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EJMINT Original Article, 2013: 1346000132 (15th November 2013)

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Our Single-Centre Experience of Carotid Artery Stenting in High-Risk Patients over a 10-year period
Joanna P Ti, David Carmody, Sarah Power, et al
EJMINT Original Article, 2013: 1346000132 (15th November 2013)

Our Single-Centre Experience of Carotid Artery Stenting in High-Risk Patients over a 10-year period

EJMINT Original Article, 2013: 1346000132 (15th November 2013)
Joanna P Ti, David Carmody, Sarah Power, Alison Corr, Joan Moroney, David Williams, Seamus Looby, Alan O'Hare, John Thornton, Paul Brennan

Abstract

INTRODUCTION: Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are means of carotid revascularisation in patients with carotid artery stenosis. Recent large randomised control trials (RCTs) have compared these two methods of carotid revascularisation, with conflicting results. We review the outcomes of all patients who have undergone CAS at a single centre. We also contrast the clinical features and outcomes of patients with symptomatic versus asymptomatic carotid artery disease. METHODS: We maintained a database of all patients undergoing CAS over a 10-year period. Patient demographic information was collected, as well as intra-procedural details, complications occurring within 30 days of the procedure and clinical follow-up. RESULTS: 203 patients underwent CAS over 10 years. After exclusions, 199 patients (M:F, 134:65) were included. Our patient population consisted largely of those unsuitable for surgery and therefore comprised a higher-risk group when compared to the patient population in the RCTs. There were more symptomatic patients (n=123, 61.8%) than asymptomatic patients (n=76, 38.2%). The 30-day major adverse event (MAE) rate was 8.5 % (n=17), including stroke (n=6, 3.2 %), myocardial infarction (MI) (n=2, 1.0 %) and death (n=9, 4.5 %). There was no statistical difference between MAEs in the symptomatic (n=11, 8.9 %) compared to the asymptomatic group (n=6, 7.9 %). CONCLUSIONS: The outcomes of CAS performed at our centre in an unrestricted high-risk group of patients compare favourably with those of recent RCTs. Despite a higher incidence of ischaemic heart disease (IHD) in patients with asymptomatic disease, outcomes were similar to those of symptomatic patients. Our data suggests that CAS is a safe and dependable method of carotid revascularisation when offered as an alternative to CEA or if patients are unsuitable for CEA.

Abbreviations

AAA
abdominal aortic aneurysm
CABG
coronary artery bypass graft
CAS
carotid artery stenting
CEA
carotid endarterectomy
CTA
computed tomography angiography
CVA
cerebrovascular accident
IHD
ischaemic heart disease
MAE
major adverse event
MI
myocardial infarct
PVD
peripheral vascular disease
RCT
randomised controlled trial
TIA
transient ischaemic attack

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Introduction

Carotid artery atherosclerosis and stenosis is a major risk factor for ischaemic stroke [1]1. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’ Fallon WM, Wiebers DO; Ischaemic stroke subtypes: a population-based study of incidence and risk factors; Stroke 1999;30:2513-6. Carotid endarterectomy (CEA) has been shown to decrease the risk of recurrent stroke. [2-4]2. Mayberg MR, Wilson SE, Yatsu F, Weiss DG, Messina L, Hershey LA, Colling C, Eskridge J, Deykin D, Winn HR, Veterans Affairs Cooperative Studies Program 309 Trialist Group; Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis; JAMA. 1991;266:3289-3294 [PubMed] [Full Text Sources]3. North American Symptomatic Carotid Endarterectomy Trial Collaboration; Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis; N Engl J Med. 1991;325:445-4534. European Carotid Surgery Trialists Collaborative Group; MCR European carotid surgery trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis; Lancet 1991;337:1235-1243. Carotid artery stenting (CAS) has been demonstrated to be an alternative method of carotid revascularisation [5]5. Yadav JS, Wholey MH, Kuntz RE et al.; Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy Investigators. Protected Carotid-Artery Stenting versus Endarterectomy in High-Risk Patients; N Engl J Med. 2004;351:1493-501 [PubMed] [Full Text Sources]. Recent large randomised control trials (CREST, ICSS) [6-7]6. Brott TG, Hobson RW, Howard G, et al., the CREST investigators; Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis; N Engl J Med 2010;363:11-23 [PubMed] [Full Text Sources]7. Ederle J, Dobson J, Featherstone RL, Bonati LH, van der Worp HB, et al., for the International Carotid Stenting Study investigators; 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;375:985-97 [PubMed] [Full Text Sources] have compared the two methods of carotid revascularisation, with equivalent results in CREST and CEA appearing superior in the interim ICSS study (see Table 1 for summary of recent CAS/CEA trials). Trials prior to CREST such as CAVATAS [8]8. The CAVATAS investigators; Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial; The Lancet 2001;357:1729-1737 resulted in a 30-day rate of stroke of 10.0 % in the CAS group and 9.9 % in the CEA group. In the EVA-3S [9]9. Mas JL, Chatellier G, Beyssen B, et al., the EVA-3S Investigators; Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis; N Engl J Med. 2006;355:1660-71 [PubMed] [Full Text Sources] trial, the 30-day stroke/death rate was 9.6 % for CAS and 3.9 % for CEA.

