Transcript Duplex U/S for the estimation of internal carotid artery

Carotid Endarterectomy versus
Stenting:
Where do we stand today?
Vascular Conference
March 23, 2010
Landmark NIH Clinical Trial Comparing Two Stroke Prevention Procedures
Shows Surgery and Stenting Equally Safe and Effective
Opportunities Exist to Target the Treatment to the Patient
ASA: Stenting Carotid on a Par with Endarterectomy
SVS Responds to the Role of Carotid Studies,
CREST and ICSS, in Stroke Prevention
Carotid Artery Atherosclerotic Disease
• Cerebrovascular disease
affects 750,000 people in US
each year
• Stroke is 3rd leading cause of
death in North America
– 168,000 deaths in US/year
• Treatment:
– Medical therapy
• Aspirin, plavix, statins
• Risk factor modification
– Carotid Endarterectomy
(CEA)
– Carotid artery stenting
(CAS)
North American Symptomatic Carotid Endarterectomy
Trial (NASCET)
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Randomized trial of CEA vs antiplatelet therapy
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50 centers in US and Canada
1987-1996
659 patients with stenosis >70%
2226 patients with stenosis < 70%
Patients:
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30-69% or 70-99%
Defined by angiography
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Surgical treatment:
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Medical treatment as above
CEA
Long-term Result:
– 70-99% group:
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Anti-thrombotic medication
• Mostly aspirin (dose not
specified)
Anti-hypertensive and lipid lowering
agents at the discretion of the
treating physician
Net increase in surgical risk of any
stroke or death of 4.3%
1.4% net increase in disabling
stroke or death
•
Disease limiting life expectancy to <5
years
Medical treatment:
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Carotid artery stenosis:
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Peri-operative stroke or death:
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<80 years old
Non-disabling stroke or retinal or
hemispheric TIA within 120 days
Exclusion:
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CEA had 17% absolute risk
reduction for stroke at 2 years
50-69% group:
• CEA had a 7% absolute risk
reduction at 5 years
– 30-49% group:
• No difference
Conclusions:
– CEA recommended for
symptomatic carotid artery
stenosis of 70-99%
– In centers with low peri-operative
stroke rate and in select patients,
CEA can be utilized for
symptomatic stenosis of 50-69%
NEJM 1991 & 1998
Asymptomatic Carotid Atherosclerosis Study (ACAS)
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Randomized trial of CEA vs antiplatelet therapy
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39 centers in US and Canada
1988-1993
1662 patients
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Medical treatment:
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Patients
– Age 40-79
– Exclusion criteria:
Surgical treatment:
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• Severe comorbidities
• disease likely to cause death
w/in 5 yrs
• Any cerebrovascular event
• Contra-indication to aspirin
Carotid artery stenosis
– >60% stenosis
– Defined by angiography or doppler
US
• Same angiographic definition as
NASCET
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325mg aspirin daily
Recommendations on risk factor
reduction
No angiography required
Aspirin & risk reduction
Angiography required
CEA
Peri-operative risk of stroke or death:
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Surgery: 2.3%
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JAMA 1995
Medical: 0.4%
5-year results:
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5 strokes secondary to angiography
6% absolute risk reduction for stroke
Conclusions:
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CEA recommended for patients with >
60% stenosis
In centers with low peri-operative
mortality and stroke rates (<3%)
In patients with good overall health
Carotid Revascularization Using Endarterectomy or
Stenting Systems (CaRESS)
•
Prospective non-randomized
cohort study
– 14 centers in US
– 397 patients
• 254 CEA, 143 CAS
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– CEA: 2.4%
– CAS: 2.1%
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4 year follow up results:
– Any stroke:
– Standard CEA versus CAS with
cerebral protection device
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Peri-operative stroke or death:
• CEA 9.6%, CAS 8.6%
– Death/ non-fatal stroke:
Patients:
• CEA 26.5%, CAS 21.8%
– Similar patient demographics
• 68% asymptomatic
• >90% with >75% stenosis
• Significantly more prior CEA or
stent in the CAS arm
– Restenosis:
• Significantly higher in CAS arm
•
Conclusion:
– Proof of principle that CAS with
distal protection should be
compared to CEA in a broad
patient sample in a randomized
trial
J Endovasc Ther 2003 & 2009
Protected Carotid-Artery Stenting versus Endarterectomy in
High-Risk Patients (SAPPHIRE)
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Primary end point (death/ stroke/ MI at 30
days or death from neurologic cause w/in
1 yr)
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Symtomatic patients: >50%
Asymptomatic patients: >80%
CAS 12% vs. CEA 20.1% (p=0.05)
Conventional end-point (as above
subtracting MI data)
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No difference
Conclusion:
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NEJM 2004
Not standardized
Results:
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Nitinol stent with distal cerebral protection
device
CEA:
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Patients were randomized if the team
agreed that either CEA or CAS was
appropriate
At least one comorbidity that would
deem them high risk for CEA
Duplex US:
CAS: plavix 24hrs pre-op & for 2-4wks
CEA: No plavix
CAS:
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29 centers
334 patients randomized
Patients:
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All patients started on aspirin
Plavix:
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These patients are being operated on in
