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Updated Society for Vascular Surgery guidelines for management of extracranial carotid disease

      Management of carotid bifurcation stenosis is a cornerstone of stroke prevention and has been the subject of extensive clinical investigation, including multiple controlled randomized trials. The appropriate treatment of patients with carotid bifurcation disease is of major interest to the community of vascular surgeons. In 2008, the Society for Vascular Surgery published guidelines for treatment of carotid artery disease. At the time, only one randomized trial, comparing carotid endarterectomy (CEA) and carotid stenting (CAS), had been published. Since that publication, four major randomized trials comparing CEA and CAS have been published, and the role of medical management has been re-emphasized. The current publication updates and expands the 2008 guidelines with specific emphasis on six areas: imaging in identification and characterization of carotid stenosis, medical therapy (as stand-alone management and also in conjunction with intervention in patients with carotid bifurcation stenosis), risk stratification to select patients for appropriate interventional management (CEA or CAS), technical standards for performing CEA and CAS, the relative roles of CEA and CAS, and management of unusual conditions associated with extracranial carotid pathology. Recommendations are made using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system, as has been done with other Society for Vascular Surgery guideline documents. The committee recommends CEA as the first-line treatment for most symptomatic patients with stenosis of 50% to 99% and asymptomatic patients with stenosis of 60% to 99%. The perioperative risk of stroke and death in asymptomatic patients must be <3% to ensure benefit for the patient. CAS should be reserved for symptomatic patients with stenosis of 50% to 99% at high risk for CEA for anatomic or medical reasons. CAS is not recommended for asymptomatic patients at this time. Asymptomatic patients at high risk for intervention or with <3 years life expectancy should be considered for medical management as the first-line therapy.

      Table of contents

      • I
        Indications for carotid bifurcation imaging
        • A
          Indications for imaging the neurologically symptomatic patient
        • B
          Indications for imaging the neurologically asymptomatic patient
          • 1
            Screening for asymptomatic carotid stenosis
            • a
              Screening patients with asymptomatic bruit
            • b
              Potential “high-risk groups” who might benefit from screening for asymptomatic stenosis
        • Recommendations for the use of carotid bifurcation imaging
      • II
        Selecting imaging modalities for carotid evaluation
        • A
          Carotid duplex ultrasound imaging
        • B
          Magnetic resonance imaging and angiography
        • C
          Computed tomography angiography
        • D
          Catheter-based digital subtraction arteriography
        • E
          Comparison of CDUS, MRA, CTA, and DSA
        • Recommendations for selection of carotid imaging modalities
      • III
        Medical management of patients with carotid stenosis
        • A
          Treatment of hypertension
        • B
          Treatment of diabetes mellitus
        • C
          Treatment of lipid abnormalities
        • D
          Smoking cessation
        • E
          Antithrombotic treatment
        • F
          Anticoagulant therapy
        • G
          Medical management for the perioperative period of CEA
        • H
          Medical management for the perioperative period of CAS
        • Recommendations for medical management of patients with carotid atherosclerosis
      • IV
        Technical recommendations for carotid interventions
        • A
          Carotid endarterectomy
        • B
          Carotid artery stenting
        • Recommendations regarding CEA and CAS technique
      • V
        Selecting the appropriate therapy: medical management, CAS, or CEA
        • A
          Assessing the risk associated with intervention
          • 1
            Anatomic and lesion characteristics
            • a
              Lesion location
            • b
              Lesion characteristics
            • c
              Other anatomic considerations
          • 2
            Patient characteristics
        • B
          Neurologically asymptomatic patients with ≥60% carotid artery stenosis
          • 1
            CEA for asymptomatic lesions
          • 2
            CAS in asymptomatic lesions
          • 3
            Medical management of asymptomatic carotid stenosis
        • C
          Neurologically symptomatic patients with ≥50% carotid artery disease
          • 1
            CEA in symptomatic stenosis
          • 2
            CAS in symptomatic stenosis
        • D
          Meta-analysis: CEA vs CAS
        • Recommendations for selecting therapy
      • VI
        Unusual conditions associated with carotid stenosis
        • A
          Acute neurologic syndromes
          • 1
            Management of acute stroke
            • a
              Presentation within 0-6 hours
            • b
              Presentation later than 6 hours
          • 2
            Stroke in evolution (fluctuating neurologic deficits)
          • 3
            Crescendo TIA
          • 4
            Acute postintervention stroke/occlusion
        • Recommendations for management of acute neurologic syndromes
        • B
          ICA occlusion with persistent symptoms/external carotid stenosis
        • Recommendations for management of symptomatic ICA occlusion
        • C
          Carotid dissection
        • Recommendations for management of carotid dissection
        • D
          Combined carotid and coronary disease
        • Recommendations for management of combined carotid and coronary disease
      Management of extracranial carotid disease has been the focus of intense investigation and debate by multiple medical specialists since the introduction of carotid endarterectomy (CEA) as a therapeutic option for the treatment and prevention of stroke more than half a century ago. Initial hopes that CEA could reverse the clinical course of stroke were proven false, and the role of surgical management of extracranial carotid and vertebral obstructions was defined by one of the earliest efforts at a multicentered randomized clinical trial, The Joint Study on The Extracranial Circulation.
      • Fields W.S.
      • North R.R.
      • Hass W.K.
      • Kircheff I.I.
      • Chase N.E.
      • Bauer R.B.
      • et al.
      Joint study of extracranial arterial occlusion as a cause of Stroke I. Organization of study and survey of patient population.
      The results of this decade-long study, involving 5000 patients, established the role of CEA in the treatment of minor stroke, transient ischemic attack (TIA), and amaurosis fugax, confirmed that surgery had a limited role in the treatment of established stroke, and established the limited role of vertebral reconstruction in the treatment of cerebral insufficiency. Over the ensuing decades, surgical results of CEA improved, asymptomatic carotid stenosis was increasingly identified by noninvasive studies, and CEA assumed a primarily prophylactic role as prevention of major stroke in asymptomatic patients or those with evidence of transient cerebral or ocular ischemia. Large randomized trials
      North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET)
      Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      • Barnett H.J.
      • Taylor D.W.
      • Eliasziw M.
      • Fox A.J.
      • Ferguson G.G.
      • Haynes R.B.
      • et al.
      Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      have established the role and efficacy of carotid endarterectomy (CEA) in stroke prevention.
      In the last decade, carotid artery stenting (CAS) has emerged as a catheter-based alternative to CEA, and medical therapy for stroke treatment and prevention has evolved. Currently, approximately 135,000 interventions on lesions in the carotid bifurcation are being performed annually in the United States, by a variety of specialists, including vascular surgeons, general surgeons, thoracic surgeons, neurosurgeons, cardiologists, interventional radiologists, and interventional neurologists.
      • Eslami M.H.
      • McPhee J.T.
      • Simons J.P.
      • Schanzer A.
      • Messina L.M.
      National trends in utilization and postprocedure outcomes for carotid revascularization 2005 to 2007.
      • Cowan J.A.
      • Dimick J.B.
      • Thompson B.C.
      • Stanley J.A.
      • Upchurch G.R.
      Surgeon volume as an indicator of outcomes after carotid endarterectomy: an effect independent of specialty practice and hospital volume.
      Approximately 11% of these interventions are catheter-based, and 90% of interventions are in patients without neurologic symptoms.
      • Eslami M.H.
      • McPhee J.T.
      • Simons J.P.
      • Schanzer A.
      • Messina L.M.
      National trends in utilization and postprocedure outcomes for carotid revascularization 2005 to 2007.
      As in any situation where there are multiple options for the treatment of a single condition, defining optimal treatment can be difficult. This is further compounded when multiple specialists, often with nonoverlapping expertise, are involved in the treatment of the patient. As a result, a voluminous and often conflicting literature has developed around the current standards of diagnosis and management of extracranial carotid stenosis. Recently two large, prospective, randomized trials have been published comparing the efficacy of CEA and CAS in the management of extracranial carotid stenosis.
      • Brott T.G.
      • Hobson 2nd, R.W.
      • Howard G.
      • Roubin G.S.
      • Clark W.M.
      • Brooks W.
      • et al.
      Stenting versus endarterectomy for treatment of carotid-artery stenosis.
      • Ederle J.
      • Dobson J.
      • Featherstone R.L.
      • Bonati L.H.
      • van der Worp H.B.
      • et al.
      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.
      A meta-analysis comparing CAS and CEA, including these trials has recently been published in the Journal of Vascular Surgery.
      • Murad M.H.
      • Shahrour A.
      • Shah N.D.
      • Montori V.M.
      • Ricotta J.J.
      A systematic review and meta-analysis of randomized trials of carotid endarterectomy vs stenting.
      In 2008, the Society for Vascular Surgery published clinical practice guidelines for the management of extracranial carotid artery disease in the Journal of Vascular Surgery.
      • Hobson 2nd, R.W.
      • Mackey W.C.
      • Ascher E.
      • Murad M.H.
      • Calligaro K.D.
      • Comerota A.J.
      • et al.
      Management of atherosclerotic carotid artery disease: clinical practice guidelines of the Society for Vascular Surgery.
      More recently, a multispecialty document has been published on the “Management of Patients with Extracranial Carotid and Vertebral Artery Disease.”
      • Brott T.G.
      • Halperin J.L.
      • Abbara S.
      • Bacharach J.M.
      • Barr J.D.
      • Bush R.L.
      • et al.
      2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery Developed in Collaboration With the American Academy of Neurology and Society of Cardiovascular Computed Tomography.
      This extensive document represents an effort to evaluate the existing literature on extracranial carotid and vertebral disease and is an important reference.
      The data contained in the recently published randomized trials has prompted the Society for Vascular Surgery to publish an update of its 2008 guidelines, confined to management of extracranial carotid artery disease. This is particularly appropriate because vascular surgeons play a major if not predominant role in the management of patients with carotid bifurcation disease.
      In developing these recommendations, the committee placed more weight on the reduction of stroke and death and less on the importance of nonfatal myocardial infarction (MI). Because the latter end point often represents the main benefit of CAS, the recommendations in this document are more circumspect with regard to the role of CAS and more supportive of the role of CEA than the recommendations of the American Heart Association (AHA) guidelines committee. This document is divided into six major sections:
      • I
        Indications for imaging of the extracranial circulation
      • II
        Selection of imaging modality
      • III
        The importance of medical therapy in the overall management of patients with carotid stenosis, including medical management in the peri-intervention period.
      • IV
        Technical considerations for performing CEA and CAS
      • V
        The relative roles of medical management, CEA and CAS for stroke risk reduction in patients with carotid stenosis based on review of the literature, with particular reference to risk factor stratification and the most recent completed trials
      • VI
        The management of unusual conditions associated with extracranial carotid pathology, including acute neurologic conditions, symptomatic carotid occlusion, carotid dissection, and patients with carotid stenosis in need of coronary artery revascularization
      The committee reviewed the literature pertinent to each of the six areas and provided recommendations for treatment using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system.
      • Murad M.H.
      • Montori V.M.
      • Sidawy A.N.
      • Ascher E.
      • Meissner M.H.
      • Chaikof E.L.
      • et al.
      Guideline methodology of the Society for Vascular Surgery including the experience with the GRADE framework.
      This system, adopted by more than 40 other organizations, incorporates an evaluation of the strength of the evidence and the risks/benefits of implementing the recommendation. For the purposes of this review, we placed the highest priorities on reducing overall stroke risk, periprocedural stroke risk, and periprocedural mortality. Lesser importance was given to reducing nonfatal MI, cost, and the ability to perform a percutaneous procedure. Recommendations are characterized as strong GRADE 1 or weak GRADE 2, based on the quality of evidence, the balance between desirable effects and undesirable ones, the values and preferences, and the resources and costs.
      GRADE 1 recommendations are meant to identify practices where benefit clearly outweighs risk. These recommendations can be made by clinicians and accepted by patients with a high degree of confidence. GRADE 2 recommendations are made when the benefits and risks are more closely matched and are more dependent on specific clinical scenarios. In general, physician and patient preference plays a more important role in the decision-making process in these circumstances.
      In addition to the GRADE of recommendation, the level of evidence to support the recommendation is noted. Evidence is divided into 3 categories: A (high quality), B (moderate quality), and C (low quality). Conclusions based on high-quality evidence are unlikely to change with further study, those based on moderate-quality evidence are more likely to be affected by further investigation, and those based on low-quality evidence are the least supported by current data and the most likely to be subject to change in the future.
      It is important to note that a GRADE 1 recommendation can be made based on low-quality (C) evidence by the effect on patient outcome. For example, although there are little data on the efficacy of CEA in asymptomatic patients with <60% stenosis, one can recommend with confidence that CEA not be performed in these patients. A full explanation of the GRADE system is presented in the recent article by Murad et al
      • Murad M.H.
      • Montori V.M.
      • Sidawy A.N.
      • Ascher E.
      • Meissner M.H.
      • Chaikof E.L.
      • et al.
      Guideline methodology of the Society for Vascular Surgery including the experience with the GRADE framework.
      referenced earlier. It is important to note that this grading system differs somewhat from the one used in the recent American College of Cardiology (ACC)/AHA Task force report.
      • Brott T.G.
      • Halperin J.L.
      • Abbara S.
      • Bacharach J.M.
      • Barr J.D.
      • Bush R.L.
      • et al.
      2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery Developed in Collaboration With the American Academy of Neurology and Society of Cardiovascular Computed Tomography.
      Each member of the committee was assigned responsibility for compiling information pertinent to a specific area of the document. These data were distributed to all members for review, and each area was subsequently discussed in conference calls. A consensus of the recommendation and level of evidence to support it was reached. Each recommendation in this document represents the unanimous opinion of the task force. Although some recommendations are GRADE 2 with Level 3 data, the task force felt it appropriate to present these as the unanimous opinion of its members regarding optimal current management. This was done with the recognition that such recommendations could change in the future but that it was unlikely that new data would emerge soon. These guidelines are likely to be a “living document” that will change as techniques are further refined, technology develops, medical therapy improves, and new data emerge.