Table 1 Summary of recent CAS/CEA trials

Given that patients are selected for RCTs based on strict inclusion and exclusion criteria, these patients may not reflect the patient population seen and treated in many centres. At our centre, for example, we randomised only 4 patients into the ICSS RCT, as the majority of patients undergoing carotid revascularisation during that time were unsuitable for randomisation. Exclusion criteria for the ICSS trial include previous major severe stroke, previous carotid endarterectomy or stenting in the randomised artery and perhaps most notable from a day-to-day clinical point of view, contraindications for either treatment as well as planned coronary artery bypass grafting or other major surgery. Exclusion criteria in CREST include severe previous stroke, chronic atrial fibrillation in the proceeding 6 months or requiring anticoagulation or myocardial infarction in the previous 30 days or unstable angina.

In this retrospective review we aim to:

  1. Assess the outcomes of all patients who have undergone CAS at one centre
  2. Identify differences between patients with symptomatic versus asymptomatic carotid artery disease

These data in an unrestricted patient population should reflect normal daily practice in many centres compared to patients chosen for RCTs.

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Patients and Methods

Patients and data collection

All patients who underwent CAS at our institution from December 2001 to June 2011 were included in the database. Data was collected prospectively at the time of carotid stenting and entered into the database. Prospective data collection included patient age, sex, clinical presentation and examination, risk factors and history of previous CAS or CEA. Retrospective data collection included discharge summaries, reports of non-invasive imaging and stenting procedure, clinic letters from follow-up and chart reviews.

Symptoms and risk factors

In accordance with the recent CREST inclusion criteria, patients who underwent CAS were classified as symptomatic if they had experienced neurological symptoms attributed to the study carotid artery within the preceding 6 months. Symptomatic patients included those who had experienced a cerebral infarct, transient ischaemic attack (TIA) or amaurosis fugax in relation to the study carotid artery.

Asymptomatic patients included those who had neurological symptoms attributed to the non-study carotid artery, coronary artery bypass graft (CABG) work-up and TIA/stroke due to study carotid artery stenosis but not in the preceding 6 months. Patients who experienced a presyncopal or syncopal event were also considered asymptomatic. Elective patients were considered asymptomatic, where carotid artery stenosis was an incidental finding on non-invasive imaging.

Data was also collected on the risk factor profile of the patients who underwent CAS. The following risk factors were recorded: hypertension, hyperlipidemia, diabetes mellitus, previous stroke, known or pre-existing carotid artery stenosis or occlusion, previous CAS, previous CEA, history of smoking, obesity, ischaemic heart disease (IHD) and finally, peripheral vascular disease (PVD)/abdominal aortic aneurysm (AAA) were grouped together as one vascular risk factor.

Non invasive imaging

All patients underwent either carotid Doppler ultrasound, magnetic resonance angiography (MRA) of the carotid arteries or computed tomography angiography (CTA) of the carotid arteries. Data was collected for both right and left carotid arteries, regardless of which carotid artery was stented. The degree of stenosis was grouped into ranges using velocity criteria in Doppler ultrasound and using the NASCET criteria [3]3. North American Symptomatic Carotid Endarterectomy Trial Collaboration; Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis; N Engl J Med. 1991;325:445-453 in CTA/MRA. The categories were: < 50 % stenosis, 50 % to 69 % stenosis, 70 % to 99 % stenosis, 100 % stenosis or occluded and finally, if there was already a stent in-situ from previous CAS.

