Sténoses Carotidiennes Symptomatiques - Symptomatic Carotid Stenoses

1. Rothwell PM et al. Reanalysis of the final results of the European Carotid Surgery Trial. Stroke 2003;34:514-523
2. Cunningham EJ et al. Long-term durability of carotid endarterectomy for symptomatic stenosis and risk factors for late postoperative stroke. Stroke 2002;33:2658-2663
3. Ballotta E et al. Carotid endarterectomy contralateral to carotid artery occlusion: analysis from a randomized study. Langenbecks Arch Surg 2002;387:216-221
4. Rothwell PM, Warlow CP: Low risk of ischemic stroke in patients with reduced internal carotid artery lumen diameter distal to severe symptomatic carotid stenosis: cerebral protection due to low poststenotic flow? On behalf of the European Carotid Surgery Trialists' Collaborative Group. Stroke 2000;31:622-630
5. Inzitari D et al. The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 2000;342:1693-1700
6. Paciaroni M et al. Medical complications associated with carotid endarterectomy. North American Symptomatic Carotid Endarterectomy Trial (NASCET). Stroke 1999;30:1759-1763
7. Ferguson GG et al. The North American Symptomatic Carotid Endarterectomy Trial: surgical results in 1415 patients. Stroke 1999;30:1751-1758.
8. Barnett HJ et al. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1998;339:1415-1425.
9. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379-1387
10. Morgenstern LB et al. The risks and benefits of carotid endarterectomy in patients with near occlusion of the carotid artery. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. Neurology 1997;48:911-915
11. Paddock-Eliasziw LM et al. Long-term prognosis and the effect of carotid endarterectomy in patients with recurrent ipsilateral ischemic events. North American Symptomatic Carotid Endarterectomy Trial Group. Neurology 1996;47:1158-1162
12. Gasecki AP et al. Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. J Neurosurg 1995;83:778-782
13. Eliasziw M et al. Prognosis for patients following a transient ischemic attack with and without a cerebral infarction on brain CT. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. Neurology 1995;45:428-431
14. Haynes RB et al. Prevention of functional impairment by endarterectomy for symptomatic high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Jama 1994;271:1256-1259
15. Gasecki AP et al. Early endarterectomy for severe carotid artery stenosis after a nondisabling stroke: results from the North American Symptomatic Carotid Endarterectomy Trial. J Vasc Surg 1994;20:288-295
16. Eliasziw M, et al. Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial. Stroke 1994;25:304-308.
17. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group. Lancet 1991;337:1235-1243
18. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991;325:445-453.

1. Rothwell PM, Gutnikov SA, Warlow CP: Reanalysis of the final results of the European Carotid Surgery Trial. Stroke 2003;34:514-523.
BACKGROUND AND PURPOSE: The European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET) have shown that endarterectomy reduces the risk of stroke in certain patients with recently symptomatic carotid stenosis. However, they differed in the degree of stenosis above which surgery was reported to be effective. This disparity has led to inconsistent clinical recommendations but may have been due to differences between the trials in the methods of measurement of carotid stenosis and definitions of outcome events. METHODS: To allow direct comparison of analyses from ECST and NASCET, we remeasured the prerandomization ECST carotid angiograms and redefined the outcome events the same way as in NASCET. RESULTS: We randomized 3018 patients and followed them up for a mean of 73 months. Surgery reduced the 5-year risk of any stroke or surgical death by 5.7% (95% CI, 0 to 11.6) in patients with 50% to 69% stenosis (n=646, P=0.05) and by 21.2% (95% CI, 12.9 to 29.4) in patients with 70% to 99% stenosis without "near occlusion" (n=429, P<0.0001). These benefits were maintained at the 10-year follow-up. However, surgery was of no benefit in patients (n=125) with near occlusion. The effect of surgery in this group was highly significantly different from that in patients with 70% to 99% stenosis without near occlusion (P=0.002). Surgery was harmful in patients with <30% stenosis (n=1321, P=0.007) and of no benefit in patients with 30% to 49% stenosis (n=478, P=0.6). CONCLUSIONS: Results of the ECST and NASCET were consistent when analyzed in the same way. In ECST, surgery was highly beneficial for 70% to 99% stenosis and moderately beneficial for 50% to 69% stenosis. However, contrary to clinical recommendations and current practice, surgery was of little benefit in patients with carotid near occlusion.