      I. Indications for carotid bifurcation imaging

      Stroke is the third leading cause of death, behind coronary artery disease (CAD) and cancer, and is the leading cause of disability in the United States and Western Europe. Approximately 80% of strokes are ischemic and 20% are hemorrhagic.
      • Warlow C.P.
      • Dennis M.S.
      • van Gijn J.
      What caused the transient or persisting ischaemic event.
      Significant carotid stenosis (>50%) is seen in 12% to 20% of all anterior circulation ischemic strokes, which is two to three times higher than the risk for less severe asymptomatic stenosis.
      • Chambers B.R.
      • Donnan G.A.
      Carotid endarterectomy for asymptomatic carotid stenosis.
      • Abbott A.L.
      • Bladin C.F.
      • Levi C.R.
      • Chambers B.R.
      What should we do with asymptomatic carotid stenosis?.
      Unfortunately, only 15% of stroke victims have a warning TIA before stroke, and waiting until symptoms occur is not ideal.
      • Hankey G.J.
      Impact of treatment of people with transient ischemic attacks on stroke incidence and public health.
      The purpose of carotid bifurcation imaging is to detect “stroke-prone” carotid bifurcation plaque and identify a high-risk patient likely to benefit from therapy designed to reduce stroke risk.
      Stroke risk is dependent on many factors, but for patients with carotid bifurcation disease, the most important are a history of neurologic symptoms, the degree of stenosis of the carotid bifurcation plaque, and to a lesser extent, plaque characteristics such as ulcerations, intraplaque hemorrhage, and lipid content.
      The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) clearly demonstrated the efficacy of CEA in reducing stroke in patients with symptoms of carotid territory cerebral ischemia and carotid bifurcation stenosis that reduced luminal diameter by >50%.
      North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET)
      Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      • Barnett H.J.
      • Taylor D.W.
      • Eliasziw M.
      • Fox A.J.
      • Ferguson G.G.
      • Haynes R.B.
      • et al.
      Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).
      In these studies, the risk of stroke was higher in patients with a clear history of carotid territory ischemic events (as opposed to amaurosis fugax), and stroke risk increased with the severity of stenosis. Asymptomatic Carotid Atherosclerosis Study (ACAS) and Asymptomatic Carotid Surgery Trial (ACST)
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      found that CEA was also effective in reducing stroke risk in patients with asymptomatic carotid stenosis >60%, although the stroke risk inherent in an asymptomatic stenosis was much less than that in a symptomatic lesion. It follows then that neurologically symptomatic patients and neurologically asymptomatic patients at high risk for harboring a carotid stenosis of ≥60% would be candidates for carotid bifurcation imaging.

      Indications for imaging the neurologically symptomatic patient

      Typical carotid territory ischemic symptoms include contralateral weakness of the face, arm, or leg, or both; contralateral sensory deficit or paresthesia of the face, arm, or leg, or both; or transient ipsilateral blindness (amaurosis fugax). If the right cerebral hemisphere is involved, other manifestations may be noted, including anosognosia, asomatognosia, neglect, visual, or sensory extinction. If the left hemisphere is involved, patients may show manifestation of aphasia, alexia, anomia, and agraphesthesia. Symptoms not typically associated with carotid territory events include vertigo, ataxia, diplopia, visual disturbances, dysarthria, nausea, vomiting, decreased consciousness, and weakness, which may include quadriparesis.
      The physical examination may show signs of stroke: facial/eyelid drooping, motor or sensory deficits, and speech disturbances. Ocular examinations can occasionally identify Hollenhorst plaques. Neck auscultation may elicit carotid bruit; however, the absence of a neck bruit does not exclude the possibility of a significant carotid bifurcation lesion. Given the incidence of significant carotid stenosis in patients who present with stroke
      • Warlow C.P.
      • Dennis M.S.
      • van Gijn J.
      What caused the transient or persisting ischaemic event.
      • Chaturvedi S.
      • Bruno A.
      • Feasby T.
      • Holloway R.
      • Benavente O.
      • Cohen S.N.
      • et al.
      Carotid Endarterectomy – an evidence based review: report of the Therapeutics and Technology Subcommittee of the American Academy of Neurology.
      and the effectiveness of CEA in reducing stroke in symptomatic patients with >50% carotid stenosis,
      North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET)
      Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      • Barnett H.J.
      • Taylor D.W.
      • Eliasziw M.
      • Fox A.J.
      • Ferguson G.G.
      • Haynes R.B.
      • et al.
      Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).
      it is important to evaluate the carotid bifurcation in every patient with symptoms of carotid territory ischemia.
      Amaurosis fugax or the finding of a Hollenhorst plaque on funduscopic examination, or both, is also correlated with the presence of significant carotid bifurcation stenosis. However, neither amaurosis fugax nor identification of a Hollenhorst plaque are associated with the same stroke risk as transient cerebral ischemia.
      • Benavente O.
      • Eliasziw M.
      • Streifler J.Y.
      • Fox A.J.
      • Barnett H.J.
      • Meldrum H.
      • et al.
      Prognosis after transient monocular blindness associated with carotid-artery stenosis.
      Identification of carotid stenosis in that clinical scenario implies a stroke risk somewhere between a neurologically symptomatic patient and one who is asymptomatic.