Carotid artery stenting procedure

All the carotid stenting procedures were carried out by one or both of two experienced interventional neuroradiologists. Patients were preloaded with antiplatelet medication, consisting of a combination of aspirin 325 mg and clopidogrel 75 mg for at least 3 days prior to the procedure. Systemic heparinisation was achieved with heparin bolus varying from 5,000 IU for patients weighing 50 kg and less and 7,000 IU for patients weighing more than 50 kg. Until recently, patients were also placed on a heparin infusion for 24 h post procedure; however, we have recently discontinued this practice following 2 consecutive complications of reperfusion haemorrhage post-stenting.

Degree of stenosis was assessed angiographically pre stenting using the NASCET criteria [3]3. North American Symptomatic Carotid Endarterectomy Trial Collaboration; Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis; N Engl J Med. 1991;325:445-453, using the categories as in the non-invasive imaging. Only one carotid artery (right or left) was stented per procedure.

Vascular access was achieved via an 8Fr sheath in the common femoral artery. Then an 8Fr Mach 1 MPD guide catheter (Boston Scientific, Massachusetts, USA) was placed into the common carotid artery followed by deployment of the Emboshield Embolic Protection System (Abbott Vascular, Illinois, USA) into the internal carotid artery distal to the stenosis, where anatomically suitable. One of four carotid stents were used: Precise (Cordis, New Jersey, USA), Xact (Abbott Vascular, Illinois, USA), SMART (Cordis, New Jersey, USA) or Acculink (Abbott Vascular, Illinois, USA). Post-stenting balloon angioplasty was performed routinely with a 6 x 40 mm Viatrac balloon (Abbott Vascular, Illinois, USA) in all patients, while pre-stenting balloon angioplasty with a 4 x 40 mmg Viatrac balloon was performed at the discretion of the operator. Arteriotomy closure was performed with either the Perclose (Abbott Vascular, Illinois, USA) or Angio-Seal (St Jude Medical, Minnesota, USA) devices.

Procedural and peri-procedural complications

Inability to deploy a stent was considered a failed procedure. The peri-procedural period was deemed to be 30 days from date of stenting. All immediate and delayed complications were recorded. This included vasospasm (asymptomatic), bradycardia requiring atropine or pacemaker insertion, hypotension requiring fluids, transient dysphasia or weakness (lasting < 24 h), stroke, myocardial infarction (defined as 2 out of 3 criteria of typical chest pain, raised cardiac enzymes and/or electrocardiogram changes), groin haematoma or pseudoaneurysm requiring/not requiring transfusion/surgery and death from any cause within 30 days. Stroke was defined as neurological deficit lasting more than 24 hours (CREST).

Clinical follow-up

In the immediate post-procedural period, patients were admitted to a high-dependency unit, with close control of blood pressure, intravenous fluids, bed rest and hourly neurological examinations. All patients were assessed following return to the ward and the following day by a stroke physician, who could be a stroke neurologist or a geriatrician specialising in stroke. Clinic follow up by the referring physician was performed 6 weeks and 6 months after carotid artery stenting. Carotid Doppler US was also performed.

Statistical analysis

Data was analysed using Graphpad Prism 6 (GraphPad Software Inc, California, USA). Comparison between groups was analysed using Student t-test, Chi-square test or Fisher’s Exact test as appropriate. Statistical significance was considered at p<0.05.

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Results

Patient demographics, symptoms and risk factors (Table 2)

Table 2 Patient demographics, symptoms and risk factors

203 patients underwent carotid artery stenting over a 9 ½ year time period between December 2001 and May 2011, averaging 21.4 procedures per year. After excluding 4 patients who underwent CAS as part of acute stroke treatment, 199 patients were available for data analysis. There were 134 (67.3 %) male patients and 65 (32.7 %) female patients who underwent CAS. The average age of the patients was 70.1 years; the youngest patient was male, 40 years of age, and the oldest patient was female, 89 years of age. The average age of both the symptomatic (69.8 years) and asymptomatic groups (70.4 years) were similar.