2. Cunningham EJ, Bond R, Mehta Z, Mayberg MR, Warlow CP, Rothwell PM: Long-term durability of carotid endarterectomy for symptomatic stenosis and risk factors for late postoperative stroke. Stroke 2002;33:2658-2663.
BACKGROUND AND PURPOSE: Carotid endarterectomy (CEA) reduces the risk of stroke ipsilateral to recently symptomatic severe carotid stenosis. Other techniques such as percutaneous transluminal angioplasty with stenting are currently being compared with CEA. Thus far, case series and several small, randomized, controlled trials of CEA versus percutaneous transluminal angioplasty (with and without stenting) have focused primarily on the 30-day procedural risks of stroke and death. However, long-term durability is also important. To determine the long-term risk of stroke after CEA and to identify risk factors, we studied patients in the European Carotid Study Trial (ECST), the largest published cohort with long-term follow-up by physicians after CEA. METHODS: Risks of ipsilateral carotid territory ischemic stroke were calculated by Kaplan-Meier analysis starting on the 30th day after CEA in 1728 patients who underwent trial surgery. Risk factors were determined by Cox regression. For comparison, we also determined the "background" risk of stroke on medical treatment in the ECST in the territory of 558 previously asymptomatic contralateral carotid arteries with <30% angiographic stenosis (ECST method) at randomization. RESULTS: The risks of disabling ipsilateral ischemic stroke and any ipsilateral ischemic stroke were constant after CEA, reaching 4.4% [95% confidence interval (CI), 3.0 to 5.8] and 9.7% (95% CI, 7.6 to 11.7), respectively, by 10 years. The equivalent ischemic stroke risks distal to contralateral <30% asymptomatic carotid stenoses were 1.9% (95% CI, 0.8 to 3.2) and 4.5% (95% CI, 1.5 to 7.4). Presentation with cerebral symptoms, diabetes, elevated systolic blood pressure, smoking, male sex, increasing age, and a lesser severity of preoperative stenosis were associated with an increased risk of late stroke after CEA, but plaque morphology and patch grafting were not. CONCLUSIONS: Although the risk of late ipsilateral ischemic stroke after CEA for symptomatic stenosis is approximately double the background risk in the territory of <30% asymptomatic stenosis, it is still only approximately 1% per year and remains low for at least 10 years after CEA. This is the standard against which alternative treatments should be judged. Several risk factors may be useful in identifying patients at particularly high risk of late postoperative stroke.

3. Ballotta E, Da Giau G, Baracchini C: Carotid endarterectomy contralateral to carotid artery occlusion: analysis from a randomized study. Langenbecks Arch Surg 2002;387:216-221.
BACKGROUND AND AIMS: Many studies have reported the benefits of carotid endarterectomy (CEA) contralateral to an occluded internal carotid artery (ICA), with varying results. This study analyzed perioperative and late outcomes in a recent trial in which patients were randomized to carotid eversion endarterectomy (CEE) or traditional CEA with patching (CEAP). PATIENTS AND METHODS: In 336 primary CEAs (310 patients) 68 were contralateral to an occluded ICA (group I). The remaining 268 CEAs served as control group (group II). All patients underwent clinical follow-up and duplex ultrasonography at 1, 6, and 12 months and every year thereafter. Endpoints of the study were early and late neurological events, and deaths. RESULTS: Group I had a significantly higher incidence of perioperative electroencephalic changes and need for shunting. The perioperative stroke rate in group I was almost three times as high as in group II, but the difference was not significant. Similarly, the perioperative minor neurological event and death rates, as with the cumulative stroke-free and survival rates at 1, 3, and 5 years, were comparable in the two groups. CONCLUSIONS: CEA contralateral to an occluded ICA can be implemented with perioperative stroke and mortality rates and late stroke-free and survival rates comparable to CEA with no contralateral ICA occlusion.

