Timing of Carotid Endarterectomy for Patients With Symptomatic High-Grade Stenosis
Timing of Carotid Endarterectomy for Patients With Symptomatic High-Grade Stenosis
How soon should carotid endarterectomy be performed after ischemic stroke or transient ischemic attack (TIA) in patients with high-grade stenosis?
When a patient presents with an ischemic stroke or TIA, it is important to understand the underlying vascular anatomy of the lesion that produced the current symptoms. In some cases, such patients are found to have a high-grade (70% or more) stenosis that is ipsilateral to the side of the brain affected by the recent event. Many such patients may be candidates for carotid endarterectomy (CEA) if they are healthy enough to undergo the surgery and the surgeon has a low perioperative complication rate.
A review and meta-analysis of the large randomized clinical trials that showed benefit for CEA for high-grade ipsilateral stenosis found that certain subgroups tended to show more or less benefit from CEA. These trials include the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Combined, these trials have almost 5900 patients. When the benefits of CEA in terms of timing were analyzed, there was a clear trend for patients who had CEA within 2 weeks of last symptoms (either a TIA or stroke) to show more benefit than for patients who had a CEA later. But it is important to note that even patients who had the operation within 12 weeks of last symptoms also showed benefit, although the degree of benefit fell as the time between last symptoms and CEA progressed from less than 2 weeks to 12 weeks. Patients who had a CEA beyond 12 weeks after the last symptoms did not show any benefits.
When examined in absolute terms, the 5-year cumulative rate of ipsilateral ischemic stroke and any stroke or death within 30 days of CEA was reduced by 18.5% (vs medical therapy) in those who had the operation within 2 weeks, 9.8% if the operation occurred within 2-4 weeks, 5.5% if within 4-12 weeks, and only 0.8% at greater than 12 weeks. So there is still substantial benefit with delayed surgery up to 12 weeks, although the efficacy is much greater with early CEA. The degree of benefit with early CEA was greater in patients with 70%-99% stenosis compared with those with 50%-69% stenosis.
These results are based on subgroup analyses, and any type of subgroup findings are certainly open to ascertainment biases and are often not confirmed on subsequent studies. Nonetheless, some of these subgroups were in fact prespecified, which might reduce overt biases. On the other hand, an analysis of the confidence intervals shows that for most of the time epochs, there is much overlap, which means that any differences are likely not statistically significant. Also, patients with large strokes were typically excluded from the CEA studies, and most would not be candidates for early CEA in any case.
My conclusions from these data are that, if possible, early CEA after a stroke or TIA is preferable, especially in patients with 70%-99% ipsilateral stenosis. Waiting a few weeks is reasonable if there are complicating medical factors that might increase the risk of early CEA. Delays greater then 3 months appear to negate the benefits of CEA in this patient population.
Question
How soon should carotid endarterectomy be performed after ischemic stroke or transient ischemic attack (TIA) in patients with high-grade stenosis?
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Response from Mark Alberts, MD Professor of Neurology, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Director, Stroke Program, Northwestern Memorial Hospital, Chicago, Illinois |
When a patient presents with an ischemic stroke or TIA, it is important to understand the underlying vascular anatomy of the lesion that produced the current symptoms. In some cases, such patients are found to have a high-grade (70% or more) stenosis that is ipsilateral to the side of the brain affected by the recent event. Many such patients may be candidates for carotid endarterectomy (CEA) if they are healthy enough to undergo the surgery and the surgeon has a low perioperative complication rate.
A review and meta-analysis of the large randomized clinical trials that showed benefit for CEA for high-grade ipsilateral stenosis found that certain subgroups tended to show more or less benefit from CEA. These trials include the European Carotid Surgery Trial (ECST) and the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Combined, these trials have almost 5900 patients. When the benefits of CEA in terms of timing were analyzed, there was a clear trend for patients who had CEA within 2 weeks of last symptoms (either a TIA or stroke) to show more benefit than for patients who had a CEA later. But it is important to note that even patients who had the operation within 12 weeks of last symptoms also showed benefit, although the degree of benefit fell as the time between last symptoms and CEA progressed from less than 2 weeks to 12 weeks. Patients who had a CEA beyond 12 weeks after the last symptoms did not show any benefits.
When examined in absolute terms, the 5-year cumulative rate of ipsilateral ischemic stroke and any stroke or death within 30 days of CEA was reduced by 18.5% (vs medical therapy) in those who had the operation within 2 weeks, 9.8% if the operation occurred within 2-4 weeks, 5.5% if within 4-12 weeks, and only 0.8% at greater than 12 weeks. So there is still substantial benefit with delayed surgery up to 12 weeks, although the efficacy is much greater with early CEA. The degree of benefit with early CEA was greater in patients with 70%-99% stenosis compared with those with 50%-69% stenosis.
These results are based on subgroup analyses, and any type of subgroup findings are certainly open to ascertainment biases and are often not confirmed on subsequent studies. Nonetheless, some of these subgroups were in fact prespecified, which might reduce overt biases. On the other hand, an analysis of the confidence intervals shows that for most of the time epochs, there is much overlap, which means that any differences are likely not statistically significant. Also, patients with large strokes were typically excluded from the CEA studies, and most would not be candidates for early CEA in any case.
My conclusions from these data are that, if possible, early CEA after a stroke or TIA is preferable, especially in patients with 70%-99% ipsilateral stenosis. Waiting a few weeks is reasonable if there are complicating medical factors that might increase the risk of early CEA. Delays greater then 3 months appear to negate the benefits of CEA in this patient population.