Based on the CREST inclusion criteria, stating that ‘patients were considered to be symptomatic if they had a transient ischaemic attack, amaurosis fugax, or minor nondisabling stroke involving the study carotid artery within 180 days before’, there were more symptomatic (n=123, 61.8 %) patients than asymptomatic patients (n=76, 38.2 %). The largest group of patients presented with infarct resulting in hemiparesis/dysphasia attributed to the study carotid artery (n=65, 32.7 %). The second largest category within the symptomatic group were patients who experienced a TIA attributed to the study carotid artery within the preceding 6 months (n=43, 21.6 %). Other patients considered symptomatic based on the CREST patient selection included patients presenting with amaurosis fugax (n=15, 7.5 %).

Amongst the 76 asymptomatic patients (38.2 %), there were 40 elective (20.1 %) patients, 10 patients with presyncopal event (5.0 %), 6 patients with neurological symptoms due to contralateral carotid artery disease (3.0 %), 5 patients who presented as part of CABG work up (2.5 %) and 6 others (3.0 %). In addition, based on the CREST patient selection, patients who had a stroke/TIA due to the study carotid artery but not within the last 6 months (n=9, 4.5 %) were all considered asymptomatic. It is worth noting that the last asymptomatic patient was stented in December 2009. All patients stented in the final year and a half of the study presented with symptoms (n=29, 14.6 %).

Risk factors of hypertension, diabetes, previous CVA/TIA, previous CEA or history of smoking or obesity did not differ between the symptomatic and asymptomatic patients. The most prevalent risk factor was hypertension (n=98, 49.3 %), which was seen in both symptomatic (n=57, 46.3 %) and asymptomatic (n=41, 53.9 %) patients. Asymptomatic patients were more likely to have the following risk factors: previous carotid artery stenting (p<0.01), known pre-existing carotid stenosis/occlusion (p<0.01) and IHD (p<0.01).

Carotid artery stenosis and stenting and peri-procedural complications (Table 3)

Table 3 summarises the degree of stenosis, success of the procedure and peri-procedural complications.

Table 3 Carotid stenting procedure and peri-procedural complications

The majority of patients undergoing carotid artery stenting had 70 %-99 % carotid artery stenosis on angiography (n=189, 95.0 %), with no significant difference in degree of stenosis between symptomatic or asymptomatic patients. No patients had less than 50 % stenosis on angiography. Two patients undergoing CAS had an occluded carotid artery on angiography. One of these patients presented with right hemispheric TIAs and MRA demonstrated 99 % stenosis of the left carotid artery and occlusion of the right carotid artery; this was confirmed at angiography where attempted stenting of the right carotid artery unsuccessful. The second of these 2 patients presented with hemiparesis and while non-invasive imaging demonstrated a 99% stenosis of the study carotid artery, findings at angiography and stenting were of an occluded carotid artery, which refills from collaterals; this was successfully stented.

The majority of the procedures were successful (n=188, 94.5 %), with failed deployment of carotid stent in 11 patients (5.5 %). These were due to tortuosity of vessels with failure to either place the guide in the carotid artery or failure to advance/deploy the stent due to vessel tortuosity and one case resulted from failure to open up an occluded carotid artery. The most recent failed stenting procedure was in April 2009; this was the only procedure abandoned due to the tortuosity of the iliac arteries.  Since then, all stenting procedures have been successful (n=43, 21.6 %). No significant difference was noted between symptomatic and asymptomatic patients in terms of success of the stenting procedure.

There were no complications in the 30-day peri-procedural period in 141 patients (70.9 %). Major adverse event (MAE) of death, stroke and myocardial infarct occurred in 17 patients (8.5 %) with similar frequency in both symptomatic (n=11, 8.9 %) and asymptomatic patients (n=6, 7.9 %).

Table 4 Summary of patient characteristics of the patients who experienced a major adverse event