4. Rothwell PM, Warlow CP: Low risk of ischemic stroke in patients with reduced internal carotid artery lumen diameter distal to severe symptomatic carotid stenosis: cerebral protection due to low poststenotic flow? On behalf of the European Carotid Surgery Trialists' Collaborative Group. Stroke 2000;31:622-630.
BACKGROUND AND PURPOSE: Patients with recently symptomatic severe carotid stenosis have a high risk of ischemic stroke on medical treatment. The main mechanism of stroke appears to be plaque surface thrombus formation and distal embolism. It is unclear to what extent reduction in blood flow across the stenosis, and the consequent reduction in cerebral perfusion pressure, is also important. Angiographic indices of reduced cerebral perfusion may identify patients at a particularly high risk of stroke who require urgent endarterectomy. The most direct angiographic correlate of poststenotic perfusion pressure is the degree of narrowing of the distal internal carotid artery (ICA) lumen. We sought to develop criteria for the definition of poststenotic narrowing of the ICA and to determine the effect of this and other angiographic characteristics likely to be associated with reduced cerebral perfusion on the risk of ipsilateral ischemic stroke in patients with recently symptomatic carotid stenosis. METHODS: We studied the carotid angiograms of 3007 patients in the European Carotid Surgery Trial. Poststenotic narrowing of the ICA was defined with use of the ratio of the lumen diameter of the ICA to that of the common carotid artery (CCA). The normal range of the ICA/CCA ratio was defined in 2966 symptomatic or contralateral carotid arteries with 0% to 49% stenosis. Arteries with 70% to 99% symptomatic stenosis and an ICA/CCA ratio below this range were categorized as narrowed. We related the presence of narrowing and other angiographic characteristics to the risk of ipsilateral ischemic stroke on medical treatment. RESULTS: An assessment of the ICA/CCA ratio had good interobserver reproducibility. Poststenotic narrowing of the ICA was defined as an ICA/CCA ratio of <0.42. The 5-year risk of ipsilateral carotid territory ischemic stroke on medical treatment was 8% in patients with 70% to 99% stenosis and narrowing of the ICA versus 25% in patients without narrowing (log rank test, P=0.02). This difference remained after correction for other clinical and angiographic variables (hazard ratio 0.40, 95% CI 0.17 to 0.94, P=0. 03). The other angiographic characteristics did not predict stroke. CONCLUSIONS: Poststenotic narrowing of the ICA was associated with a low risk of stroke on medical treatment. This suggests that low flow alone is not usually sufficient to cause ischemic stroke distal to symptomatic carotid stenosis. Poststenotic narrowing may be protective because blood flow distal to the stenosis is insufficient to carry emboli to the brain.

5. Inzitari D, Eliasziw M, Gates P, Sharpe BL, Chan RK, Meldrum HE, Barnett HJ: The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 2000;342:1693-1700.
BACKGROUND: The causes of stroke in patients with asymptomatic carotid-artery stenosis have not been carefully studied. Information about causes might influence decisions about the use of carotid endarterectomy in such patients. METHODS: We studied patients with unilateral symptomatic carotid-artery stenosis and asymptomatic contralateral stenosis from 1988 to 1997. The causes, severity, risk, and predictors of stroke in the territory of the asymptomatic artery were examined and quantified. RESULTS: The risk of stroke at five years after study entry in a total of 1820 patients increased with the severity of stenosis. Among 1604 patients with stenosis of less than 60 percent of the luminal diameter, the risk of a first stroke was 8.0 percent (1.6 percent annually), as compared with 16.2 percent (3.2 percent annually) among 216 patients with 60 to 99 percent stenosis. In the group with 60 to 99 percent stenosis, the five-year risk of stroke in the territory of a large artery was 9.9 percent, that of lacunar stroke was 6.0 percent, and that of cardioembolic stroke 2.1 percent. Some patients had more than one stroke of more than one cause. In the territory of an asymptomatic occluded artery (as was identified in 86 patients), the annualized risk of stroke was 1.9 percent. Strokes with different causes had different risk factors. The risk factors for large-artery stroke were silent brain infarction, a history of diabetes, and a higher degree of stenosis; for cardioembolic stroke, a history of myocardial infarction or angina and hypertension; for lacunar stroke, age of 75 years or older, hypertension, diabetes, and a higher degree of stenosis. CONCLUSIONS: The risk of stroke among patients with asymptomatic carotid-artery stenosis is relatively low. Forty-five percent of strokes in patients with asymptomatic stenosis of 60 to 99 percent are attributable to lacunes or cardioembolism. These observations have implications for the use of endarterectomy in asymptomatic patients. Without analysis of the risk of stroke according to cause, the absolute benefit associated with endarterectomy may be overestimated.

