Babu, Maya A. MD*; Meissner, Irene MD‡; Meyer, Fredric B. MD*
Dr Francis Murphey reported the first successful carotid endarterectomy (CEA) at the American Academy of Neurologic Surgery in 1953. In 1954, Eastcott et al1 published their experience with surgical revascularization of the internal carotid artery in a patient with an impending stroke resulting from a thrombus. Over the last 30 years, there have been significant advances in the medical, surgical, and endovascular treatment of patients suffering from atherosclerotic carotid stenosis.2 Given the different treatment options, a number of randomized controlled trials have provided physicians with Class I evidence for optimal treatment for symptomatic and asymptomatic patients suffering from atherosclerotic stenosis of the internal carotid artery.3 For example, the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial1,4,5 demonstrate the efficacy of endarterectomy over medical therapy in reducing the risk of stroke. In these older studies, the incidence of perioperative stroke (within 30 days of surgery) or death was 5.8% and 6.7%, respectively, a risk that by today’s standards would be considered unacceptable given that multiple surgical studies that have demonstrated a perioperative morbidity and mortality of <3.0%.
Two large randomized trials have addressed the question of the relative safety of carotid artery stenting (CAS) compared with CEA in symptomatic and asymptomatic patients with >50% carotid artery stenosis by NASCET criteria. Specifically, in the International Carotid Stenting Study (ICSS), 1713 patients were initially randomized from 50 largely European academic centers.6 The interim analysis has recently been reported. The main safety end point—stroke, death, or procedural myocardial infarction at 120 days—was 8.5% and 5.2% for CAS and CEA, respectively (P = .006). The overall risk of stroke was higher in the stenting group than in the endarterectomy group, although at 30 days the incidence of disabling stroke was similar in both groups (1.7%). Concerns over this study included the limited experience of some interventionalists, the use of a variety of stents, and the incomplete use of embolic protection device (in only 72% of patients).
The second trial comparing outcomes in patients with symptomatic and asymptomatic internal carotid artery stenosis treated by CEA vs CAS is the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).7 The study enrolled 2502 patients at 117 centers in the United States and Canada. The primary end point for the study was any periprocedural stroke, myocardial infarction, death, or postprocedural ipsilateral stroke up to 4 years after intervention. There were rigorous training and credentialing for interventionalists8 and attempts to use single stenting and embolic protection devices. There was no significant difference in the rates of the primary end point between CAS and CEA (7.2% vs 6.8%; P = .51; hazard ratio = 1.11; 95% confidence interval, 0.81-1.511) at a mean follow-up of 2.5 years.7 Outcomes were slightly better with CAS for patients <70 years of age and with CEA for patients >70 years. In the overall study, the risk of stroke was less for CEA, but there was an increased incidence of myocardial infarction (CAS and CEA: stroke, 4.1% vs 2.3%, P = .01; myocardial infarction, 1.1% vs 2.3%, P = .03).9 The inclusion of asymptomatic cardiac ischemia as a primary end point in CREST has been criticized by a number of commentators.10 The clinical relevance of including silent cardiac events is questionable because results from the patient questionnaire (Short Form-36) in CREST demonstrated no adverse effects on quality of life resulting from these cardiac events. Without the inclusion of asymptomatic cardiac ischemia in CREST as a primary end point, CEA would have proved to be a safer procedure because of a higher incidence of perioperative strokes and death in the stenting group.2,3,11
In all trials, there was no evaluation of recurrent stenosis. The issue of durability of a procedure is important from several perspectives. First, there is a risk with any intervention, and accordingly, repeat procedure(s) by definition increase the overall lifetime patient risk for treatment of a specific disease. Second, repeat procedures increase healthcare expenses. Given the prevalence of carotid occlusive disease, the potential cost of repeat procedures is not insignificant. The purpose of the present study is to provide outcomes data on the perioperative risks and incidence of recurrent stenosis after CEA. We seek to present long-term follow-up results for a series with initial data published in 2003.
