How should we determine the best treatment for patients with asymptomatic carotid stenosis?

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Inzitari D, Eliasziw M, Gates P, et al. The causes and risk of stroke in patients with asymptomatic carotid artery stenosis. N Engl J Med 2000; 342:1693-700.


BACKGROUND: It is unclear whether patients with carotid stenosis and no symptoms benefit from endarterectomy. The authors of this study examined data from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) on patients from 1988 to 1997 with unilateral symptomatic carotid stenosis and asymptomatic contralateral stenosis. The goal was to learn what happened to the asymptomatic stenoses during the follow-up period.

POPULATION STUDIED: The authors studied 1820 patients with asymptomatic carotid stenosis, of whom 1604 had less than a 60% stenosis and 216 had a stenosis between 60% and 99%. The mean age was 66 years; 68% were men. Comorbidities were common: 60% had hypertension, 22% had diabetes mellitus, 36% had a history of myocardial infarction or angina, and 24% had evidence of a clinically silent brain infarction in the territory of the asymptomatic carotid artery (but were still considered asymptomatic for this study).

STUDY DESIGN AND VALIDITY: The NASCET trial enrolled 2885 total patients with a recent transient ischemic attack or a nondisabling ischemic stroke, and randomized them to medical care alone or medical care and endarterectomy. All patients were appropriately evaluated at baseline with carotid angiograms and computed tomography or magnetic resonance imaging of the brain. Patients received follow-up care every 4 months for 5 years. Data in the study was centrally reviewed, and ischemic strokes were classified by underlying cause. Patients were ineligible if they had a cardiac source of embolism or a disease likely to cause death within 5 years.For this analysis, the researchers excluded patients with a history of bilateral carotid symptoms, surgery on the asymptomatic carotid artery, those who had no available angiograms of the asymptomatic artery, and those with either complete occlusion or no evidence of disease in the internal carotid artery. This left a final population of 1820 patients with carotid artery stenosis and no symptoms in the distribution of that vessel. Appropriate risk analysis was performed using Kaplan-Meier curves. A secondary analysis was done using Cox proportional hazard regression modeling to determine whether different risk factors were associated with the 3 causes of stroke.

OUTCOMES MEASURED: The primary outcome measured was the risk of first stroke at 5 years in both the symptomatic and asymptomatic arteries, stratified by the degree of stenosis and the etiology of the stroke (large artery, embolic, or lacunar).

RESULTS: Patients with an asymptomatic stenosis had approximately half the risk of stroke of those with a symptomatic stenosis. The risk of stroke over 5 years among patients with asymptomatic stenosis was 8% for patients with less than 60% stenosis, 14.8% for those with 60% to 74% stenosis, 18.5% for those with 75% to 94% stenosis, and 14.7% for those with 95% to 99% stenosis. Approximately 80% of the first strokes were not preceded by any symptoms of a transient ischemic attack. Almost half the strokes in patients with asymptomatic carotid artery disease had causes other than large artery disease. This information was used to adjust estimates of the benefit of endarterectomy from the Asymptomatic Carotid Atherosclerotic Study. The absolute risk reduction for any stroke during 5 years of follow-up in surgically treated patients is 5.9%; the corresponding risk reduction is only 3.5% for large artery stroke. To prevent 1 large artery stroke at 5 years, 29 patients would have to undergo carotid endarterectomy. This benefit must be balanced against an operative risk of 3% in the hands of the best surgeons, compared with a 4% to 5% risk reported in published series that were less stringently designed.


This study has several important caveats for our patients with symptomatic and asymptomatic carotid artery disease. First, the risk of stroke is substantially lower in patients with asymptomatic carotid artery disease than in those who are symptomatic. Also, approximately 50% of strokes that occur in the territory of the asymptomatic carotid artery do not have their origin in the large artery. The greatest risk of large artery stroke appears to be among patients with a high degree of stenosis, a history of diabetes mellitus, and a history of silent brain infarct beyond the asymptomatic lesion. Finally, the high risk of perioperative death or stroke makes it important that we focus our efforts on doing risk factor screening and properly treating the important risks once identified.