6. Paciaroni M, Eliasziw M, Kappelle LJ, Finan JW, Ferguson GG, Barnett HJ: Medical complications associated with carotid endarterectomy. North American Symptomatic Carotid Endarterectomy Trial (NASCET). Stroke 1999;30:1759-1763.
BACKGROUND AND PURPOSE: Carotid endarterectomy (CE) has been shown to be beneficial in patients with symptomatic high-grade (70% to 99%) internal carotid artery stenosis. To achieve this benefit, complications must be kept to a minimum. Complications not associated with the procedure itself, but related to medical conditions, have received little attention. METHODS: Medical complications that occurred within 30 days after CE were recorded in 1415 patients with symptomatic stenosis (30% to 99%) of the internal carotid artery. They were compared with 1433 patients who received medical care alone. All patients were in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). RESULTS: One hundred fifteen patients (8.1%) had 142 medical complications: 14 (1%) myocardial infarctions, 101 (7.1%) other cardiovascular disorders, 11 (0.8%) respiratory complications, 6 (0.4%) transient confusions, and 10 (0.7%) other complications. Of the 142 complications, 69.7% were of short duration, and only 26.8% prolonged hospitalization. Five patients died: 3 from myocardial infarction and 2 suddenly. Medically treated patients experienced similar complications with one third the frequency. Endarterectomy was approximately 1.5 times more likely to trigger medical complications in patients with a history of myocardial infarction, angina, or hypertension (P<0.05). CONCLUSIONS: Perioperative medical complications were observed in slightly fewer than 1 of every 10 patients who underwent CE. The majority of these complications completely resolved. Most complications were cardiovascular and occurred in patients with 1 or more cardiovascular risk factors. In this selected population, the occurrence of perioperative myocardial infarction was uncommon.

7. Ferguson GG, Eliasziw M, Barr HW, Clagett GP, Barnes RW, Wallace MC, Taylor DW, Haynes RB, Finan JW, Hachinski VC, Barnett HJ: The North American Symptomatic Carotid Endarterectomy Trial: surgical results in 1415 patients. Stroke 1999;30:1751-1758.
BACKGROUND AND PURPOSE: This study reports the surgical results in those patients who underwent carotid endarterectomy in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). METHODS: The rates of perioperative stroke and death at 30 days and the final assessment of stroke severity at 90 days were calculated. Regression modeling was used to identify variables that increased or decreased perioperative risk. Nonoutcome surgical complications were summarized. The durability of carotid endarterectomy was examined. RESULTS: In 1415 patients there were 92 perioperative outcome events, for an overall rate of 6.5%. At 30 days the results were as follows: death, 1.1%; disabling stroke, 1.8%; and nondisabling stroke, 3.7%. At 90 days, because of improvement in the neurological status of patients judged to have been disabled at 30 days, the results were as follows: death, 1.1%; disabling stroke, 0.9%; and nondisabling stroke, 4.5%. Thirty events occurred intraoperatively; 62 were delayed. Most strokes resulted from thromboembolism. Five baseline variables were predictive of increased surgical risk: hemispheric versus retinal transient ischemic attack as the qualifying event, left-sided procedure, contralateral carotid occlusion, ipsilateral ischemic lesion on CT scan, and irregular or ulcerated ipsilateral plaque. History of coronary artery disease with prior cardiac procedure was associated with reduced risk. The risk of perioperative wound complications was 9.3%, and that of cranial nerve injuries was 8.6%; most were of mild severity. At 8 years, the risk of disabling ipsilateral stroke was 5.7%, and that of any ipsilateral stroke was 17.1%. CONCLUSIONS: The overall rate of perioperative stroke and death was 6.5%, but the rate of permanently disabling stroke and death was only 2.0%. Other surgical complications were rarely clinically important. Carotid endarterectomy is a durable procedure.

8. Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, Rankin RN, Clagett GP, Hachinski VC, Sackett DL, Thorpe KE, Meldrum HE, Spence JD: Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1998;339:1415-1425.
BACKGROUND: Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. METHODS: Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were available for 99.7 percent of the patients. The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent randomization. RESULTS: Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. CONCLUSIONS: Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke. Decisions about treatment for patients in this category must take into account recognized risk factors, and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed. Patients with stenosis of less than 50 percent did not benefit from surgery. Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

9. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379-1387.
BACKGROUND: Our objective was to assess the risks and benefits of carotid endarterectomy, primarily in terms of stroke prevention, in patients with recently symptomatic carotid stenosis. METHODS: This multicentre, randomised controlled trial enrolled 3024 patients. We enrolled men and women of any age, with some degree of carotid stenosis, who within the previous 6 months had had at least one transient or mild symptomatic ischaemic vascular event in the distribution of one or both carotid arteries. Between 1981 and 1994, we allocated 1811 (60%) patients to surgery and 1213 (40%) to control (surgery to be avoided for as long as possible). Follow-up was until the end of 1995 (mean 6.1 years), and the main analyses were by intention to treat. FINDINGS: The overall outcome (major stroke or death) occurred in 669 (37.0%) surgery-group patients and 442 (36.5%) control-group patients. The risk of major stroke or death complicating surgery (7.0%) did not vary substantially with severity of stenosis. On the other hand, the risk of major ischaemic stroke ipsilateral to the unoperated symptomatic carotid artery increased with severity of stenosis, particularly above about 70-80% of the original luminal diameter, but only for 2-3 years after randomisation. On average, the immediate risk of surgery was worth trading off against the long-term risk of stroke without surgery when the stenosis was greater than about 80% diameter; the Kaplan-Meier estimate of the frequency of a major stroke or death at 3 years was 26.5% for the control group and 14.9% for the surgery group, an absolute benefit from surgery of 11.6%. However, consideration of variations in risk with age and sex modified this simple rule based on stenosis severity. We present a graphical procedure that should improve the selection of patients for surgery. INTERPRETATION: Carotid endarterectomy is indicated for most patients with a recent non-disabling carotid-territory ischaemic event when the symptomatic stenosis is greater than about 80%. Age and sex should also be taken into account in decisions on whether to operate.

10. Morgenstern LB, Fox AJ, Sharpe BL, Eliasziw M, Barnett HJ, Grotta JC: The risks and benefits of carotid endarterectomy in patients with near occlusion of the carotid artery. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. Neurology 1997;48:911-915.
Some believe that carotid endarterectomy (CEA) for carotid near occlusion is a necessary emergency procedure while others call it dangerous. We used the North American Symptomatic Carotid Endarterectomy Trial (NASCET) data to perform an observational study to examine the safety and benefit of CEA for carotid near occlusion. We divided the data of 659 patients into stenosis groups: 70 to 79%, 80 to 89%, 90 to 94%, and near occlusion. The 106 carotid-near-occlusion patients were subdivided into those with a string-like lumen (n = 29) and those without a string-like lumen (n = 77). Of the 48 patients with near occlusion treated with CEA, 3 (6.3%) had perioperative strokes, similar to the 70-94% stenosis group. Only 1 of 58 patients (1.7%) with near occlusion treated medically had a stroke in the first month, suggesting that CEA is not needed on an emergency basis in this circumstance. For medically treated patients, the 1-year risk of stroke increases with escalating degrees of carotid stenosis, where the risk is 35.1% for patients with 90-94% stenosis. For patients with near occlusion, the 1-year stroke risk diminishes to 11.1%, which approximates the risk for patients with 70-89% stenosis. A comparison of treatment differences indicates that surgery reduces the risk of stroke at 1 year by approximately one-half (p < 0.001), regardless of the degree of stenosis or the subcategory of carotid near occlusion (p = 0.89). Our data suggest that CEA is beneficial for near occlusion and not more dangerous than in patients with 70-94% stenosis, provided that the procedure is performed by an experienced surgeon with a low complication rate.

11. Paddock-Eliasziw LM, Eliasziw M, Barr HW, Barnett HJ: Long-term prognosis and the effect of carotid endarterectomy in patients with recurrent ipsilateral ischemic events. North American Symptomatic Carotid Endarterectomy Trial Group. Neurology 1996;47:1158-1162.
BACKGROUND AND PURPOSE: The present study examines how the prognosis of patients who present with an ischemic event (TIA or nondisabling stroke) referable to a 70 to 99% carotid artery stenosis is modified by the pattern of their ischemic history. We also examined the benefits of performing carotid endarterectomy on the recently symptomatic artery. METHODS: A total of 608 patients was divided into two groups. The recent group (N = 444) consisted of patients who became newly symptomatic within the previous 6 months of their presenting event. Prior to this, they were asymptomatic. The recurrent group (N = 164) consisted of patients who had one or more ischemic events within the previous 6 months of their presenting event, as well as one or more within the previous 7 to 12 months. All events were ipsilateral to the presenting event. RESULTS: Kaplan-Meier risk estimates of ipsilateral stroke at 2 years for medically treated patients were 18.6 +/- 3.3% in the recent group and 41.2 +/- 6.9% in the recurrent group (p = 0.0002, logrank test). For patients who underwent carotid endarterectomy, the risks were 7.8 +/- 2.0% and 10.8 +/- 3.4% (p = 0.36, logrank test). Multivariate analyses did not identify any baseline patients characteristics as confounders nor any statistical interactions. CONCLUSIONS: There is a need for urgency in considering carotid endarterectomy for patients with 70 to 99% carotid artery stenosis who have had recurrent ipsilateral ischemic events extending back more than 6 months. These patients are at more than twice the risk of stroke as those who are newly symptomatic.

12. Gasecki AP, Eliasziw M, Ferguson GG, Hachinski V, Barnett HJ: Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. J Neurosurg 1995;83:778-782.
The purpose of this study was to examine how the prognosis of patients who presented with a recent ischemic event referable to a 70% to 99% stenosis of one carotid artery (ipsilateral) was altered by stenosis and occlusion of the contralateral carotid artery. The benefit of performing carotid endarterectomy on the recently symptomatic artery, in the presence of contralateral artery disease, was also examined. A total of 659 patients were grouped into one of three categories according to the extent of stenosis in the contralateral carotid artery: less than 70% (559 patients), 70% to 99% (57 patients), and occlusion (43 patients). Strokes that occurred during the follow-up period were designated as ipsilateral if they arose from the same carotid artery as the symptom for which the patient had been entered into the study. Medically treated patients with an occluded contralateral artery were more than twice as likely to have had an ipsilateral stroke at 2 years than patients with either severe (hazard ratio: 2.36; 95% confidence interval (CI): 1.00-5.62) or mild-to-moderate (hazard ratio: 2.65; 95% CI: 1.43-4.90) contralateral artery stenosis. The perioperative risk of stroke and death was higher in patients with an occluded contralateral artery (4.0% risk) or mild-to-moderate (5.1% risk) contralateral stenosis. Regression analyses indicated that the results were not affected by other risk factors. An occluded contralateral carotid artery significantly increased the risk of stroke associated with a severely stenosed ipsilateral carotid artery. Despite higher perioperative morbidity in the presence of an occluded contralateral artery, the longer-term outlook for patients who had endarterectomy performed on the recently symptomatic, severely stenosed ipsilateral carotid artery was considerably better than for medically treated patients.

13. Eliasziw M, Streifler JY, Spence JD, Fox AJ, Hachinski VC, Barnett HJ: Prognosis for patients following a transient ischemic attack with and without a cerebral infarction on brain CT. North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. Neurology 1995;45:428-431.
BACKGROUND: Although cerebral infarctions are commonly observed on brain CTs of patients with TIAs, their prognostic importance is unknown. METHOD: The association between appropriately sited brain infarctions (ie, lesions located in the anterior circulation of the brain and ipsilateral to the symptomatic stenosed carotid artery) visualized on CT and the risk of subsequent stroke was assessed by Cox proportional hazards regression in 164 patients presenting with TIA (and no history of previous stroke) and severe angiographically defined carotid stenosis (70 to 99%) from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Patients with a TIA and CT-verified brain lesions were older and were more likely to have higher degrees of carotid stenosis and carotid plaque ulceration, a longer duration of symptoms, and a history of hypertension. With regard to prognosis, after adjusting for all known risk factors (patient characteristics) in a regression analysis, the presence of ischemic lesions observed on CT was not associated with an increased risk of ipsilateral stroke at 2 years (adjusted hazard ratio = 1.00; 95% CI: 0.39 to 2.58; p value = 0.99). CONCLUSION: Considered in combination with other patient characteristics, the mere presence of an appropriately sited cerebral infarction on CT does not alter the prognosis (risk of ipsilateral strokes) of severely stenosed patients with TIA. Therefore, there is no clinical rationale in differentiating patients with TIA on the basis of CT findings alone.

14. Haynes RB, Taylor DW, Sackett DL, Thorpe K, Ferguson GG, Barnett HJ: Prevention of functional impairment by endarterectomy for symptomatic high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Jama 1994;271:1256-1259.
OBJECTIVE--To determine whether carotid endarterectomy prevents deterioration of functional status among patients with transient ischemic attacks or nondisabling strokes and ipsilateral carotid stenosis of 70% to 99%. DESIGN--Multicentered randomized controlled trial with an average 18-month follow-up. SETTING--Fifty clinical centers in North America. PATIENTS--A total of 659 patients presenting with recent transient attacks of nondisabling stroke and ipsilateral atherosclerotic carotid stenosis of 70% to 99% were included. Patients were stable neurologically at the time of entry. No patient was lost to follow-up. INTERVENTION--Vascular surgeons and neurosurgeons were prescreened for low perioperative complication rates. Patients were randomly allocated to carotid endarterectomy plus continuing medical care (n = 328) or medical care alone (n = 331), including antiplatelet therapy. MAIN OUTCOME MEASURES--All patients were assessed by neurologists for the occurrence of stroke and functional status at scheduled intervals after entry. RESULTS--In addition to a previously reported risk reduction for ipsilateral stroke for patients assigned to carotid endarterectomy, there was an absolute risk reduction (and relative risk reduction [RRR]) for functional status impairment of 5.6% (RRR, 69%) for vision, 4.6% (RRR, 87%) for comprehension of language, 8.3% (RRR, 88%) for fluency of speech, 4.3% (RRR, 84%) for swallowing, 6.0% (RRR, 53%) for lower-limb function, 9.3% (RRR, 75%) for upper-limb function, 7.4% (RRR, 60%) for shopping, and 10.5% (RRR, 50%) for visiting outside usual residence (P < .05, two-tailed, for all items). CONCLUSIONS--Carotid endarterectomy reduced the risk for impairment of function among patients with recent symptomatic cerebral ischemia and ipsilateral high-grade carotid stenosis.