      Indications for imaging the neurologically asymptomatic patient

      Evaluation and treatment of patients who are neurologically asymptomatic is much more controversial. The benefit of carotid endarterectomy for stenosis >60%, although statistically significant in large trials, is much less than for neurologically symptomatic individuals and rests on the premise that intervention can be performed with minimal morbidity.
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      Identification of these asymptomatic patients may occur by routine screening using duplex ultrasound (DUS) imaging or selective application of DUS imaging to high-risk individuals.

       1. Screening for asymptomatic carotid stenosis

      To date, there is no consensus on which patients should undergo carotid screening for the detection of carotid stenosis. The American Society of Neuroimaging
      • Qureshi A.I.
      • Alexandrov A.V.
      • Tegeler C.H.
      • Hobson 2nd, R.W.
      • Dennis Baker J.
      • Hopkins L.N.
      • et al.
      Guidelines for screening of extracranial carotid artery disease: a statement for healthcare professionals from the multidisciplinary practice guidelines committee of the American Society of Neuroimaging: cosponsored by the Society of Vascular and Interventional Neurology.
      concluded that the efficacy of screening would be related to the prevalence of the disease in the screened populations. When the prevalence of stenosis is ≥20%, screening reduced risk of stroke in a cost-effective manner, with intermediate prevalence of between 5% and 20%: screening reduced the risk of stroke in a cost-effective manner in some studies; however, the benefit was usually marginal and was lost if complications of the intervention >5%. With a prevalence of <5%, screening has not been shown to reduce the risk of stroke in a cost-effective manner and may be harmful.
      Given these assumptions, screening of the general population is not indicated. This position is supported by multiple professional organizations, including the National Stroke Association,
      • Gorelick P.B.
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      • Mustone-Alexander L.
      • Rader D.
      • et al.
      Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association.
      the Canadian Stroke Consortium
      • Perry J.R.
      • Szalai J.P.
      • Norris J.W.
      Consensus against both endarterectomy and routine screening for asymptomatic carotid artery stenosis. Canadian Stroke Consortium.
      and the U.S. Preventive Services Task Force.
      U.S. Preventive Services Task Force
      Screening for carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement.
      The American Stroke Association/AHA Stroke Council
      • Goldstein L.B.
      • Adams R.
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      • Appel L.J.
      • Brass L.M.
      • Bushnell C.D.
      • et al.
      Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: the American Academy of Neurology affirms the value of this guideline.
      concluded that highly selected patient populations may benefit, but screening of the general population for asymptomatic carotid stenosis was unlikely to be cost-effective and might have the potential adverse effect of false-negative or false-positive results. Finally, the American College of Cardiology Foundation, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and American Society of Interventional & Therapeutic Neuroradiology Clinical Expert Consensus Panel on Carotid Stenting recommended screening for asymptomatic patients with carotid bruit who are potential candidates for carotid intervention and for those in whom coronary artery bypass grafting (CABG) is planned.
      • Bates E.R.
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      • Duckwiler G.R.
      • Feldman T.E.
      • et al.
      ACCF/SCAI/SVMB/SIR/ASITN 2007 clinical expert consensus document on carotid stenting: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (ACCF/SCAI/SVMB/SIR/ASITN Clinical Expert Consensus Document Committee on Carotid stenting).

       a. Screening patients with asymptomatic bruit

      Zhu and Norris,
      • Zhu C.Z.
      • Norris J.W.
      Role of carotid stenosis in ischemic stroke.
      in the largest reported study of carotid screening in asymptomatic patients, reported the prevalence of carotid stenosis >75% for those with a carotid bruit was 1.2%. Although the presence of a neck bruit has not been found to predict carotid stenosis >60% in a neurologically asymptomatic population,
      • Zhu C.Z.
      • Norris J.W.
      Role of carotid stenosis in ischemic stroke.
      focal ipsilateral carotid bruits in neurologically symptomatic patients had a sensitivity of 63% and a specificity of 61% for high-grade carotid stenosis (range, 70%-99%).
      • Sauvé J.S.
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      • et al.
      Can bruits distinguish high-grade from moderate symptomatic carotid stenosis? The North American Symptomatic Carotid Endarterectomy Trial.
      The absence of a bruit did not significantly change the probability of significant stenosis in this group of patients (pretest, 52%; post-test, 40%). Ratchford et al
      • Ratchford E.V.
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      • et al.
      Carotid bruit for the detection of hemodynamically significant carotid stenosis: the Northern Manhattan Study.
      found in a selected high-risk subgroup of asymptomatic patients that if a bruit was heard, 25% had a >60% stenosis. The presence of carotid bruit has been shown to increase the absolute risk of stroke,
      • Heyman A.
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      • et al.
      Risk of stroke in asymptomatic persons with cervical arterial bruits: a population study in Evans County, Georgia.
      • Wiebers D.O.
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      Prospective comparison of a cohort with asymptomatic carotid bruit and a population-based cohort without carotid bruit.
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      • et al.
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      MI, and death.
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      • Atwood E.
      Carotid bruits as a prognostic indicator of cardiovascular death and myocardial infarction: a meta-analysis.
      In general population-based studies, the prevalence of severe bifurcation stenosis is not high enough to make bruit alone an indication for carotid screening. With these facts in mind, screening should be pursued only if a bruit is associated with other risk factors for stenosis and stroke in patients who have a low operative risk
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      • Hobson 2nd, R.W.
      • Mackey W.C.
      • Ascher E.
      • Murad M.H.
      • Calligaro K.D.
      • Comerota A.J.
      • et al.
      Management of atherosclerotic carotid artery disease: clinical practice guidelines of the Society for Vascular Surgery.
      • Benavente O.
      • Moher D.
      • Pham B.
      Carotid endarterectomy for asymptomatic carotid stenosis: a meta-analysis.
      and are willing to undergo carotid intervention, whether CEA or CAS.

       b. Potential “high-risk groups” who might benefit from screening for asymptomatic stenosis

