American Academy of Neurology February 25, 2004
Clinical Question
How long should one wait after a stroke to perform CE?
© 2005 American Academy of Neurology February 25, 2004
Analysis of the Evidence
Time 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 < 6 weeks from the stroke. • 2 studies defined early surgery as < four weeks from the stroke.
• None of the studies found differences in the outcomes in terms of operative morbidity and longer-term follow-up. © 2005 American Academy of Neurology February 25, 2004
Recommendations
Stenosis (%) 70-99% Use of Carotid Endarterectomy in Symptomatic Patients Recommendation CE is established as effective for recently symptomatic (within previous 6 months) patients with 70-99% ICA angiographic stenosis (
Level A
).
50-69% •CE may be considered for patients with 50-69% symptomatic stenosis (
Level B
) but the clinician should consider additional clinical and angiographic variables (
Level C
) . See tables
below.
•It is recommended that the patient have at least a five year life expectancy and that the peri-operative stroke/death rate should be <6% for symptomatic patients (
Level A).
<50% •CE should not be considered for symptomatic patients with <50% stenosis (
Level A
).
•Medical management is preferred to CE for symptomatic patients with <50% stenosis (
Level A
).
© 2005 American Academy of Neurology February 25, 2004
Recommendations
Stenosis (%) Use of Carotid Endarterectomy in Asymptomatic Patients Recommendation 60-99% It is reasonable to consider CE for patients between the ages of 40-75 years and with asymptomatic stenosis of 60-99% if the patient has an expected five year life expectancy and if the surgical stroke or death frequency can be reliably documented to be <3% (
Level A
). The five year life expectancy is important since peri-operative strokes pose an up front risk to the patient and the benefit from CE emerges only after a number of years. © 2005 American Academy of Neurology February 25, 2004
Recommendations
Patient Variables to Consider in Carotid Endarterectomy Decision-making Patient variables Recommendation Symptomatic women Women with 50-69% symptomatic stenosis did not show clear benefit in previous trials (
Level C
). Patients w/ hemispheric TIA or stroke •Patients with hemispheric TIA or stroke had greater benefit from CE than patients with retinal ischemic events (
Level C
). •Patients operated on within two weeks of their last TIA or mild stroke derive greater benefit from CE (
Level C
). Progressing neurological deficit •No recommendation can be provided regarding the value of emergent CE in patients with a progressing neurological deficit ( © 2005 American Academy of Neurology
Level U
). February 25, 2004
Recommendations
Radiologic Factors to Consider in Carotid Endarterectomy Decision-making
Radiologic Factors Contralateral occlusion in symptomatic patients Recommendation Contralateral occlusion is associated with increased operative risk but persistent benefit (
Level C
). Contralateral occlusion in asymptomatic patients Contralateral occlusion erases the small benefit of CE in asymptomatic patients (
Level C
).
Near-occlusion in symptomatic patients CE for patients with angiographic near-occlusion in symptomatic patients is associated with a trend toward benefit at two years but not associated with a clear long-term benefit (
Level C
). © 2005 American Academy of Neurology February 25, 2004
Peri operative aspirin
Recommendations
• •
Reviewed Clinical Scenarios
Symptomatic and asymptomatic patients undergoing CE should be given aspirin (81 or 325 mg/day) prior to surgery and for at least 3-months following surgery to reduce the combined endpoint of stroke, myocardial infarction, and death (
Level A
). Although data are not available, it is recommended that aspirin (81 or 325 mg/day) be continued indefinitely provided that contraindications are absent. Aspirin at 650 or 1300 mg/day is less effective in the peri-operative period. The data are insufficient to recommend the use of other anti-platelet agents in the peri-operative setting. © 2005 American Academy of Neurology February 25, 2004
Recommendations
Recent TIA or non disabling stroke • •
Reviewed Clinical Scenarios
For patients with severe stenosis and a recent TIA or nondisabling stroke, CE should be performed without delay, preferably within two weeks of the patient’s last symptomatic event (
Level C
). There is insufficient evidence to support or refute the performance of CE within four to six weeks of a recent moderate to severe stroke (
Level U
).
CE prior to or concurrent with CABG At this time the available data are insufficient to declare either CE before or simultaneous with CABG as superior in patients with concomitant carotid and coronary artery occlusive disease (
Level U
).
© 2005 American Academy of Neurology February 25, 2004
Recommendations 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. © 2005 American Academy of Neurology February 25, 2004
Recommendations 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. © 2005 American Academy of Neurology February 25, 2004
Disclaimer
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.
© 2005 American Academy of Neurology February 25, 2004
Acknowledgments
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.
© 2005 American Academy of Neurology February 25, 2004
TTA 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 © 2005 American Academy of Neurology February 25, 2004
To view the entire guideline and additional AAN guidelines visit:
www.aan.com/guidelines
Published in
Neurology
2005;65:794-801 © 2005 American Academy of Neurology February 25, 2004