Journal Club Ani Balmanoukian and Peter Benjamin November 9, 2006 Journal Club Ani Balmanoukian and Peter Benjamin November 9, 2006

Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis Mas et al. NEJM 355;16 October 19, 2006

Background Carotid Endarterectomy is the standard treatment for symptomatic or asymptomatic high-grade(> 60% or 70%) internal carotid artery stenosis. Carotid Endarterectomy is the standard treatment for symptomatic or asymptomatic high-grade(> 60% or 70%) internal carotid artery stenosis. Carotid artery stenting has become another option Carotid artery stenting has become another option

Carotid Endarterectomy NASCET and ECST trials have demonstrated the efficacy in symptomatic patients NASCET and ECST trials have demonstrated the efficacy in symptomatic patients Complications include local nerve injury and stroke Complications include local nerve injury and stroke

Carotid Stenting Less invasive than CEA Less invasive than CEA Can be done under local anesthesia and sedation Can be done under local anesthesia and sedation Less costly than CEA Less costly than CEA Risk of stroke and local complications Risk of stroke and local complications Long term efficacy not well known yet Long term efficacy not well known yet

Hypothesis/Goal: Evaluate whether stenting is not inferior to endarterectomy with regard to the risks of the procedure and long-term efficacy in patients with symptomatic carotid stenosis. Hypothesis/Goal: Evaluate whether stenting is not inferior to endarterectomy with regard to the risks of the procedure and long-term efficacy in patients with symptomatic carotid stenosis. Design: Randomized, noninferiority trial. Design: Randomized, noninferiority trial. Setting: 20 academic and 10 non-academic centers in France. Setting: 20 academic and 10 non-academic centers in France.

Investigators: Each center had to have a team of physicians consisting of Investigators: Each center had to have a team of physicians consisting of 1 Neurologist 1 Vascular surgeon: had to have performed at least 25 CEAs 1 Interventional physician: had to have performed at least 12 carotid stenting procedures or at least 35 stenting procedures in the supraaortic trunks, of which 5 were in the carotid artery.

Participants: 527 patients >18 y/o, with history of a hemispheric or retinal TIA or a nondisabling stroke within 120 days before enrollment. Participants: 527 patients >18 y/o, with history of a hemispheric or retinal TIA or a nondisabling stroke within 120 days before enrollment. Stenosis of 60-99% in the symptomatic carotid artery. Stenosis of 60-99% in the symptomatic carotid artery. Exclusion: disabling stroke, nonatherosclerotic carotid disease, previous revascularization, bleeding disorder, uncontrolled HTN or diabetes, unstable angina, life expectancy <2 years.

Figure 1. Mas et al, Endarterectomy vs. stenting in patients with symptomatic severe carotic stenosis. NEJM 2006;355:

Data Collection: Evaluation by Neurologist at 48 hrs, 30 days, 6 months after treatment and 6 months thereafter. Data Collection: Evaluation by Neurologist at 48 hrs, 30 days, 6 months after treatment and 6 months thereafter. Outcome: Outcome: Primary: Any stroke or death occurring within 30 days after treatment. Secondary: MI, TIA, cranial nerve injury, major local complications, and systemic complications within 30 days. Analysis: Kaplan-Meier method, intention to treat principle. Analysis: Kaplan-Meier method, intention to 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/Implications In pts with symptomatic carotid stenosis >60%, CEA has lower rates of stroke/death through 6 months In pts with symptomatic carotid stenosis >60%, CEA has lower rates of stroke/death through 6 months These results agree with some (e.g. SPACE), but not all (e.g. SAPPHIRE) prior studies These results agree with some (e.g. SPACE), but not all (e.g. SAPPHIRE) prior studies Taken together, pending further evidence, stenting should be limited to symptomatic pts with >70% stenosis who are high surgical risk Taken together, pending further evidence, stenting should be limited to symptomatic pts with >70% stenosis who are high surgical risk

Strengths Large, Multicenter RCT Large, Multicenter RCT All patients accounted for at conclusion All patients accounted for at conclusion Groups were similar at start of trial Groups were similar at start of trial

Weaknesses Required minimal experience for interventionalists doing procedure Required minimal experience for interventionalists doing procedure Didn’t indicate differences in complications based on experience Didn’t indicate differences in complications based on experience Anesthesiology or periop differences? Anesthesiology or periop differences? No standardization of stenting device used (5 different stents, 7 different cerebral protection systems used) No standardization of stenting device used (5 different stents, 7 different cerebral protection systems used)

Discussion What are unique aspects of a noninferiority trial What are unique aspects of a noninferiority trial What is the significance of an intention to treat analysis What is the significance of an intention to treat analysis Intricacies in a surgical rct that are unique Intricacies in a surgical rct that are unique How to minimize differences in surgeon/interventionalist experience? How to minimize differences in surgeon/interventionalist experience? How to minimize effects of other aspects (e.g. anesthesia, postop care, etc) How to minimize effects of other aspects (e.g. anesthesia, postop care, etc) Can you standardize experience level differences between CEA and carotid stenting? Can you standardize experience level differences between CEA and carotid stenting? Any way to blind such a trial? Any way to blind such a trial?

References Mas JL et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med Oct 19;355(16): Mas JL et al. Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis. N Engl J Med Oct 19;355(16): North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325: North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 1991; 325: