Journal Journal ClubClub
Ani Balmanoukian Ani Balmanoukian andand
Peter Benjamin Peter Benjamin
November 9, 2006 November 9, 2006
Endarterectomy Endarterectomy versus Stenting in versus Stenting in
Patients with Patients with Symptomatic Severe Symptomatic Severe
Carotid StenosisCarotid StenosisMas et al. Mas et al.
NEJM 355;16 October 19, NEJM 355;16 October 19, 20062006
BackgroundBackground Carotid Endarterectomy is the Carotid Endarterectomy is the
standard treatment for symptomatic standard treatment for symptomatic or asymptomatic high-grade(> 60% or asymptomatic high-grade(> 60% or 70%) internal carotid artery or 70%) internal carotid artery stenosis.stenosis.
Carotid artery stenting has become Carotid artery stenting has become another optionanother option
Carotid EndarterectomyCarotid Endarterectomy
NASCET and ECST NASCET and ECST trials have trials have demonstrated the demonstrated the efficacy in efficacy in symptomatic symptomatic patientspatients
Complications Complications include local nerve include local nerve injury and strokeinjury and stroke
www.vascular.co.nz
Carotid StentingCarotid Stenting
Less invasive than Less invasive than CEACEA
Can be done under Can be done under local anesthesia and local anesthesia and sedationsedation
Less costly than CEALess costly than CEA Risk of stroke and Risk of stroke and
local complicationslocal complications Long term efficacy Long term efficacy
not well known yetnot well known yethttp://radinfo.musc.edu/~stringes/carotidimage25.jpg
Hypothesis/Goal: Hypothesis/Goal: Evaluate whether Evaluate whether stenting is not inferior to stenting is not inferior to endarterectomy with regard to the endarterectomy with regard to the risks of the procedure and long-term risks of the procedure and long-term efficacy in patients with symptomatic efficacy in patients with symptomatic carotid stenosis.carotid stenosis.
Design: Design: Randomized, noninferiority Randomized, noninferiority trial.trial.
Setting: Setting: 20 academic and 10 non-20 academic and 10 non-academic centers in France. academic centers in France.
Investigators: Investigators: Each center had to have a Each center had to have a team of physicians consisting ofteam of physicians consisting of
1 Neurologist1 Neurologist
1 Vascular surgeon: had to have 1 Vascular surgeon: had to have performed at leastperformed at least
25 CEAs25 CEAs
1 Interventional physician: had to have 1 Interventional physician: had to have performed performed
at least 12 carotid stenting at least 12 carotid stenting procedures or at procedures or at
least 35 stenting procedures in the least 35 stenting procedures in the supraaortic trunks, of which 5 supraaortic trunks, of which 5
were in the were in the carotid artery.carotid artery.
Participants:Participants: 527 patients >18 y/o, with 527 patients >18 y/o, with history of a history of a hemispheric or retinal TIA or a hemispheric or retinal TIA or a nondisabling stroke nondisabling stroke within 120 days within 120 days before enrollment.before enrollment.
Stenosis of 60-99% in the symptomatic Stenosis of 60-99% in the symptomatic carotid artery.carotid artery.
Exclusion: disabling stroke, Exclusion: disabling stroke, nonatherosclerotic carotid disease, previous nonatherosclerotic carotid disease, previous revascularization, bleeding disorder, revascularization, bleeding disorder, uncontrolled HTN or diabetes, unstable uncontrolled HTN or diabetes, unstable angina, life expectancy <2 years.angina, life expectancy <2 years.
Figure 1.Mas et al, Endarterectomy vs. stenting in patients with symptomatic severe carotic stenosis. NEJM 2006;355:1660-71
Data Collection: Data Collection: Evaluation by Neurologist at Evaluation by Neurologist at 48 hrs, 30 days, 6 months after treatment and 6 48 hrs, 30 days, 6 months after treatment and 6 months thereafter. months thereafter.