      Two studies have identified specific groups among the general population with a higher prevalence of significant carotid stenosis that may >30%. Jacobowitz et al
      • Jacobowitz G.R.
      • Rockman C.B.
      • Gagne P.J.
      • Adelman M.A.
      • Lamparello P.J.
      • Landis R.
      • et al.
      A model for predicting occult carotid artery stenosis: screening is justified in a selected population.
      developed a model identifying patients at high risk for >50% asymptomatic carotid stenosis. The screened patients were aged >60 years and had one or more of the following risk factors: history of hypertension, CAD, current smoking, and a first-degree family relative with a history of stroke. The prevalence of carotid artery stenosis was only 2% if no risk factor was present, 6% with one risk factor, which increased to 14% for two risk factors, to 16% for three risk factors, and to 67% for four risk factors.
      Qureshi et al
      • Qureshi A.I.
      • Janardhan V.
      • Bennett S.E.
      • Luft A.R.
      • Hopkins L.N.
      • Guterman L.R.
      Who should be screened for asymptomatic carotid artery stenosis? Experience from the Western New York stroke screening program.
      identified the following variables associated with ≥60% asymptomatic carotid stenosis: age >65 years (odds ratio, 4.1), current smoking (odds ratio, 2), CAD (odds ratio, 2.4), and hypercholesterolemia (odds ratio, 1.9). Patients undergoing coronary revascularization are another group with an increased prevalence of carotid stenosis of 2% to 27%.
      • Ascher E.
      • Hingorani A.
      • Yorkovich W.
      • Ramsey P.J.
      • Salles-Cunha S.
      Routine preoperative carotid duplex scanning in patients undergoing open heart surgery: is it worthwhile?.
      • Naylor A.R.
      • Mehta Z.
      • Rothwell P.M.
      • Bell P.R.
      Carotid artery disease and stroke after coronary artery bypass: a critical review of the literature.
      Overall, the prevalence of carotid artery stenosis among patients undergoing CABG is higher than the general population. In patients with symptomatic CAD and other risk factors, such as age >65 years, history of stroke or TIA, left main coronary stenosis, diabetes mellitus, carotid bruit, peripheral arterial disease (PAD), and previous carotid operation, it is feasible that a subset of patients with a prevalence >20% can be identified who might benefit from carotid screening.
      • Ascher E.
      • Hingorani A.
      • Yorkovich W.
      • Ramsey P.J.
      • Salles-Cunha S.
      Routine preoperative carotid duplex scanning in patients undergoing open heart surgery: is it worthwhile?.
      • D'Agostino R.S.
      • Svensson L.G.
      • Neumann D.J.
      • Balkhy H.H.
      • Williamson W.A.
      • Shahian D.M.
      Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients.
      • Fukuda I.
      • Ohuchi H.
      • Sato M.
      • Sato F.
      • Wada M.
      Carotid screening with duplex scanning before coronary artery bypass.
      • Hill A.B.
      Should patients be screened for asymptomatic carotid artery stenosis?.
      • Ascher E.
      • DePippo P.
      • Salles-Cunha S.
      • Marchese J.
      • Yorkovich W.
      Carotid screening with duplex ultrasound in elderly asymptomatic patients referred to a vascular surgeon: is it worthwhile?.
      • Hill A.B.
      • Obrand D.
      • Steinmetz O.K.
      The utility of selective screening for carotid stenosis in cardiac surgery patients.
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr, L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      • Tanimoto S.
      • Ikari Y.
      • Tanabe K.
      • Yachi S.
      • Nakajima H.
      • Nakayama T.
      • et al.
      Prevalence of carotid artery stenosis in patients with coronary artery disease in Japanese population.
      The ACC/AHA guidelines
      • Eagle K.A.
      • Guyton R.A.
      • Davidoff R.
      • Edwards F.H.
      • Ewy G.A.
      • Gardner T.J.
      • et al.
      ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to update the 1999 guidelines for coronary artery bypass graft surgery).
      note that carotid screening before CABG is probably indicated in the following subset of patients: age >65 years, left main coronary stenosis, history of smoking, history of TIA/stroke or carotid bruit, and PAD.
      Several studies
      • Marek J.
      • Mills J.L.
      • Harvich J.
      • Cui H.
      • Fujitani R.M.
      Utility of routine carotid duplex screening in patients who have claudication.
      • Alexandrova N.A.
      • Gibson W.C.
      • Norris J.W.
      • Maggisano R.
      Carotid artery stenosis in peripheral vascular disease.
      • Valentine R.J.
      • Hagino R.T.
      • Boyd P.I.
      • Kakish H.B.
      • Clagett G.P.
      Utility of carotid duplex in young adults with lower extremity atherosclerosis: how aggressive should we be in screening young patients?.
      • Cheng S.W.
      • Wu L.L.
      • Ting A.C.
      • Lau H.
      • Wong J.
      Screening for asymptomatic carotid stenosis in patients with peripheral vascular disease: a prospective study and risk factor analysis.
      • House A.K.
      • Bell R.
      • House J.
      • Mastaglia F.
      • Kumar A.
      • D'Antuono M.
      Asymptomatic carotid artery stenosis associated with peripheral vascular disease: a prospective study.
      have suggested that the prevalence of ≥60% carotid artery stenosis among patients with symptomatic PAD is >20%, regardless of the patient's age. However, the prevalence of ≥60% carotid artery stenosis among patients with abdominal aortic aneurysms (AAA) is <20%.
      • Deville C.
      • Kerdi S.
      • Madonna F.
      • de la Renaudière D.F.
      • Labrousse L.
      Infrarenal abdominal aortic aneurysm repair: detection and treatment of associated carotid and coronary lesions.
      • Cahan M.A.
      • Killewich L.A.
      • Kolodner L.
      • Powell C.C.
      • Metz M.
      • Sawyer R.
      • et al.
      The prevalence of carotid artery stenosis in patients undergoing aortic reconstruction.
      • Axelrod D.A.
      • Diwan A.
      • Stanley J.C.
      • Jacobs L.A.
      • Henke P.K.
      • Greenfield L.J.
      • et al.
      Cost of routine screening for carotid and lower extremity occlusive disease in patients with abdominal aortic aneurysms.
      This suggests that screening patients with AAA would have only a modest benefit and only if intervention could be performed with low morbidity and mortality.
      • Perry J.R.
      • Szalai J.P.
      • Norris J.W.
      Consensus against both endarterectomy and routine screening for asymptomatic carotid artery stenosis. Canadian Stroke Consortium.
      Because there is no evidence that stroke risk after AAA repair is increased by the presence of carotid stenosis, routine carotid screening of AAA patients is not indicated.
      In patients with prior head and neck radiotherapy, the prevalence of significant carotid artery stenosis may be high enough, depending on the time between radiotherapy exposure and screening, to justify routine carotid screening.
      • Cheng S.W.
      • Wu L.L.
      • Ting A.C.
      • Lau H.
      • Lam L.K.
      • Wei W.I.
      Irradiation-induced extracranial carotid stenosis in patients with head and neck malignancies.
      • Moritz M.W.
      • Higgins R.F.
      • Jacobs J.R.
      Duplex imaging and incidence of carotid radiation injury after high-dose radiotherapy for tumors of the head and neck.
      • Dubec J.J.
      • Munk P.L.
      • Tsang V.
      • Lee M.J.
      • Janzen D.L.
      • Buckley J.
      • et al.
      Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy.
      • Carmody B.J.
      • Arora S.
      • Avena R.
      • Curry K.M.
      • Simpkins J.
      • Cosby K.
      • et al.
      Accelerated carotid artery disease after high-dose head and neck radiotherapy: is there a role for routine carotid duplex surveillance?.
      • Steele S.R.
      • Martin M.J.
      • Mullenix P.S.
      • Crawford J.V.
      • Cuadrado D.S.
      • Andersen C.A.
      Focused high-risk population screening for carotid arterial stenosis after radiation therapy for head and neck cancer.
      The highest incidence is generally observed 15 years after radiotherapy exposure, with 21.3% and 5.3% rates of ipsilateral and contralateral stenosis, respectively. The data also suggest that the ipsilateral common carotid (CCA) and internal carotid arteries (ICA) are both involved. The rate of contralateral carotid artery stenosis may also be higher than that observed in the general population.
      Unfortunately, limited data are available regarding carotid screening after radiotherapy among patients with head and neck cancer. However, the distribution of disease and clinical course in patients after radiation for head and neck malignancy is different from that of the typical atherosclerotic population. There is a higher incidence of diffuse disease, often involving the CCA, and many of these patients remain neurologically asymptomatic. Further, CEA in this group is considered relatively “high risk,” and prior radiotherapy is a relative indication for CAS rather than CEA. There are no robust data on the long-term results of CAS in asymptomatic stenosis associated with prior radiotherapy. Therefore, issues other than the increased prevalence of disease must be considered in formulating recommendations concerning screening in this group of patients.
      Brain imaging will occasionally identify patients who have evidence of focal cerebral infarction despite the absence of any history of neurologic symptoms and a normal result on the neurologic examination. These infarcts can vary in size and are often found in the frontal lobes or the nondominant temporal lobe. They may occur as small symmetric lacunar infarcts, implying small-vessel disease, or they may also be asymmetric, which tends to implicate ipsilateral carotid stenosis. These can be secondary to blood flow changes distal to carotid occlusion, which may increase the risk of lacunar infarcts in those with small vessel disease. However, Kakkos et al
      • Kakkos S.K.
      • Sabetai M.
      • Tegos T.
      • Stevens J.
      • Thomas D.
      • Griffin M.
      • et al.
      Silent embolic infarcts on computed tomography brain scans and risk of ipsilateral hemispheric events in patients with asymptomatic internal carotid artery stenosis.
      reported a higher stroke rate of 4.4% vs 1.3% in patients with 60% to 79% clinically asymptomatic stenosis if a silent infarct was present. Carotid screening is recommended in patients with asymptomatic infarctions.
      Recommendations for the use of carotid bifurcation imaging
      • 1
        Imaging of the cervical carotid artery is recommended in all patients with symptoms of carotid territory ischemia. This recommendation is based on the significant incidence of clinically relevant carotid stenosis in this patient group and the efficacy of CEA for clinically significant lesions in reducing overall stroke (GRADE 1, Level of Evidence A).
      • 2
        Imaging should be strongly considered for patients who present with amaurosis fugax, evidence of retinal artery embolization on funduscopic examination, or asymptomatic cerebral infarction, and are candidates for CEA. This recommendation is based on the intermediate stroke risk in this group of patients and the efficacy of CEA in reducing risk of subsequent stroke (GRADE 1, Level of Evidence A).
      • 3
        Routine screening is not recommended to detect clinically asymptomatic carotid stenosis in the general population. Screening is not recommended for presence of a neck bruit alone without other risk factors. This recommendation is based on the low prevalence of disease in the population at large, including those with neck bruits, as well as the potential harm of indiscriminate application of carotid bifurcation intervention to a large number of asymptomatic individuals (GRADE 1, Level of Evidence A).
      • 4
        Screening for asymptomatic clinically significant carotid bifurcation stenosis should be considered in certain groups of patients with multiple risk factors that increase the incidence of disease as long as the patients are fit for and willing to consider carotid intervention if a significant stenosis is discovered. The presence of a carotid bruit in these patients increases the likelihood of a significant stenosis (GRADE 1, Level of Evidence B). Such groups of patients include:
        • a
          Patients with evidence of clinically significant peripheral vascular disease regardless of age.
        • b
          Patients aged ≥65 years with a history of one or more of the following atherosclerotic risk factors: CAD, smoking, or hypercholesterolemia. In general, the more risk factors present, the higher the yield of screening should be expected.
      • 5
        Carotid screening may be considered in patients before CABG. This is most likely to be fruitful if the patients are aged >65 years and have left main disease or a history of peripheral vascular disease. The strongest indication for screening these patients from the data available is to identify patients at high risk for perioperative stroke (GRADE 2, Level of Evidence B).
      • 6
        Carotid screening is not recommended for patients with AAA who do not fit into one of the above categories (GRADE 2, Level of Evidence B).
      • 7
        Carotid screening is not recommended for asymptomatic patients who have undergone prior head and neck radiotherapy. Although the incidence of disease is increased in this group of patients, the utility of intervention in the absence of neurologic symptoms has not been clearly established (GRADE 2, Level of Evidence B).