clinical practice
Multi-center randomized trial
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Procedures:
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The NASCET and ACAS trials exclude
high risk patients
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Principle:
CAS is not inferior to CEA for patients
considered high risk for CEA
Carotid artery stenting compared with endarterectomy in patients with
symptomatic carotid stenosis (International Carotid Senting Study)
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Randomized controlled trial multicenter trial
– 50 centers from Europe/ Australia/ Canada/ New Zealand
– 1713 patients randomized
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Patients:
– Included if >50% stenosis w/ symptoms attributable to the carotid disease
– Exclusion:
• Massive stroke
• Previous CEA or stent on affected side
• Planned CABG or other surgery or contraindication to treatment
– Treating physicians had to agree that either method would be suitable
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Procedures:
– CAS:
• Any trademarked device could be used
• Embolic protection device recommended but not mandatory
• Use of aspirin/ plavix and heparinization recommended
– CEA:
• Technique at the discretion of surgeon
Lancet 2010
Carotid artery stenting compared with endarterectomy in patients with
symptomatic carotid stenosis (International Carotid Senting Study)
Outcomes between initiation of treatment and 30 days
Outcomes between randomization of treatment and 120 days
Carotid artery stenting compared with endarterectomy in patients with
symptomatic carotid stenosis (International Carotid Senting Study)
• Conclusions:
– Carotid endarterectomy is safer than carotid stenting in patients
being treated for symptomatic carotid artery stenosis
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3.3% higher risk of stroke, death, or procedural MI within 120 days
This is mainly due to a higher risk of non-disabling strokes
Rate of disabling stroke or death not significantly different
More cranial nerve palsy and hematoma formation in CEA group
The Carotid Revascularization Endarterectomy versus Stenting
Trial (CREST)
•
Multi-center randomized trial
comparing CEA to CAS in severe
carotid stenosis
– 117 sites in North America
– 2522 patients randomized
• Outcomes released in press
release form
– Composite endpoint (stroke,
death, or MI w/in 30 days)
• CEA 6.8%, CAS 7.2%
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– Any stroke w/in 30 days:
Patients:
– Symptomatic with >50% by angio
or >70% by US/ CTA/ MRI
– Asymptomatic with >60% by
angio, >70% by US, or >80% by
CTA/ MRI
– High risk patients remain eligible
for the study; however, 4 year life
expectancy required
– Octogenarians excluded in midtrial due to stroke/ death rate
• CEA 2.3%, CAS 4.1%
– Major stroke < 1% for both
– MI
• CEA 2.3%, CAS 1.1%
– MI resulted in better quality of
life than stroke
– Ipsilateral stroke w/in 2 yrs
• Equivalent
• CEA 2.4%, CAS 2.0%
J Stroke & Cerebrovasc Dis 2010, Stroke 2010
Conclusions
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Carotid endarterectomy has been established as the gold standard for
treatment of carotid artery stenosis
– NASCET and ACAS trials
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Carotid stenting remains to be proven as a viable alternative to
endarterectomy in all patients
– SAPPHIRE results suggest that CAS is at least equivalent to CEA in high risk
patients
– ICSS results suggest that CAS may cause higher peri-operative morbidity in
symptomatic patients
– CREST results suggest equivalency of CAS to CEA for all patients with carotid
stenosis for composite endpoint of death / stroke/ MI
• However, stroke is more common in CAS, and has a greater impact on quality of life,
that MI
Future Directions
• NASCET and ACAS studies compared CEA to “best medical
treatment”
– Aspirin utilized in both
– Plavix and statins used at the discretion of the treating physician
• Statins in only 14% of patients in NASCET
• Statins have subsequently been associated with decreased
incidence of stroke
– 29% relative reduction in stroke in one large meta-analysis
• JAMA 1997
– Risk ratio of 0.82 [95% CI 0.76 – 0.90] for fatal or non-fatal stroke in
another large meta-analysis
• Am J Med 2004
• Future studies needed to re-assess CEA and CAS in light of optimal
medical management
References
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Barnett et. al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe
stenosis. NEJM 1998; 339: 1415-1425.
Briel et. al. Effects of statins on stroke prevention in patients with and without coronary heart disease: a
meta-analysis of randomized controlled trials. Am J Med 2004; 117(8): 596-606.
CaRESS Steering Committee. Carotid Revascularization Using Endarterectomy or Stenting Systems
(CaRESS): Phase I Clinical Trial. J Endovasc Ther 2003; 10: 1021-1030.
Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for
asymptomatic Carotid Artery Stenosis. JAMA; 273(18): 1421-1428.
Hebert et al. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of
randomized trials. JAMA 1997; 278(4): 313-321.
Hopkins et. al. The Carotid Revascularization Endarterectomy versus Stenting Trial: Credentialling of
Interventionalists and Final Results of Lead-in Phase. Journal of Cerebrovascular Diseases 2010; 19(2):
153-162
International Carotid Stenting Study Investigators. Carotid artery stenting compared with endarterectomy
in patients with symptomatic carotid stenosis (International Carotid Senting Study): an interim analysis of
a randomized controlled trial. Lancet 2010; 375: 985-997
North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effects of carotid
endarterectomy in symptomatic patients with high grade carotid stenosis. NEJM 1991; 325: 445-453.
Sheffet et al. Design of the Carotid Revascularization Endarterectomy versus Stenting Trial. Stroke 2010;
5: 40-46.
Yadev et al. Protected Carotid-Artery Stenting versus Endarterectomy in High-Risk patients. NEJM 2004;
351: 1493-1501.
Zarin et al. Carotid Revascularization Using Endarterectomy or Stenting Systems (CaRESS): Four year
outcomes. J Endovasc Ther 2009; 16: 397-409.