PATIENTS AND METHODS
Beginning in 1988, all patients undergoing CEA by a single surgeon were followed up prospectively, including a 3-month postoperative ultrasound and then annually thereafter through 2010 to provide a minimum of 1.5 years of follow-up. All patients were evaluated by a neurologist preoperatively, and any patient who experienced a postoperative decline or deficit was examined by a cerebrovascular neurologist. Definition of stroke in late follow-up included any permanent ischemic event in the carotid distribution that would include all types of stroke, including small-vessel lacunar-type infarctions that might not have been related to the prior carotid surgery. All patients were maintained on antiplatelet therapy with >90% of patients on aspirin 81 mg daily and the remainder on clopidogrel, a combination of clopidogrel and aspirin, or Coumadin necessitated by cardiac comorbidities. This study was approved by the Mayo Institutional Review Board, and informed consent for the study was not necessary.
The technique of CEA has been well described and includes intraoperative electroencephalographic monitoring, moderate induced hypertension during carotid cross-clamping, selective shunting, and repair of the arteriotomy with a patch graft, either a Hemashield Dacron collagen–impregnated graft (95%) or a saphenous vein graft (5%).12
Of the 1492 patients followed up over the time period of this study, 1335 underwent unilateral endarterectomies and 157 had bilateral endarterectomies performed at different time points. For the purposes of this study, the data from the 1335 patients are reported. Long-term follow-up neurologic and ultrasound data were available for 88% of patients. There were 427 women (32%) and 908 men (68%) with a median age of 70 years. A total of 802 patients (60%) were symptomatic, defined as having had a transient ischemic attack or prior stroke ipsilateral to the carotid occlusion.
There were 5 patients (0.4%) who suffered a 90-day perioperative stroke and 7 patients (0.5%) who died within 90 days as a result of cardiac problems (n = 3), cerebral hematoma (n = 3), or respiratory issues (n = 1). Five patients were brought back to surgery for exploration of a wound hematoma; these patients had no sequelae. Cranial nerve injury included hypoglossal nerve (n = 2), vagus nerve (n = 1), and 11th nerve (n = 1). All but 1 nerve injury resolved by 6 months. Six patients had mandibular nerve dysfunction. There was 1 wound infection requiring a washout. With regard to the data analysis, we classified all patients who suffered a stroke as having a major morbidity and classified cranial nerve dysfunctions as minor morbidities. In regard to the postoperative hematoma, a practice change was instituted in which intraoperative heparin administration was reduced from 5000 to 3000 U. Since that change, there have been no postoperative cervical or cerebral hematomas.
In regard to the primary purpose of this study, 5 patients (0.4%) had documented recurrent carotid stenosis >70% by NASCET criteria. In each of these patients, the ultrasound findings were confirmed by magnetic resonance angiography, computed tomographic angiography, or transfemoral cerebral angiography. Twelve patients (0.9%) had documentation of late stroke in the ipsilateral carotid distribution. The mean follow-up was 15.8 years.
The prevention of stroke remains a major public health concern.13 CEA has been the established treatment of choice for patients with symptomatic and asymptomatic internal carotid artery stenosis.10 Surgical results and risks of CEA have dramatically improved since the publication of the NASCET trial. Specifically, the expected total combined morbidity and mortality of open surgery by experienced surgeons is now significantly <3%, with the risk of recurrent stenosis after surgery reported to be as low as <0.5% in a large series.1,9-11,13 Recurrent stenosis for carotid endarterectomies has been documented in the literature to occur at varying rates. In 1 series of 1209 endarterectomies, the rate of recurrence was 6.8%; another study of 174 patients demonstrated recurrent stenosis rates of 9%. The amount of arterial stenosis that should lead to surgical treatment should exceed 50% (symptomatic patients) or 70% (asymptomatic patients).10
This study and other published contemporary series demonstrate that CEA has a very low perioperative risk and is an excellent intervention for hemodynamically significant carotid stenosis. These results also demonstrate excellent durability of surgery with a nominal long-term recurrent stenosis risk and stroke.14 In this report, with an average follow-up of 15.8 years, the risk of stroke referable to the repaired carotid artery was 0.9% and the recurrent stenosis rate was 0.4%. To the best of our knowledge, these are the longest follow-up data available on recurrent stenosis after endarterectomy. An article by Ballotta et al15 included a shorter patient follow-up period, and only a minority of endarterectomies were accompanied by patch grafts, whereas in our series, 100% of endarterectomies used a patch grafts.