Outcome: Outcome: Primary: Any stroke or death occurring Primary: Any stroke or death occurring
within 30 days after treatment. within 30 days after treatment.
Secondary: MI, TIA, cranial nerve injury, Secondary: MI, TIA, cranial nerve injury, major local complications, and systemic major local complications, and systemic complications within 30 days.complications within 30 days.
Analysis: Analysis: Kaplan-Meier method, intention to Kaplan-Meier method, intention to treat principle. treat principle.
Table 1. Baseline Characteristics of the Patients.
Key Points• Patients overall very similar• Only differences:
• More patients older than 75 yo in CEA group (40.5% vs. 32.2%)• More patients with h/o stroke in CEA group (20.1% vs 12.6%)• Higher proportion of contralateral carotid occlusion in stenting group (none of these had a stroke after stenting)
Table 3: Risk of stroke or death and other outcomes within 30 days
Key Points:• Unadjusted RR of stroke/death is 2.5 for stenting vs CEA (Number Needed to Harm: 17)
• No significant correlation between RR of stroke/death and number of patients treated at each center
• No significant difference in stroke/death outcomes between interventionalists who were experienced, tutored during training, tutored after training
• Decreased incidence in stroke/death in pts who had cerebral protection along with stenting vs stenting alone
• RR stroke/death adjusted for age was 2.4, h/o stroke 2.6
• Cranial nerve injury much more likely with CEA (7.7% vs 1.1%)
Conclusions/ImplicationsConclusions/Implications
In pts with symptomatic carotid stenosis In pts with symptomatic carotid stenosis >60%, CEA has lower rates of >60%, CEA has lower rates of stroke/death through 6 monthsstroke/death through 6 months
These results agree with some (e.g. These results agree with some (e.g. SPACE), but not all (e.g. SAPPHIRE) SPACE), but not all (e.g. SAPPHIRE) prior studiesprior studies
Taken together, pending further Taken together, pending further evidence, stenting should be limited to evidence, stenting should be limited to symptomatic pts with >70% stenosis symptomatic pts with >70% stenosis who are high surgical riskwho are high surgical risk
StrengthsStrengths
Large, Multicenter RCTLarge, Multicenter RCT All patients accounted for at All patients accounted for at
conclusionconclusion Groups were similar at start of trialGroups were similar at start of trial
WeaknessesWeaknesses
Required minimal experience for Required minimal experience for interventionalists doing procedureinterventionalists doing procedure
Didn’t indicate differences in Didn’t indicate differences in complications based on experiencecomplications based on experience
Anesthesiology or periop differences?Anesthesiology or periop differences? No standardization of stenting device No standardization of stenting device
used (5 different stents, 7 different used (5 different stents, 7 different cerebral protection systems used)cerebral protection systems used)
DiscussionDiscussion What are unique aspects of a noninferiority trialWhat are unique aspects of a noninferiority trial What is the significance of an intention to treat What is the significance of an intention to treat
analysisanalysis Intricacies in a surgical rct that are uniqueIntricacies in a surgical rct that are unique
How to minimize differences in How to minimize differences in surgeon/interventionalist experience?surgeon/interventionalist experience?
How to minimize effects of other aspects (e.g. How to minimize effects of other aspects (e.g. anesthesia, postop care, etc)anesthesia, postop care, etc)
Can you standardize experience level differences Can you standardize experience level differences between CEA and carotid stenting?between CEA and carotid stenting?
Any way to blind such a trial?Any way to blind such a trial?
ReferencesReferences
Mas JL et al. Endarterectomy versus Mas JL et al. Endarterectomy versus stenting in patients with symptomatic severe stenting in patients with symptomatic severe carotid stenosis. N Engl J Med. 2006 Oct carotid stenosis. N Engl J Med. 2006 Oct 19;355(16):1660-71. 19;355(16):1660-71.
North American Symptomatic Carotid North American Symptomatic Carotid Endarterectomy Trial Collaborators. Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; carotid stenosis. N Engl J Med 1991; 325:445-53.325:445-53.