      II. Selecting imaging modalities for carotid evaluation

      The two most important features of carotid bifurcation atheroma are the degree of diameter stenosis and the character of the bifurcation plaque. In addition to information about the carotid bifurcation, there are clinical scenarios where the clinician requires information on the status of the vessels proximal or distal to the cervical carotid artery. These factors need to be considered when choosing between imaging studies. It is common—but not universal—to use multiple modalities when evaluating a patient with suspected cervical carotid stenosis.
      In NASCET
      North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET)
      Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      • Barnett H.J.
      • Taylor D.W.
      • Eliasziw M.
      • Fox A.J.
      • Ferguson G.G.
      • Haynes R.B.
      • et al.
      Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      and ECST,
      Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).
      a higher degree of stenosis in symptomatic patients was associated with a higher stroke risk. The ACAS
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      found no correlation between the severity of carotid stenosis and the incidence of stroke; however, there were too few strokes in this study to permit a subgroup analysis of the effect of degree of stenosis on the ability to benefit from CEA. Angiographic data from the ECST study
      Risk of stroke in the distribution of an asymptomatic carotid artery. The European Carotid Surgery Trialists Collaborative Group.
      on contralateral asymptomatic carotid arteries from 2295 patients demonstrated a <2% annual stroke risk in patients with <70% neurologically asymptomatic stenosis. Asymptomatic lesions with greater degrees of stenosis had a greater risk of stroke: 9.8% for patients with 70% to 79% stenosis and 14.4% for those with 80% to 99% stenosis. These data suggest that the degree of stenosis is a marker of stroke risk in symptomatic and asymptomatic lesions. Pathologic studies have demonstrated that more stenotic carotid plaques are more likely to have ulceration, intraplaque hemorrhage, and intraluminal thrombus formation, all of which are clearly related to cerebral embolization and stroke.
      • Ricotta J.J.
      • Schenck E.A.
      • Hassett J.M.
      • Deweese J.A.
      Lesion Width as a Discriminator of Plaque Characteristics.
      Plaque morphology is an important feature in assessing future risk of neurologic events. Heterogeneous plaques have been shown to increase the risk of neurologic symptoms (TIA/stroke)
      • Reilly L.M.
      • Lusby R.J.
      • Hughes L.
      • Ferrell L.D.
      • Stoney R.J.
      • Ehrenfeld W.K.
      Carotid plaque histology using real-time ultrasonography Clinical and therapeutic implications.
      • AbuRahma A.F.
      • Wulu J.T.
      • Crotty B.
      Carotid plaque ultrasonic heterogeneity and severity of stenosis.
      and were also associated with an incidence of TIA/stroke that was higher than that in homogenous plaques for all grades of stenosis.
      • AbuRahma A.F.
      • Wulu J.T.
      • Crotty B.
      Carotid plaque ultrasonic heterogeneity and severity of stenosis.
      Using DUS imaging and computerized image analysis
      • Nicolaides A.N.
      Asymptomatic carotid stenosis and risk of stroke: identification of a high risk group (ACRS): a natural history study.
      quantifying the gray scale median of the plaque, Biasi et al
      • Biasi G.M.
      • Froio A.
      • Diethrich E.B.
      • Deleo G.
      • Galimberti S.
      • Mingazzini P.
      • et al.
      Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) Study.
      demonstrated that gray scale median values of ≤25 were associated with an increased stroke risk of carotid stenting procedures.
      Nicolaides et al
      • Nicolaides A.N.
      • Kakkos S.K.
      • Griffin M.
      • Sabetai M.
      • Dhanjil S.
      • Thomas D.J.
      • et al.
      Effect of image normalization on carotid plaque classification and the risk of ipsilateral hemispheric ischemic events: results from the asymptomatic carotid stenosis and risk of stroke study.
      recently concluded that morphologic assessment of plaque structure may allow the identification of a subgroup of asymptomatic carotid stenoses with a 4.5-fold increase in the risk of developing ipsilateral neurologic symptoms compared with those with a similar degree of stenosis, which will reduce the number of patients requiring intervention to prevent one stroke. At present, however, this type of plaque analysis
      • Biasi G.M.
      • Froio A.
      • Diethrich E.B.
      • Deleo G.
      • Galimberti S.
      • Mingazzini P.
      • et al.
      Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) Study.
      • Nicolaides A.N.
      • Kakkos S.K.
      • Griffin M.
      • Sabetai M.
      • Dhanjil S.
      • Thomas D.J.
      • et al.
      Effect of image normalization on carotid plaque classification and the risk of ipsilateral hemispheric ischemic events: results from the asymptomatic carotid stenosis and risk of stroke study.
      is not widely available and requires further prospective evaluation to determine its ultimate clinical utility.
      The imaging modalities most often used to evaluate patients for cervical carotid stenosis are carotid DUS (CDUS), magnetic resonance imaging (MRI) and angiography (MRA), computed tomography angiography (CTA), and digital subtraction angiography (DSA). Each of these will be discussed in turn.

      Carotid duplex ultrasound imaging

      DUS imaging provides an accurate and reliable noninvasive tool to determine the degree of cervical carotid stenosis and plaque morphology in most patients. It is usually the initial study in patients who present with symptoms or a carotid bruit. Because the study is highly dependent on technique, testing should be done in an accredited vascular laboratory (eg, Intersocietal Commission for the Accreditation of Vascular Laboratories), and the images should be reviewed by physicians experienced in vascular ultrasound interpretation.
      Determining the degree of carotid artery stenosis is largely based on an analysis of the peak systolic velocity (PSV) or the end-diastolic velocity (EDV), or both, of the carotid artery. A panel of experts from several medical specialties convened in October 2002 in San Francisco, California, under the auspices of the Society of Radiologists in Ultrasound, to arrive at a consensus regarding the performance of Doppler US imaging to aid in the diagnosis of ICA stenosis.
      • Grant E.G.
      • Benson C.B.
      • Moneta G.L.
      • Alexandrov A.V.
      • Baker J.D.
      • Bluth E.I.
      • et al.
      Carotid artery stenosis: grayscale and Doppler ultrasound diagnosis – Society of Radiologists in Ultrasound Consensus Conference.
      This panel of experts recommended a cutoff PSV of the ICA of ≥125 cm/s for predicting angiographic >50% stenosis and ≥230 cm/s for predicting >70% ICA stenosis. These recommended criteria are based on an analysis of several published studies and the experience of the panelists rather than values validated against other imaging modalities.
      AbuRahma et al
      • AbuRahma A.F.
      • Srivastava M.
      • Stone P.A.
      • Mousa A.Y.
      • Jain A.
      • Dean L.S.
      • et al.
      Critical appraisal of the carotid duplex consensus criteria in the diagnosis of carotid artery stenosis.
      recently analyzed the CDUS and angiography results of 376 carotid arteries in their institution. Using the consensus criteria, they demonstrated a sensitivity of 93%, specificity of 68%, and overall accuracy of 85% for stenosis between 50% and 69%. A PSV of ≥230 cm/s for ≥70% stenosis had a sensitivity of 99%, specificity of 86%, and overall accuracy of 95%. Receiver operator curves showed that the ICA PSV was significantly better than EDV or ICA/CCA ratio (P = .036) in detecting ≥70% stenosis and ≥50% stenosis. There was no improvement in accuracy by adding the EDV values or the ratios, or both, to the PSV values.
      Velocity-based estimation of carotid artery stenosis may need to be adjusted in certain circumstances, for example, higher velocities in women than in men and higher velocities in the presence of contralateral carotid artery occlusion.
      • Comerota A.J.
      • Salles-Cunha S.X.
      • Daoud Y.
      • Jones L.
      • Beebe H.G.
      Gender differences in blood velocities across carotid stenoses.
      • Busuttil S.J.
      • Franklin D.P.
      • Youkey J.R.
      • Elmore J.R.
      Carotid duplex overestimation of stenosis due to severe contralateral disease.
      High carotid bifurcation, severe arterial tortuosity, extensive vascular calcification, and obesity may also reduce the accuracy of DUS imaging. Carotid stents will decrease compliance of the vessel wall and flow velocity.
      • Lal B.K.
      • Hobson R.W.
      • Tofghi B.
      • Kapadia I.
      • Cuadra S.
      • Jamil Z.
      Duplex ultrasound velocity criteria for the stented carotid artery.
      DUS imaging may also fail to differentiate between subtotal and total carotid occlusion. Intravenous administration of contrast agents may improve diagnostic accuracy,
      • Sitzer M.
      • Rose G.
      • Fürst G.
      • Siebler M.
      • Steinmetz H.
      Characteristics and clinical value of an intravenous echo-enhancement agent in evaluation of high-grade internal carotid stenosis.
      • Ferrer J.M.
      • Samsó J.J.
      • Serrando J.R.
      • Valenzuela V.F.
      • Montoya S.B.
      • Docampo M.M.
      Use of ultrasound contrast in the diagnosis of carotid artery occlusion.
      but the safety of these agents has been questioned.
      Power Doppler and contrast DUS imaging can be used to differentiate between preocclusive stenosis and complete occlusion.
      • Bude R.O.
      • Rubin J.M.
      • Adler R.S.
      Power versus conventional color Doppler sonography: comparison in the depiction of normal intrarenal vasculature.
      Overall, each vascular laboratory should have in place an internal validation process of their own criteria for their internal use.
      DUS imaging of the carotid artery has two major limitations: quality dependence on the technician's examination and limitations of visualization of the proximal carotid artery and intracranial portions. Although the intracranial cerebral arteries can be assessed with transcranial Doppler imaging, this technique is not as widely available at most institutions as other imaging modalities.
      In addition to determining percent stenosis, DUS, as noted above, has been used to determine plaque characteristics (echogenicity) using gray scale median values, which predict the stroke risk of a particular plaque. Plaque characterization is not routine in every vascular laboratory and requires specific protocols to assure standardization of results.

