The appropriate use of carotid endarterectomy

Abstract

For the first 30 years after carotid endarterectomy was first developed, anecdotal evidence was used to identify patients with internal carotid artery disease for whom this procedure would be appropriate. More recently, the appropriateness of carotid endarterectomy for symptomatic patients and asymptomatic subjects has emerged from 7 randomized trials. Risk of stroke and benefit from the procedure are greatest for symptomatic patients with at least 70% stenosis of the internal carotid artery. Within this group, carotid endarterectomy is most beneficial for the following patients: otherwise healthy elderly patients, those with hemispheric transient ischemic attack, those with tandem extracranial and intracranial lesions and those without evidence of collateral vessels. Risk of perioperative stroke and death is higher in the following groups, although they still benefit: patients with widespread leukoaraiosis, those with occlusion of the contralateral internal carotid artery and those with intraluminal thrombus. Patients with 50% to 69% stenosis experience lesser benefit, and some other groups may even be harmed by carotid endarterectomy, including women and patients with transient monocular blindness only. The procedure is indicated for patients presenting with lacunar stroke and for those with a nearly occluded internal carotid artery, but the benefit is muted. Patients with less than 50% stenosis do not benefit. In the largest randomized trial of asymptomatic subjects, the perioperative risk of stroke and death was very low (1.5%), but the results indicated that a prohibitively high number of subjects (83) must be treated to prevent one stroke in 2 years. The subsequent literature reported higher perioperative risks (2.8% to 5.6%). In asymptomatic individuals nearly half of the strokes that occur may be due to heart and small-vessel disease. These limitations counter any potential benefit. Another trial is in progress and may identify subgroups of asymptomatic subjects who would benefit. Meanwhile, most individuals without symptoms fare better with medical care.

Fig. 1: Kaplan–Meier curves for event-free survival with and without carotid endarterectomy. The curves show the probability of avoiding an ipsilateral stroke of any degree of severity (left-hand panels) and a disabling or fatal ipsilateral stroke (right-hand panels) among patients with carotid stenosis of at least 70% (top panels) or 50% to 69% (bottom panels) who were randomly assigned to undergo carotid endarterectomy (surgical group) or to receive medical therapy alone (medical group). Also shown are the p values from the Mantel–Haenstzel χ² test used to compare the survival curves, with the 95% confidence interval for each curve and the overlap between the confidence intervals indicated by bands of color. The numbers along the horizontal axis are the numbers of patients in each group who were still at risk during each year of follow-up. Reproduced with permission from Barnett HJM, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, et al, for the North American Symptomatic Carotid Endarterectomy Trial Collaborators. Benefit of carotid endarterectomy in symptomatic patients with moderate and severe stenosis. N Engl J Med 1998;339:1415-25. Copyright © 1998 Massachusetts Medical Society. All rights reserved.

Fig. 2: Kaplan–Meier 3-year risk of ipsilateral stroke in patients with at least 50% stenosis and transient monocular blindness (TMB) or hemispheric transient ischemic attack (HTIA). The difference in risk between medical and surgical therapy for patients presenting with hemispheric events is impressive (20.3% v. 10.8%), but for patients presenting with retinal events it is only modest (10.0% v. 8.7%). The number of patients were as follows: 142 with TMB treated medically, 215 with HTIA treated medically, 142 with TMB treated surgically and 197 with HTIA treated surgically. Reproduced, with permission, from Benavente O, Eliasziw M, Streifler JY, Fox AJ, Barnett HJM, Meldrum H, for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) Collaborators. Prognosis after transient monocular blindness associated with carotid artery stenosis. N Engl J Med 2001;345:1084-90. Copyright © 2001 Massachusetts Medical Society. All rights reserved.

Fig. 3: Cumulative hazard curves showing risk (hazard rate) of ipsilateral stroke for medically and surgically treated patients with either an occluded contralateral carotid artery or a stenosed but patent contralateral carotid artery. When the artery contralateral to the symptomatic side is occluded, patients treated medically (O-M = Occluded Medical) face a formidable risk at 2 years (69.4%). When the contralateral artery is stenosed but not occluded the risk with medical treatment is considerably lower (S-M = Stenosed Medical). Despite a high perioperative risk, patients undergoing surgical treatment in the presence of contralateral occlusion (O-S = Occluded Surgical) still benefit, as do patients with contralateral stenosis short of occlusion (S-S = Stenosed Surgical). Reproduced, with permission, from Gasecki AP, Eliasziw M, Ferguson GG, Hachinski V, Barnett HJM, for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET. J Neurosurg 1995;83:778-82.

Fig. 4: Thirty-day rate of perioperative stroke or death in surgically treated patients with contralateral occlusion and those with only contralateral stenosis. Data are for patients with either asymptomatic or symptomatic stenosis in the ASA and Carotid Endarterectomy (ACE) trial⁶ and symptomatic patients in the North American Symptomatic Carotid Endarterectomy Trial (NASCET).³ The high risk (12.3%) for asymptomatic patients with contralateral occlusion would recommend strongly against carotid endarterectomy for patients with this combination of lesions. The numbers of patients were as follows: asymptomatic patients in ACE trial, 1358 with stenosed and 154 with occluded contralateral artery; symptomatic patients in ACE trial, 1210 with stenosed and 82 with occluded contralateral artery; symptomatic patients in NASCET, 1354 with stenosed and 61 with occluded contralateral artery. Reproduced, with permission, from Inzitari D, Eliasziw M, Gates P, Sharpe BL, Chan RKT, Meldrum HE, et al, for the North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group. The causes and risk of stroke in subjects with an asymptomatic internal carotid artery. N Engl J Med 2000;342:1693-700. Copyright © 2000 Massachusetts Medical Society. All rights reserved.

Fig. 5: Five-year Kaplan–Meier curves of event-free survival (no ipsilateral stroke or perioperative stroke or death) for the Asymptomatic Carotid Atherosclerosis Study (ACAS) indicate a 5.9% difference in projected risk, favouring endarterectomy, at 5 years. However, between years 4 and 5 a series of strokes of unknown cause occurred in the medical treatment arm. The numbers of patients available for analysis at each year of follow-up appear along the horizontal axis (top and bottom numbers at each time point represent ACAS patients who underwent surgical and medical treatment respectively). At year 5 these numbers were very small. Superimposed on the graph (adapted from Barnett and collegues52) is the projected outcome for 1214 asymptomatic subjects in the ASA and Carotid Endarterectomy (ACE) trial, based on the 30-day perioperative rate of stroke or death (4.4%) extrapolated to 5 years. For this group the projected risk at 5 years is 7.2%, so the difference between this group and ACAS patients treated medically would be 3.8% — only 0.8% benefit per year. Clearly no benefit was present for the first 4 years of follow-up in the ACE subjects.