A recently published analysis of the CREST trial demonstrated restenosis rates for endarterectomies at 2 years based on 70% stenosis at 6.3%. We believe our endarterectomy results are superior to previously published stenting results because we have shown a lower rate of restenosis (0.4% vs 6.3%), because our study includes an average follow-up of 15.8 years (not 2 years), and because our risks in terms of perioperative morbidity and mortality are quite low. Furthermore, the long-term risk of ipsilateral carotid distribution late stroke is extremely low after CEA (0.9%). It is our opinion that the results documented in this study reflect the use of meticulous intraoperative microsurgical and anesthesia technique, monitoring with selective shunting, and the use of a patch graft.
Carotid stenting has also undergone enormous changes in the last decade, with improvements in endovascular techniques and materials and a greater availability of more experienced and skilled interventionalists.10,11,13 In addition to technical improvements in both of these interventions, medical therapy has evolved to include new antiplatelet and hyperlipidemia therapies. It is reasonable to postulate that there will be further stroke reduction effects of these medical regimens that will need to be incorporated into the decision making regarding the best management of carotid stenosis for each individual patient.
Good indications for stenting at this time include recurrent carotid stenosis and vocal cord paresis. At this time, there is little published on the incidence of recurrent stenosis after stenting. However, a review of the literature indicates that the recurrent stenosis rate after stenting ranges from 7.5% to 12.5% with 2 years of follow-up data.1,2,15-17 The US Preventive Services Task Force estimated in 2007 that the prevalence of carotid stenosis was ≈1% nationwide.18 Given the risks and costs of stenting, the issue of recurrent stenosis requiring additional stenting procedures needs to be considered when advising patients on how best to manage their carotid occlusive disease.
CEA by the experienced surgeon remains the benchmark standard for the treatment of patients with carotid occlusive disease when considering the risk of stroke and long-term patency rates.12,15 The fact that surgery has superior durability with less risk of early and late stroke and recurrent stenosis suggests that it may be more beneficial in patients <70 years of age. Furthermore, it is possible that in the elderly patient the plaque is more friable and at risk for embolus, which may explain why data from the CREST trial and a large meta-analysis of pooled individual patient data from the Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis trial, the Stent-Protected Angioplasty Versus Carotid Endarterectomy trial, and the ICSS2,10 suggest lower risk in older patients with endarterectomy as opposed to stenting.
The limitations of this study include most prominently the use of a single surgeon’s experience at a single center; to make these findings more generalizable, a larger cross section of surgeons and institutions is warranted. Additionally, this is a case series, not a comparative study, of recurrent stenosis exploring the differences between CAS and CEA. This case series was intended to demonstrate a reasonable, achievable rate of morbidity, mortality, and durability for CEA to be used in counseling and discussing options with patients considering CEA vs CAS.
CEA is a safe, cost-effective, and durable treatment for carotid occlusive disease. In addition to procedural risk, the durability of the intervention needs to be considered when determining the optimum treatment for carotid occlusive disease.
The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.
We wish to thank Steven D. Thalacker, RN, for his assistance with compiling the data used in this study.
1. Eastcott HH, Pickering GW, Rob CG. Reconstruction of internal carotid artery in a patient with intermittent attacks of hemiplegia. Lancet. 1954;267(6846):994–996.
2. Adams HP Jr. Management of carotid artery stenosis: endarterectomy or stenting? Mayo Clin Proc. 2010;85(12):1071–1072.
3. Perkins WJ, Lanzino G, Brott TG. Carotid stenting vs endarterectomy: new results in perspective. Mayo Clin Proc. 2010;85(12):1101–1108.
4. Barnett HJ, Taylor DW, Eliasziw M, 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(20):1415–1425.
5. Rothwell PM, Gutnikov SA, Warlow CP. Reanalysis of the final results of the European Carotid Surgery Trial. Stroke. 2003;34(2):514–523.
6. Ederle J, Dobson J, Featherstone RL, et al.. Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial. Lancet. 2010;375(9719):985–997.
7. Mantese VA, Timaran CH, Chiu D, Begg RJ, Brott TG. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST): stenting versus carotid endarterectomy for carotid disease. Stroke. 2010;41(10 suppl):S31–S34.
8. Meyer FB. Sundt’s Occlusive Cerebrovascular Disease. 2nd ed. Philadelphia, PA: W.B. Saunders; 1994.
9. Hopkins LN, Roubin GS, Chakhtoura EY, et al.. The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase. J Stroke Cerebrovasc Dis. 2010;19(2):153–162.