      Magnetic resonance imaging and angiography

      MRA has the advantage of being noninvasive, does not require iodinated contrast or ionizing radiation, and provides an unlimited number of projections of the carotid lumen from a single acquisition. MRA can also assess intrathoracic and intracranial lesions that are not amenable to DUS interrogation. MRA does not visualize the surrounding soft tissue structures, unless additional MRI is performed, and calcium within the plaque is not defined. It cannot be used in patients with implanted ferromagnetic devices, such as implantable defibrillators and pacemakers, and is of limited use in uncooperative patients and those with claustrophobia. The gadolinium-based compounds used as a contrast agent for MRA have been associated with nephrogenic systemic fibrosis in patients with pre-existing renal disorders.
      • Nederkoom P.J.
      • van der Graaf Y.
      • Hunink M.G.
      Duplex ultrasound and magnetic resonance angiography compared with digital subtraction angiography in carotid artery stenosis: a systematic review.
      MRA has a tendency to overestimate the degree of carotid stenosis. The sensitivity and specificity for diagnosing 70% to 99% stenosis with time-of-flight MRA are identical to DUS imaging (88% and 84%, respectively); however, MRA has a tendency to “over-read” stenosis, making it difficult to differentiate more moderate (50% to 69%) from severe stenosis. Similarly, high-grade stenosis will result in a loss of signal on MRA. This does not represent a carotid occlusion when the more distal cervical carotid is visualized. However, when there is no reconstitution of the cervical carotid artery on MRA, the diagnosis of carotid occlusion can be made with a high degree of certainty.
      • Nederkoom P.J.
      • van der Graaf Y.
      • Hunink M.G.
      Duplex ultrasound and magnetic resonance angiography compared with digital subtraction angiography in carotid artery stenosis: a systematic review.
      • Remonda L.
      • Senn P.
      • Barth A.
      • Arnold M.
      • Lövblad K.O.
      • Schroth G.
      Contrast-enhanced 3D MR angiography of the carotid artery: comparison with conventional digital subtraction angiography.
      MRI can be used to analyze plaque morphology, specifically the structure of the atherosclerotic plaque. It can identify the lipid-rich necrotic core and the fibrous capsule with high sensitivity and specificity
      • Yuan C.
      • Mitsumori L.M.
      • Ferguson M.S.
      • Polissar N.L.
      • Echelard D.
      • Ortiz G.
      • et al.
      In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques.
      and can distinguish between an intact thick, thin, or ruptured fibrous cap.
      • Hatsukami T.S.
      • Ross R.
      • Polissar N.L.
      • Yuan C.
      Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging.
      When dedicated protocols are used, MR also can demonstrate specific plaque components, including calcium, lipid, fibrocellular element, or thrombus within the plaques.

      Computed tomography angiography

      CTA is less susceptible than MRA to overestimating the severity of carotid stenosis. The rapid acquisition of spiral CT images allows excellent timing with contrast administration and provides quality images that can be viewed in multiple planes. CTA is extremely fast and offers submillimeter spatial resolution (0.3 vs 0.8 mm for contrast-enhanced MRA), is less expensive than contrast-enhanced MRA, provides a faster processing time, and can visualize soft tissue, bone, and blood vessels at the same time. CTA can also demonstrate vascular anomalies, has the ability to quantify the extent of calcification, and can interrogate the arterial tree from the aortic arch to the circle of Willis. Stenoses can be measured with electronic microcalipers based on NASCET or ECST methods.
      • Bartlett E.S.
      • Walters T.D.
      • Symons S.P.
      • Fox A.J.
      Quantification of carotid stenosis on CT angiography.
      A meta-analysis of 28 studies analyzing the diagnostic accuracy of CTA compared with DSA showed a pooled sensitivity of 85% and specificity of 93% for CTA in detecting 70% to 99% carotid stenosis and a sensitivity and specificity for occlusions of 97% and 99%.
      • Koelemay M.J.
      • Nederkoorn P.J.
      • Reitsma J.B.
      • Majoie C.B.
      Systematic review of computed tomographic angiography for assessment of carotid artery disease.
      CTA was also highly accurate in identifying calcification but less reliable in describing carotid plaque morphology, specifically the lipid component, or ulceration. CTA appears less reliable than DUS imaging or MRA for assessing plaque morphology.
      • Grønholdt M.L.
      B-mode ultrasound and spiral CT for the assessment of carotid atherosclerosis.
      Other limitations of this technique include cost (compared with DUS), contrast exposure, and the added concern of radiation exposure. In addition, a large calcium burden can limit the ability to distinguish contrast from calcium during postprocessing imaging.

      Catheter-based DSA

      Many authorities still consider carotid conventional digital angiography to be the gold standard against all other imaging modalities in patients with extracranial cerebrovascular disease. Measurement of carotid stenosis using DSA is generally done using the NASCET method.
      North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET)
      Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      Conventional angiography is generally reserved for patients with conflicting imaging studies before CEA or in patients considered for CAS. DSA provides high-quality imaging that is accurate, objective, and easy to interpret. It can identify lesions from the aortic arch to the intracranial vessels. Major limitations of angiography that make it inappropriate as a screening modality include its cost and associated risks, specifically of stroke.
      • Hankey G.J.
      • Warlow C.P.
      • Molyneux A.J.
      Complications of cerebral angiography for patients with mild carotid territory ischaemia being considered for carotid endarterectomy.
      • Davies K.N.
      • Humphrey P.R.
      Complications of cerebral angiography in patients with symptomatic carotid territory ischaemia screened by carotid ultrasound.
      • Leonardi M.
      • Cenni P.
      • Simonetti L.
      • Raffi L.
      • Battaglia S.
      Retrospective study of complications arising during cerebral and spinal diagnostic angiography from 1998 to 2003.
      Overall, DSA is most useful in patients when less invasive imaging studies produce conflicting results. When DUS imaging is equivocal, DSA is preferred over CT and MR in evaluating patients with renal dysfunction (by minimizing contrast load), obesity, or in-dwelling ferromagnetic material, which render CTA or MRA technically inadequate or difficult.

      Comparison of CDUS, MRA, CTA, and DSA

      The U.K. Health Technology Assessment concluded that although contrast-enhanced MRA was the most accurate imaging modality overall, it was limited by unavailability, inaccessibility, and delays. Therefore, they concluded that color DUS imaging remained the preferred imaging modality for identifying patients with 70% to 99% stenosis.
      • Wardlaw J.M.
      • Chappell F.M.
      • Stevenson M.
      • De Nigris E.
      • Thomas S.
      • Gillard J.
      • et al.
      Accurate, practical and cost-effective assessment of carotid stenosis in the UK.
      As such, CDUS is the preferred imaging modality for the identification of asymptomatic stenosis.
      This recommendation was based on several factors, including low cost, a much higher number of strokes likely to be prevented in the long-term by the rapid availability of CDUS imaging in contrast with other imaging, and the good sensitivity of imaging in detecting significant stenosis. However, the Health Technology Assessment highlighted the concern of the accuracy of DUS in diagnosing 50% to 69% stenosis, which carries a sensitivity of only 36% and a specificity of 91%.
      • Wardlaw J.M.
      • Chappell F.M.
      • Stevenson M.
      • De Nigris E.
      • Thomas S.
      • Gillard J.
      • et al.
      Accurate, practical and cost-effective assessment of carotid stenosis in the UK.
      The utility of CDUS will depend on the clinical presentation of the patient. In neurologically symptomatic patients, a diagnosis by CDUS of stenosis between 50% and 69% is sufficient to proceed with surgery based on its specificity. However, a negative CDUS result would mandate another imaging study because of the low sensitivity of CDUS in this setting. In neurologically asymptomatic patients, a moderate stenosis (50% to 69%) diagnosed by CDUS should be confirmed by another imaging study before intervention is undertaken.