Table 4 lists the patients who experienced a MAE within the peri-procedural period. Death within 30 days occurred in 9 patients (4.6%): 3 from cardiac causes and 6 from strokes. Of the 6 strokes, 3 were from reperfusion hemorrhages (intracranial hemorrhage in territory of stented carotid artery), 2 from hemorrhagic infarcts following tissue plasminogen activator (tPA) administration due to thrombotic complications and 1 from an ischaemic stroke due to stent thrombosis. Seven deaths occurred in symptomatic patients (5.7 %) while 2 occurred in asymptomatic patients (2.6 %) but this was also not statistically significant. Of the 2 asymptomatic patients, one was an 83 year-old female patient who was referred as part of CABG workup and the other was a 70 year-old female patient who experienced a presyncopal event in the setting of known contralateral carotid occlusion and previous CEA of the carotid artery for stenting. There were 6 patients (3.0 %) who experienced a stroke in the peri-procedural period and 2 patients (1.0 %) who experienced an MI. Although these complications are considered MAEs, 3 patients with a peri-procedural stroke had full neurological recovered by 1 week. Two further patients with a peri-procedural stroke had regained mobility and one of the 2 patients with a peri-procedural MI was clinically well when reviewed at their earliest clinic follow-up. Overall, of the 8 patients who experienced a stroke or myocardial infarct, 7 had a modified Rankin score (mRS) [12,13]12. Rankin J; Cerebral vascular accidents in patients over the age of 60. II. Prognosis; Scott Med J. 1957;2(5):200-15 [PubMed]13. Farrell B, Godwin J, Richards S, et al.; The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results; J Neurol Neurosurg Psychiatry 1991;54(12):1044-54 [PubMed] [Full Text Sources] of 2 or less by clinic follow-up.

Non-MAE complications included groin site complications (n=19, 9.5 %) including haematoma and pseudoaneurysm. Whilst most of the groin site complications were managed conservatively (n=16, 8.0 %), 2 patients required further management in the form of blood transfusion and 1 patient developed a pseudoaneurysm following deployment of Angio-Seal closure device, which necessitated surgical repair. A total of 10 patients (5.0 %) experienced a TIA, that is, a brief neurological deficit lasting less than 24 h with full recovery.

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Discussion

Based on our review of 199 carotid stenting procedures performed over a 9 ½ year period from December 2001 to June 2011, the 30-day MAE rate of stroke, death and MI was 8.5 %, and the 30-day mortality rate was 4.5 %.

When comparing the symptomatic versus the asymptomatic patients in our patient population, we noted a higher frequency of a) pre-existing carotid artery stenosis/occlusion b) previous CAS and c) IHD in the asymptomatic group. Despite the asymptomatic group having a higher frequency of these risk factors, the MAE rate was similar in both groups (symptomatic 8.9 % vs asymptomatic 7.9 %).

CREST results of primary composite endpoint of stroke/MI/death within 4 years are 7.2 % for CAS and 6.8 % for CEA, while ICSS interim results of stroke/death/MI within 120 days are 8.5 % for CAS and 5.2 % for CEA.  The ASA/AHA guidelines state that CAS is an alternative to CEA where the peri-procedural morbidity and mortality is between 4 % to 6 %. The authors of recent trials (CREST, ICSS) have acknowledged their lower complication rates compared to previous trials.

Our patient cohort is distinctly different from the patient population in the recent RCTs (CREST, ICSS), consisting of ‘real-world’ patients with multiple co-morbidities who are largely unsuitable for inclusion into RCTs. During the ICSS enrollment period (May 2001 to October 2008), only 4 patients from our centre successfully underwent randomisation. The other patients did not meet inclusion criteria. The surgical candidates received CEA and the remaining went for CAS. In the 10-year period between December 2001 and July 2011, more patients underwent CEA (n=234) than CAS (n=199).

At our centre, patients only undergo CAS following a vascular multidisciplinary meeting consisting of referring stroke physician, vascular surgeon and interventional neuroradiologist. Surgical candidates are selected for CEA and the candidates considered unsuitable for surgery due to high surgical risk are referred for CAS. Therefore, our patient cohort can be viewed as a high-risk group of patients primarily deemed unsuitable for randomisation into recent RCTs or unsuitable for surgery, with the only remaining option for carotid revascularisation of CAS.

Despite a higher-risk group of patients, the rate of the 30-day MAE of 8.5 % is equal to the 120-day ICSS peri-procedural adverse rate seen in suitably randomised patients. It is slightly higher than that seen in the CREST primary composite endpoint of 7.2%, but this may be explained by the fact that our patients are relatively high-risk. When comparing with a RCT with high-risk patients, the SAPPHIRE 30-day stroke/death rate in CAS was low (4.4 %). However the difference between our patient cohort and the SAPPHIRE RCT patients is that those patients were all suitable for randomisation for CEA or CAS. Given the inherent differences between our patient cohort and those in the RCTs, we believe that our results in this high-risk group are comparable to those seen in the ‘ideal’ patient population of the RCTs and, therefore, CAS performed at our institution is a safe and dependable method of carotid revascularisation.