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11. Davis SM, Donnan GA. Carotid-artery stenting in stroke prevention. N Engl J Med. 2010;363(1):80–82.
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18. Wolff T, Guirguis-Blake J, Miller T, Gillespie M, Harris R. Screening for Asymptomatic Carotid Artery Stenosis: Evidence Syntheses, No. 50. Rockville, MD: Agency for Healthcare Research and Quality; 2007. Report No. 08-05102-EF-1.
The authors present an extensive single-surgeon experience with carotid endarterectomy (CEA) for the purposes of evaluating the durability of treatment. Nearly 1500 patients are included with a mean follow-up of > 15 years. Results from this series are excellent, with fewer than one-half of a percent of patients having a periprocedural stroke, only 0.4% developing recurrent stenosis during the follow-up period, and a long-term ipsilateral stroke risk < 1%. Overall, the results are impressive and, to the best of our knowledge, represent the longest and largest series evaluating the durability of treatment after CEA. We congratulate the authors for this notable contribution to the literature on carotid occlusive disease and its treatments.
There are important limitations to mention. Given the significant experience of the senior author, the generalizability of these results to all CEAs is questionable. Furthermore, there is Class 1 evidence (Carotid Revascularization Endarterectomy Versus Stenting Trial [CREST]) supporting equally low major events after stenting and CEA. So, although these data are impressive and suggest excellent durability of treatment after CEA, their usefulness in an argument comparing the effectiveness of CEA and carotid stenting is questionable. We agree with the authors that the durability of treatment should be an important consideration when evaluating the risks and benefits of the treatments for carotid occlusive disease. Although there are limited long-term data addressing the restenosis risk after carotid angioplasty and stenting, the authors make a strong argument that CEA, when performed by an experienced surgeon, is a safe and highly durable treatment for carotid stenosis. However, long-term, multicenter, prospective data after carotid stenting and CEA are necessary before conclusive safety or cost-effectiveness comparisons can be performed.
Kyle M. Fargen
Brian L. Hoh
In the article entitled The Durability of Carotid Endarterectomy: Long Term Results for Restenosis and Stroke, Dr Meyer presents his perioperative complication rate, long term stroke risk, and recurrent stenosis rates after carotid endarterectomy (CEA) on both asymptomatic and symptomatic carotid stenosis in 1335 (1492 endarterectomies) consecutively treated patients dating back to 1988. All surgeries were performed under general anesthesia with selective shunting. All arteriotomies were closed with a patch angioplasty. Dr Meyer previously reported data on this same cohort with shorter follow-up.1 Ninety day perioperative stroke and death risk are recorded. Long-term follow-up (mean 15.8 years) was available for 88% of the cohort. Five patients (0.4%) developed recurrent stenosis over this time period. Ninety day combined major morbidity and death was 0.7%. Long term stroke risk was 1%. The authors conclude that carotid endarterectomy is a safe and durable treatment of carotid stenosis to which the results of carotid angioplasty and stenting (CAS) will need to be compared.
This is a very impressive series of carotid endarterectomies with outstanding results for restenosis, perioperative and long-term stroke. Caution: do not try this at home. These results were achieved by a master surgeon (by definition given the volume of surgeries, experience and outcomes) at a top-notch facility and do not necessarily reflect what a given surgeon can necessarily expect to offer their patients. While one message here is that terrific results can be achieved with endarterectomy, I believe there is a more important message. Namely that with some diligence, a given surgeon can accurately track his or her complications for a given procedure with very good long term longitudinal follow-up. This is very important as it gives that surgeon, and only that surgeon, the ability to accurately predict for a patient that he or she is offering this procedure what the likelihood of a given outcome or complication is. We should all learn from this and try to mimic this in our practices. This is particularly true for CEA because, unlike many neurosurgical procedures, there is very good data from trials suggesting that the benefit of surgery is only maintained if a certain complication rate can be achieved. I have become painfully aware that neither hospitals and their administrators, nor surgeons, nor patients have any idea of the complication rates of a given procedure by a given surgeon. Only by tracking our outcomes as Dr Meyer has can we honestly know whether or not we are achieving this complication rate benchmark in our own practices. If a surgeon is not meeting that benchmark, it suggests he or she undergo additional training or no longer offer that procedure.