15. Gasecki AP, Ferguson GG, Eliasziw M, Clagett GP, Fox AJ, Hachinski V, Barnett HJ: Early endarterectomy for severe carotid artery stenosis after a nondisabling stroke: results from the North American Symptomatic Carotid Endarterectomy Trial. J Vasc Surg 1994;20:288-295.
PURPOSE: The timing of carotid endarterectomy (CE) after a recent nondisabling stroke remains controversial. Delaying surgery in such cases may needlessly place patients at risk for a recurrent stroke that may be major and disabling. This study examines the prognostic implications of performing early endarterectomy compared with delayed endarterectomy in patients from the North American Symptomatic Carotid Endarterectomy Trial. METHOD: This retrospective, subgroup analysis involved 100 surgical patients with severe (70% to 99%) angiographically defined carotid artery stenosis, who were diagnosed with a nondisabling hemispheric stroke at entry into the trial. Forty-two CEs were performed within 30 days (early group, ranging 3 to 30 days), and 58 were performed beyond 30 days (delayed group, range 33 to 117 days) after stroke. The risk of subsequent stroke after CE was compared between the two groups. RESULTS: Baseline clinical characteristics were comparable in both the early and delayed groups. In the delayed group more lesions were identified ipsilateral to the symptomatic side on the preoperative computed tomography scans. The postoperative (30 days after endarterectomy) stroke rate was 4.8% in the early group and 5.2% in the delayed group, yielding a relative rate of 0.92 (95% confidence interval, 0.16 to 5.27; p = 1.00). No deaths occurred after operation in either group. At the end of 18 months, the rates of any stroke or death were 11.9% and 10.3% for the early and delayed groups, respectively, resulting in a relative rate of 1.15 (95% confidence interval, 0.38 to 3.52; p = 1.00). No association was found between an abnormal preoperative computed tomography scan result and the subsequent risk of stroke when early operation was used. CONCLUSION: Early CE for severe carotid artery stenosis after a nondisabling ischemic stroke can be performed with rates of morbidity and mortality comparable to those who receive delayed endarterectomy. Delaying the procedure by 30 days for patients with symptomatic high-grade stenosis exposes them to a risk of a recurrent stroke, which may be avoidable by earlier surgery.

16. Eliasziw M, Streifler JY, Fox AJ, Hachinski VC, Ferguson GG, Barnett HJ: Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial. Stroke 1994;25:304-308.
BACKGROUND AND PURPOSE: The importance of carotid plaque ulceration as a cause of cerebral ischemic symptoms remains uncertain. Moreover, its prominence in symptomatic patients with severe carotid stenosis is unknown. METHODS: The association between angiographically defined plaque ulceration and risk of subsequent stroke was assessed using Cox proportional hazards regression in 659 patients with severe (70% to 99%) carotid stenosis from the North American Symptomatic Carotid Endarterectomy Trial. RESULTS: Treatment assignment (medical versus surgical) and degree of ipsilateral stenosis were identified as having a significant influence on the results. The risk of ipsilateral stroke at 24 months for medically treated patients with ulcerated plaques increased incrementally from 26.3% to 73.2% as the degree of stenosis increased from 75% to 95%. For patients with no ulcer, the risk of stroke remained constant at 21.3% for all degrees of stenosis. The net result yielded relative risks of stroke (ulcer versus no ulcer) ranging from 1.24 (95% confidence interval, 0.61 to 2.52) to 3.43 (95% confidence interval, 1.49 to 7.88). Conversely, for surgically treated patients with antecedent presence of an ulcerated plaque, the risk of stroke increased slightly at the highest degrees of stenosis. Overall, carotid endarterectomy reduced the risk of ipsilateral stroke at 24 months by at least 50%. Similar results were obtained for risk of major ipsilateral stroke and risk of all strokes and death. CONCLUSIONS: The presence of angiographically defined ulceration for medically treated symptomatic patients is associated with an increased risk of stroke. The risk of stroke more than doubles at higher degrees of stenosis. Carotid endarterectomy is beneficial in substantially reducing the risk of stroke, regardless of plaque ulceration and degree of severe carotid stenosis.

17. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group. Lancet 1991;337:1235-1243.
The European Carotid Surgery Trial is a multicentre trial of carotid endarterectomy for patients who, after a carotid territory non-disabling ischaemic stroke, transient ischaemic attack, or retinal infarct, are found to have a stenotic lesion in the relevant (ipsilateral) carotid artery. Over the past 10 years 2518 patients have been randomised, and the mean follow-up is now almost 3 years among the 2200 thus far available for analysis of the incidence of strokes that lasted more than 7 days. For the patients with "moderate" (30-69%) stenosis on their prerandomisation angiogram the balance of surgical risk and eventual benefit remains uncertain, and full recruitment continues. For 374 patients with only "mild" (0-29%) stenosis there was little 3-year risk of ipsilateral ischaemic stroke, even in the absence of surgery, so any 3-year benefits of surgery were small, and were outweighed by its early risks. For 778 patients with "severe" (70-99%) stenosis, however, the risks of surgery were significantly outweighed by the later benefits: although 7.5% had a stroke (or died) within 30 days of surgery, during the next 3 years the risks of ipsilateral ischaemic stroke were (by life-table analysis) an extra 2.8% for surgery-allocated and 16.8% for control patients (a sixfold reduction, p less than 0.0001). There was also a small reduction in other strokes, and at 3 years the total risk of surgical death, surgical stroke, ipsilateral ischaemic stroke, or any other stroke was 12.3% for surgery and 21.9% for control (difference 9.6% SD 3.3, 2p less than 0.01). The main concern was to avoid disabling or fatal events, and, among severe stenosis patients, 3.7% had a disabling stroke (or died) within 30 days of surgery, an extra 1.1% surgery versus 8.4% control (p less than 0.0001) had a disabling or fatal ipsilateral ischaemic stroke by 3 years, and the total 3-year risk of any disabling or fatal stroke (or surgical death) was 6.0% surgery versus 11.0% control (overall difference 5.0% SD 2.3, 2p less than 0.05); but, for disabling or fatal stroke the control risks seemed to diminish after the first year, so delay of surgery by just a few months after clinical presentation might make this overall difference non-significant.

18. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators. N Engl J Med 1991;325:445-453.
BACKGROUND. Without strong evidence of benefit, the use of carotid endarterectomy for prophylaxis against stroke rose dramatically until the mid-1980s, then declined. Our investigation sought to determine whether carotid endarterectomy reduces the risk of stroke among patients with a recent adverse cerebrovascular event and ipsilateral carotid stenosis. METHODS. We conducted a randomized trial at 50 clinical centers throughout the United States and Canada, in patients in two predetermined strata based on the severity of carotid stenosis--30 to 69 percent and 70 to 99 percent. We report here the results in the 659 patients in the latter stratum, who had had a hemispheric or retinal transient ischemic attack or a nondisabling stroke within the 120 days before entry and had stenosis of 70 to 99 percent in the symptomatic carotid artery. All patients received optimal medical care, including antiplatelet therapy. Those assigned to surgical treatment underwent carotid endarterectomy performed by neurosurgeons or vascular surgeons. All patients were examined by neurologists 1, 3, 6, 9, and 12 months after entry and then every 4 months. End points were assessed by blinded, independent case review. No patient was lost to follow-up. RESULTS. Life-table estimates of the cumulative risk of any ipsilateral stroke at two years were 26 percent in the 331 medical patients and 9 percent in the 328 surgical patients--an absolute risk reduction (+/- SE) 17 +/- 3.5 percent (P less than 0.001). For a major or fatal ipsilateral stroke, the corresponding estimates were 13.1 percent and 2.5 percent--an absolute risk reduction of 10.6 +/- 2.6 percent (P less than 0.001). Carotid endarterectomy was still found to be beneficial when all strokes and deaths were included in the analysis (P less than 0.001). CONCLUSIONS. Carotid endarterectomy is highly beneficial to patients with recent hemispheric and retinal transient ischemic attacks or nondisabling strokes and ipsilateral high-grade stenosis (70 to 99 percent) of the internal carotid artery.