Among the 8 patients who experienced a MAE of stroke/MI and not death, 7 made good-to-excellent recovery, with an mRS of 2 or less at clinic follow-up. This emphasises that the intermediate-to-long-term outcome of a stroke/MI MAE may improve considerably and not necessarily infer a poor clinical outcome. In practical terms, this is the outcome which is of most importance for the patient. Overall, therefore, our MAE with mRS greater than 2 is 5.0 % (n=10).

As we have demonstrated in our results, there is a trend to performing carotid artery stenting only in symptomatic patients. This is a reflection of ongoing improvement in medical therapy for stroke management over the last 10 years, with medical therapy being preferred for asymptomatic carotid artery stenosis.

An advantage of reviewing a single centre experience is that all the procedures were performed by 1 of 2 experienced interventional neuroradiologists with more than 30 cumulative years experience, thus reducing operator variability seen in the RCTs.

There are a number of limitations of this review including the relatively small number of patients over a number of years and the retrospective nature of the review.

A further limitation of our review is the lack of long-term clinical follow-up. As many of our patients may have been referred from outside institutions, long-term clinical follow-up would have been performed at the referring institution. In addition, in the ‘real-world’ scenario, not every centre would be as fortunate to have one of two experienced interventional neuroradiologists perform each CAS procedure, where the results would be biased towards fewer MAEs.

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Conclusion

The outcomes of CAS performed at our centre, in an unrestricted high-risk group of patients, compare favourably with those of recent RCTs. Despite a higher incidence of pre-existing carotid stenosis/occlusion/CAS and IHD in patients with asymptomatic disease, outcomes were similar to those of symptomatic patients. Our data suggests that CAS is a safe and dependable method of carotid revascularisation when offered as an alternative to CEA or if patients are unsuitable for CEA.

 

Conflict of interest

We declare that we have no conflict of interest.

References

  1. Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O’ Fallon WM, Wiebers DO; Ischaemic stroke subtypes: a population-based study of incidence and risk factors; Stroke 1999;30:2513-6
  2. Mayberg MR, Wilson SE, Yatsu F, Weiss DG, Messina L, Hershey LA, Colling C, Eskridge J, Deykin D, Winn HR, Veterans Affairs Cooperative Studies Program 309 Trialist Group; Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis; JAMA. 1991;266:3289-3294 [PubMed] [Full Text Sources]
  3. North American Symptomatic Carotid Endarterectomy Trial Collaboration; Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis; N Engl J Med. 1991;325:445-453
  4. European Carotid Surgery Trialists Collaborative Group; MCR European carotid surgery trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis; Lancet 1991;337:1235-1243
  5. Yadav JS, Wholey MH, Kuntz RE et al.; Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy Investigators. Protected Carotid-Artery Stenting versus Endarterectomy in High-Risk Patients; N Engl J Med. 2004;351:1493-501 [PubMed] [Full Text Sources]
  6. Brott TG, Hobson RW, Howard G, et al., the CREST investigators; Stenting versus Endarterectomy for Treatment of Carotid-Artery Stenosis; N Engl J Med 2010;363:11-23 [PubMed] [Full Text Sources]
  7. Ederle J, Dobson J, Featherstone RL, Bonati LH, van der Worp HB, et al., for the International Carotid Stenting Study investigators; 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;375:985-97 [PubMed] [Full Text Sources]
  8. The CAVATAS investigators; Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial; The Lancet 2001;357:1729-1737
  9. Mas JL, Chatellier G, Beyssen B, et al., the EVA-3S Investigators; Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis; N Engl J Med. 2006;355:1660-71 [PubMed] [Full Text Sources]
  10. Furie KL, Kasner SE, Adams RJ, et al.; Guidelines for the prevention of stroke in patients with stroke or transient ischaemic attack. Guidelines for the Prevention of Stroke in Patients With Stroke or Transient Ischaemic Attack: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association; Stroke 2011; 42:227-276: originally published online October 21, 2010
  11. The SPACE Collaborative Group, Ringleb P, Allenberg JR, et al.; 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial; Lancet 2006;368(9543):1239-47
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  13. Farrell B, Godwin J, Richards S, et al.; The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results; J Neurol Neurosurg Psychiatry 1991;54(12):1044-54 [PubMed] [Full Text Sources]