Another point of this article is that, as the old saying goes, “there are many ways to skin a cat, but a good cat-skinner does it the same way each and every time.” I generally perform CEA for patients who do not meet the surgical high-risk criteria used in the SAPPHIRE trial.2 And CAS for those who do. With two exceptions. I consider old age to not be a high-risk feature and find that older patients do very well with CEA and often have tortuous and plaque-filled arches making CAS more dangerous. Secondly, I try to get a CTA on all patients that are potential candidates for CEA. If the lesion ends much higher than the body of C2 or if there does not appear to be either an anterior communicating artery or a posterior communicating artery on the side of the carotid in question, I proceed with CAS.
I find Dr Meyer's perioperative and long-term stroke risk to be a more important finding in this article than the recurrent stenosis rate. This is because it is very rare to have symptomatic restenosis and it remains very controversial in general when to revascularize a patient with restenosis after CEA.3 It bears mentioning that while I assume the results presented here are accurate, it is well known and scientifically demonstrated that surgeons who evaluate and report on their own results have a natural bias.4 It would be worthwhile to have an independent neurologist perform the analysis and publication. But finding such a neurologist willing to do this and a surgeon willing to subject his patients to this scrutiny might be difficult.
While I do believe this is the longest follow-up for restenosis for either CEA or CAS, bear in mind that this paper provides no data regarding the comparative value of the two. And while the long-term data is interesting, I suspect that any carotid that does not restenose within a couple of years would be much less likely to do so in longer follow-up and this notion is supported by the CAVATAS study.5 That said, there is adequate evidence that CAS patients do have increased restenosis rates compared to CEA.5 I suspect the low incidence in Dr Meyer's series is related to his use of patch angioplasty in all cases. A trial comparing CEA with and without patch angioplasty looking at restenosis and recurrent stroke would be of interest. Again, the real issue is how often restenoses lead to symptoms and or the need for additional procedures and how dangerous are those procedures?
Having performed both CAS and CEA at seven different hospitals, large and small, in the last few years, it has been my experience that one is much more likely to find an experienced team in any given hospital to perform CEA than CAS. This relates in part to the historical development of trials supporting the utility of CEA, ubiquitousness of carotid stenosis leading to the development of skilled and experienced carotid endarterectomy surgeons at most hospitals and lack of trained interventionalists with proper equipment at many hospitals. I have found CAS to be a technically challenging and risky procedure in certain individuals, even more so than aneurysm coiling or AVM embolization at times. Ultimately, however, a given patient's true complication risk from a CEA or CAS is defined by the individual surgeons/interventionalists that he/she has happened upon when in need of one of these highly technical and operator-dependent procedures. Because the risk/benefit margin is so small for carotid revascularization and the differences in complication rates between operators probably not insignificant and most often unknown, weather someone is revascularized with a CEA or CAS is likely less important than who is performing the procedure. But if we do not track and record outcomes from our patients we’ll never know.
Lake Success, Long Island, New York
1. Ecker RD, Pichelmann MA, Meissner I, et al.. Durability of carotid endarterectomy. Stroke 2003;34(12):2941–2944. View Full Text | PubMed | CrossRef Cited Here... |
2. Yadav JS, Wholey MH, Kuntz RE, et al.. Protected carotid-artery stenting versus endarterectomy in high-risk patients. N Engl J Med 2004;351(15):1493–1501. View Full Text | PubMed | CrossRef Cited Here... |
3. Lattimer CR, Burnand KG. Recurrent carotid stenosis after carotid endarterectomy. Br J Surg 1997;84(9):1206–1219. View Full Text | PubMed | CrossRef Cited Here... |
4. Rothwell P, Warlow C. Is self-audit reliable? Lancet 1995;346(8990):1623. Cited Here...
5. Bonati LH, Ederle J, McCabe DJ, et al.. Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial. Lancet Neurol 2009;8(10):908–917. PubMed | CrossRef Cited Here... |
1. What is the rate of recurrent stenosis in extracranial carotid atherosclerotic disease (of at least 70%) treated with carotid artery stenting (CAS)?
2. What is the reported rate of recurrent carotid stenosis following carotid endarterectomy (CEA) in modern studies?
3. Following stenting for intracranial atheromatous disease, what is the rate of in-stent stenosis?