      Imaging after carotid intervention

      The prevalence of carotid artery restenosis after CEA varies between 1% and 37%,
      • Sadideen H.
      • Taylor P.R.
      • Padayachee T.S.
      Restenosis after carotid endarterectomy.
      • Moore W.S.
      • Kempczinski R.F.
      • Nelson J.J.
      • Toole J.F.
      Recurrent carotid stenosis: results of the Asymptomatic Carotid Atherosclerosis Study.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      Eversion versus conventional carotid endarterectomy: late results of a prospective multicenter randomized trial.
      • Sundt Jr, T.M.
      • Whisnant J.P.
      • Houser O.W.
      • Fode N.C.
      Prospective study of the effectiveness and durability of carotid endarterectomy.
      although symptomatic recurrent stenoses is infrequent (0% to 8%).
      • Sadideen H.
      • Taylor P.R.
      • Padayachee T.S.
      Restenosis after carotid endarterectomy.
      Factors associated with restenosis include continued smoking, small ICA diameter, operative defect detected at intraoperative assessment, and primary closure after CEA. The aggregate incidence of residual and recurrent carotid stenosis after CEA in ACAS was 13%.
      • Moore W.S.
      • Kempczinski R.F.
      • Nelson J.J.
      • Toole J.F.
      Recurrent carotid stenosis: results of the Asymptomatic Carotid Atherosclerosis Study.
      Of 136 patients who had restenosis, 8 (5.9%) underwent reoperation, only 1 of whom was symptomatic. There was no correlation between late stroke and recurrent stenosis. Similarly, Cao et al
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      Eversion versus conventional carotid endarterectomy: late results of a prospective multicenter randomized trial.
      randomized 1353 patients who underwent CEA. Of these, the eversion technique was used in 678, and standard CEA with primary closure was done in 419 and patch closure in 256. The life-table estimate of the cumulative risk of restenosis at 4 years was 4% in the eversion CEA group and 9% in the standard CEA group, and 98% of these patients were asymptomatic.
      Several studies have reported the progression of contralateral stenosis after CEA.
      • Raman K.G.
      • Layne S.
      • Makaroun M.S.
      • Kelley M.E.
      • Rhee R.Y.
      • Tzeng E.
      • et al.
      Disease progression in contralateral carotid artery is common after endarterectomy.
      • Martin-Conejero A.
      • Reina-Gutierrez T.
      • Serrano-Hernando F.J.
      • Sanchez-Hervas L.
      • Blanco-Cañibano E.
      • Ponce-Cano A.I.
      • et al.
      Disease progression in the contralateral carotid artery after endarterectomy.
      • AbuRahma A.F.
      • Robinson P.A.
      • Mullins D.A.
      • Holt S.M.
      • Herzog T.A.
      • Mowery N.T.
      Frequency of postoperative carotid duplex surveillance and type of closure: results from randomized trial.
      Contralateral carotid stenosis progression was more frequent than ipsilateral recurrent stenosis during the long-term follow-up in these studies. These studies also identified that the risk of contralateral carotid artery stenosis progression depends on the existing disease at the time of the initial CEA.
      • Raman K.G.
      • Layne S.
      • Makaroun M.S.
      • Kelley M.E.
      • Rhee R.Y.
      • Tzeng E.
      • et al.
      Disease progression in contralateral carotid artery is common after endarterectomy.
      • Martin-Conejero A.
      • Reina-Gutierrez T.
      • Serrano-Hernando F.J.
      • Sanchez-Hervas L.
      • Blanco-Cañibano E.
      • Ponce-Cano A.I.
      • et al.
      Disease progression in the contralateral carotid artery after endarterectomy.
      • AbuRahma A.F.
      • Robinson P.A.
      • Mullins D.A.
      • Holt S.M.
      • Herzog T.A.
      • Mowery N.T.
      Frequency of postoperative carotid duplex surveillance and type of closure: results from randomized trial.
      The risk of progression for moderate stenosis at the initial surveillance to severe stenosis can be as high as five times.
      • Martin-Conejero A.
      • Reina-Gutierrez T.
      • Serrano-Hernando F.J.
      • Sanchez-Hervas L.
      • Blanco-Cañibano E.
      • Ponce-Cano A.I.
      • et al.
      Disease progression in the contralateral carotid artery after endarterectomy.
      Several large prospective studies
      • Yadav J.S.
      • Wholey M.H.
      • Kuntz R.E.
      • Fayad P.
      • Katzen B.T.
      • Mishkel G.J.
      • et al.
      Protected carotid-artery stenting versus endarterectomy in high-risk patients.
      • Chakhtoura E.Y.
      • Hobson 2nd, R.W.
      • Goldstein J.
      • Simonian G.T.
      • Lal B.K.
      • Haser P.B.
      • et al.
      In-stent restenosis after carotid angioplasty-stenting: incidence and management.
      • Roubin G.S.
      • New G.
      • Iyer S.S.
      • Vitek J.J.
      • Al-Mubarak N.
      • Liu M.W.
      • et al.
      Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery stenosis: a 5-year prospective analysis.
      • Wholey M.H.
      • Al-Mubarek N.
      • Wholey M.H.
      Updated review of the global carotid artery stent registry.
      • McCabe D.J.
      • Pereira A.C.
      • Clifton A.
      • Bland J.M.
      • Brown M.M.
      CAVATAS Investigators
      Restenosis after carotid angioplasty, stenting, or endarterectomy in the carotid and vertebral artery transluminal angioplasty study (CAVATAS).
      • AbuRahma A.F.
      • Abu-Halimah S.
      • Bensenhaver J.
      • Dean L.S.
      • Keiffer T.
      • Emmett M.
      • et al.
      Optimal carotid duplex velocity criteria for defining the severity of carotid in-stent restenosis.
      have analyzed the rate of carotid in-stent restenosis after CAS. More patients had >70% stenosis of the ipsilateral carotid artery 1 year after CAS than after CEA (19% vs 5%). Use of CDUS to diagnose post-CAS restenosis is confounded by changes in the velocity criterion caused by the stent itself, and standard diagnostic criteria do not apply. Artifacts associated with both CTA and MRA similarly limit the utility of these techniques in the post-CAS patient. DSA is required to confirm restenosis after CAS identified by CDUS when reintervention is contemplated. In contrast, CDUS is sufficient to diagnose and plan therapy for restenosis after CEA.
      • Recommendations for selection of carotid imaging modalities
      • 1
        CDUS in an accredited vascular laboratory is the initial diagnostic imaging of choice for evaluating the severity of stenosis in symptomatic and asymptomatic patients. Unequivocal identification of stenosis of 50% to 99% in neurologically symptomatic patients or 70% to 99% in asymptomatic patients is sufficient to make a decision regarding intervention (GRADE 1, Level of Evidence A).
      • 2
        CDUS in an accredited vascular laboratory is the imaging modality of choice to screen asymptomatic populations at high risk (GRADE 1, Level of Evidence B).
      • 3
        When CDUS is nondiagnostic or suggests stenosis of intermediate severity (50% to 69%) in an asymptomatic patient, additional imaging with MRA, CTA or DSA is required before embarking on any intervention (GRADE 1, Level of Evidence B).
      • 4
        When evaluation of the vessels proximal or distal to the cervical carotid arteries is needed for diagnosis or to plan therapy, imaging with CTA, MRA, or catheter angiography in addition to CDUS is indicated. CTA is preferable to MRI or MRA for delineating calcium. When there is discordance between two minimally invasive imaging studies (CDUS, MRA, CTA), DSA is indicated to resolve conflicting results. DSA is generally reserved for situations where there is inconclusive evidence of stenosis on less invasive studies or when CAS is planned (GRADE 1, Level of Evidence B).
      • 5
        A postoperative DUS study ≤30 days is recommended to assess the status of the endarterectomized vessel. In patients with ≥50% stenosis on this study, further follow-up imaging to assess progression or resolution is indicated. In patients with a normal DUS study result and primary closure of the endarterectomy site, ongoing imaging is recommended to identify recurrent stenosis. In patients with a normal DUS after patch or eversion endarterectomy, further imaging of the endarterectomized vessel may be indicated if the patient has multiple risk factors for progression of atherosclerosis. There are insufficient data to make recommendations on imaging after CAS (GRADE 2, Level of Evidence C). Although the data in this area are not robust concerning intervals for follow-up imaging, the committee was unanimous in this recommendation, recognizing that follow-up DUS carries little risk.
      • 6
        Imaging after CAS or CEA is indicated to monitor contralateral disease progression in patients with contralateral stenosis ≥50%. In patients with multiple risk factors for vascular disease, follow-up DUS may be indicated with lesser degrees of stenosis. The likelihood of disease progression is related to the initial severity of stenosis (GRADE 2, Level of Evidence C). Although the data in this area are not robust concerning intervals for follow-up imaging, the committee was unanimous in this recommendation, recognizing that follow-up DUS carries little risk.

      III. Medical management of patients with carotid stenosis

      Optimal medical management is an important part of overall treatment of all patients with carotid bifurcation disease, regardless of the degree of stenosis or the plan for intervention. This therapy is directed both at the reduction of stroke and overall cardiovascular events, including cardiovascular-related mortality. The best medical management for stroke prevention was highlighted in clinical practice guidelines issued jointly in 2006 by the AHA and the American Stroke Association, and cosponsored by the Council on Cardiovascular Radiology and Intervention and the American Academy of Neurology.
      • Sacco R.L.
      • Adams R.
      • Albers G.
      • Alberts M.J.
      • Benavente O.
      • Furie K.
      • et al.
      Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.

      Treatment of hypertension

      Elevated blood pressure increases the risk for stroke,
      • Rodgers A.
      • MacMahon S.
      • Gamble G.
      • Slattery J.
      • Sandercock P.
      • Warlow C.
      Blood pressure and risk of stroke in patients with cerebrovascular disease. The United Kingdom Transient Ischaemic Attack Collaborative Group.
      and reducing blood pressure decreases the risk for stroke.
      • Lawes C.M.
      • Bennett D.A.
      • Feigin V.L.
      • Rodgers A.
      Blood pressure and stroke: an overview of published reviews.
      The relationship between blood pressure and stroke risk is “continuous, consistent, and independent of other risk factors.”
      • Chobanian A.V.
      • Bakris G.L.
      • Black H.R.
      • Cushman W.C.
      • Green L.A.
      • Izzo Jr, J.L.
      • et al.
      The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.
      The Framingham Heart study,
      • Wilson P.W.
      • Hoeg J.M.
      • D'Agostino R.B.
      • Silbershatz H.
      • Belanger A.M.
      • Poehlmann H.
      • et al.
      Cumulative effects of high cholesterol levels, high blood pressure, and cigarette smoking on carotid stenosis.
      the Atherosclerosis Risk in Communities (ARIC) study,
      • Heiss G.
      • Sharrett A.R.
      • Barnes R.
      • Chambless L.E.
      • Szklo M.
      • Alzola C.
      Carotid atherosclerosis measured by B-mode ultrasound in populations: associations with cardiovascular risk factors in the ARIC study.
      and the Cardiovascular Health Study
      • Howard G.
      • Manolio T.A.
      • Burke G.L.
      • Wolfson S.K.
      • O'Leary D.H.
      Does the association of risk factors and atherosclerosis change with age? An analysis of the combined ARIC and CHS cohorts. The Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) investigators.
      each found that hypertension was independently associated with an elevated risk for carotid artery atherosclerosis. Each 10-mm Hg increase in blood pressure results in an increase in risk for stroke of 30% to 45%. Each 10-mm Hg reduction in blood pressure amongst hypertensive patients decreases the risk for stroke by 33%.
      • Lawes C.M.
      • Bennett D.A.
      • Feigin V.L.
      • Rodgers A.
      Blood pressure and stroke: an overview of published reviews.
      Lowering blood pressure to a target <140/90 mm Hg by lifestyle interventions and antihypertensive treatment is recommended in individuals who have hypertension with asymptomatic carotid atherosclerosis.
      • Sacco R.L.
      • Adams R.
      • Albers G.
      • Alberts M.J.
      • Benavente O.
      • Furie K.
      • et al.
      Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.
      Aggressive lowering of blood pressure may harm patients who have had a recent stroke by reducing cerebral perfusion. In fact, the Joint National Committee for the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure-VII has remained ambiguous regarding recommendations for antihypertensive management in patients with a recent stroke.
      • Chobanian A.V.
      • Bakris G.L.
      • Black H.R.
      • Cushman W.C.
      • Green L.A.
      • Izzo Jr, J.L.
      • et al.
      The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.
      However, antihypertensive therapy aimed at reducing blood pressures to <140/90 is recommended for patients who have had an ischemic stroke or TIA and are beyond the hyperacute period.
      • Sacco R.L.
      • Adams R.
      • Albers G.
      • Alberts M.J.
      • Benavente O.
      • Furie K.
      • et al.
      Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.

      Treatment of diabetes mellitus

      In the Cardiovascular Health Study, an elevated fasting glucose level was associated with an increased risk for stroke in patients with carotid atherosclerosis.
      • Smith N.L.
      • Barzilay J.I.
      • Shaffer D.
      • Savage P.J.
      • Heckbert S.R.
      • Kuller L.H.
      • et al.
      Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study.
      The Insulin Resistance Atherosclerosis Study
      • Wagenknecht L.E.
      • D'Agostino Jr, R.
      • Savage P.J.
      • O'Leary D.H.
      • Saad M.F.
      • Haffner S.M.
      Duration of diabetes and carotid wall thickness. The Insulin Resistance Atherosclerosis Study (IRAS).
      and the Atherosclerosis Risk in the Community study
      • Dobs A.S.
      • Nieto F.J.
      • Szklo M.
      • Barnes R.
      • Sharrett A.R.
      • Ko W.J.
      Risk factors for popliteal and carotid wall thicknesses in the Atherosclerosis Risk in Communities (ARIC) Study.
      showed that diabetes was associated with intima-media thickness of the carotid artery and with progression in intima-media thickness. The United Kingdom Prospective Diabetes Study (UKPDS),
      • Laakso M.
      Benefits of strict glucose and blood pressure control in type 2 diabetes: lessons from the UK Prospective Diabetes Study.
      the Action to Control Cardiovascular Risk in Diabetes (ACCORD)
      • Gerstein H.C.
      • Miller M.E.
      • Byington R.P.
      • Goff Jr, D.C.
      • Bigger J.T.
      • et al.
      Action to Control Cardiovascular Risk in Diabetes Study Group
      Effects of intensive glucose lowering in type 2 diabetes.
      study, and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE)
      • Patel A.
      • MacMahon S.
      • Chalmers J.
      • Neal B.
      • Billot L.
      • Woodward M.
      • et al.
      The ADVANCE Collaborative Group
      Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
      trial all tested whether tight control of serum glucose levels in diabetic patients would reduce the risk for stroke. Despite achieving hemoglobin A1C levels <6.5%, no reduction in stroke risk was identified in these trials. Glucose control to nearly normoglycemic levels (target hemoglobin A1C <7%) is recommended among diabetic patients to reduce microvascular complications and, with lesser certainty, macrovascular complications other than stroke.

      Treatment of lipid abnormalities

      The relationship between elevated cholesterol and incident MI in patients with coronary artery atherosclerosis is well established; however, the relationship between hypercholesterolemia and incident stroke is less clear. A meta-analysis of 45 studies of strokes in patients with hypercholesterolemia did not suggest an increased risk for stroke in patients with elevated serum cholesterol.
      Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS).
      However, several other prospective studies in men and women have subsequently identified an increase in incident stroke associated with elevated cholesterol levels.
      • Iso H.
      • Jacobs Jr, D.R.
      • Wentworth D.
      • Neaton J.D.
      • Cohen J.D.
      Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial.
      • Bots M.L.
      • Elwood P.C.
      • Nikitin Y.
      • Salonen J.T.
      • Freire de Concalves A.
      • Inzitari D.
      • et al.
      Total and HDL cholesterol and risk of stroke. EUROSTROKE: a collaborative study among research centres in Europe.
      • Horenstein R.B.
      • Smith D.E.
      • Mosca L.
      Cholesterol predicts stroke mortality in the women's Pooling Project.
      Patients with known atherosclerosis have demonstrated reduced stroke rates when treated with lipid-lowering therapy. The Multiple Risk Factor Intervention Trial of statin therapy in hypercholesterolemic patients observed that greater reductions in levels of low-density lipoprotein (LDL) were associated with a reduction in stroke risk. A meta-analysis of 26 trials observed that the risk of stroke decreased by >15% for every 10% reduction in serum LDL
      • Baigent C.
      • Keech A.
      • Kearney P.M.
      • Blackwell L.
      • Buck G.
      • Pollicino C.
      • et al.
      Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
      in patients with known coronary or other atherosclerosis.
      Further meta-analyses of statin trials that also reported on stroke as an outcome have shown that statin therapy reduces the risk of stroke by 15% to 30%.
      • Bucher H.C.
      • Griffith L.E.
      • Guyatt G.H.
      Effect of HMGCoA Reductase Inhibitors on stroke A meta-analysis of randomized, controlled trials.
      The Stroke Prevention by Aggressive Reduction in Cholesterol trial found that atorvastatin treatment of patients with a recent stroke or TIA resulted in a reduction in stroke rate by 16% over 5 years.
      • Amarenco P.
      • Goldstein L.B.
      • Szarek M.
      • Sillesen H.
      • Rudolph A.E.
      • Callahan 3rd, A.
      • et al.
      Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in cholesterol Levels (SPARCL) trial.
      It is less clear if aggressive lipid-lowering therapy results in regression of carotid artery atherosclerosis. Aggressive statin therapy in the Measuring Effects on Intima-Media Thickness: an Evaluation of Rosuvastatin study,
      • Crouse 3rd, J.R.
      • Grobbee D.E.
      • O'Leary D.H.
      • Bots M.L.
      • Evans G.W.
      • Palmer M.K.
      • et al.
      Measuring Effects on intima media Thickness: an Evaluation Of Rosuvastatin in subclinical atherosclerosis–the rationale and methodology of the METEOR study.
      the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol
      • Taylor A.J.
      • Kent S.M.
      • Flaherty P.J.
      • Coyle L.C.
      • Markwood T.T.
      • Vernalis M.N.
      ARBITER: Arterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol: a randomized trial comparing the effects of atorvastatin and pravastatin on carotid intima medial thickness.
      study, and the Atorvastatin vs Simvastatin on Atherosclerosis Progression
      • Smilde T.J.
      • van Wissen S.
      • Wollersheim H.
      • Trip M.D.
      • Kastelein J.J.
      • Stalenhoef A.F.
      Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): a prospective, randomised, double-blind trial.
      study all showed increased regression of the carotid artery intima-media thickness compared with controls.
      Although LDL is the primary determinant of cardiovascular and stroke risk, low levels of high-density lipoprotein (HDL) cholesterol also influence stroke risk, and elevation of HDL has been shown to reduce the risk of stroke.
      National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
      Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood cholesterol in Adults (Adult Treatment Panel III) final report.
      In an analysis of a large (>9200) series of patients, treated by dual therapy aimed at decreasing LDL and raising HDL, elevation of HDL level was independently associated with a reduction of stroke risk by a factor of 0.86. Conversely, an elevated total cholesterol/HDL ratio increased stroke risk by a factor of 1.22. Reducing cholesterol absorption has also been shown to reduce stroke risk in patients with familial hypercholesterolemia.
      • van den Bogaard B.
      • van den Born B.J.
      • Fayyad R.
      • Waters D.D.
      • DeMicco D.A.
      • LaRosa J.C.
      • et al.
      On-treatment lipoprotein components and risk of cerebrovascular events in the Treating to New Targets study.
      Overall, however, the HDL level had much less effect on stroke risk than did the level of LDL.
      Elevated cholesterol, comorbid CAD, or evidence of an atherosclerotic etiology of carotid stenosis should be managed according to National Cholesterol Education Program-Adult Treatment Panel III guidelines,
      • Avellone G.
      • Di Garbo V.
      • Guarnotta V.
      • Scaglione R.
      • Parrinello G.
      • Purpura L.
      • et al.
      Efficacy and safety of long-term ezetimibe/simvastatin treatment in patients with familial hypercholesterolemia.
      which include lifestyle modification or medications, or both. Statin agents are recommended targeting LDL of 100 mg/dL, for those with coronary heart disease or symptomatic atherosclerotic disease, and LDL of 70 mg/dL for very high-risk persons with multiple risk factors.

      Smoking cessation

      Smoking nearly doubles the risk of stroke.
      • Shinton R.
      • Beevers G.
      Meta-analysis of relation between cigarette smoking and stroke.
      • Wolf P.A.
      • D'Agostino R.B.
      • Kannel W.B.
      • Bonita R.
      • Belanger A.J.
      Cigarette smoking as a risk factor for stroke. The Framingham study.
      Smoking also acts synergistically on other risk factors that are known to increase the risk of stroke, such as CAD and PAD. Conversely, smoking cessation results in a reduction in risk for CAD and for coronary mortality.
      • Gordon T.
      • Kannel W.B.
      • McGee D.
      • Dawber T.R.
      Death and coronary attacks in men after giving up cigarette smoking A report from the Framingham Study.
      Cessation also reduces the risk of stroke in men and women.
      • Gordon T.
      • Kannel W.B.
      • McGee D.
      • Dawber T.R.
      Death and coronary attacks in men after giving up cigarette smoking A report from the Framingham Study.
      • Kawachi I.
      • Colditz G.A.
      • Stampfer M.J.
      • Willett W.C.
      • Manson J.E.
      • Rosner B.
      • et al.
      Smoking cessation and decreased risk of stroke in women.
      • Wannamethee S.G.
      • Shaper A.G.
      • Whincup P.H.
      • Walker M.
      Smoking cessation and the risk of stroke in middle-aged men.
      Counseling and smoking cessation medications are effective in helping smokers to quit. Physician counseling is an important and effective intervention that reduces smoking in patients by 10% to 20%
      • Fiore M.C.
      • Bailey W.C.
      • Cohen S.J.
      • et al.
      Smoking cessation Clinical Practice Guideline No.
      but continues to be underused.
      • Frank E.
      • Winkleby M.A.
      • Altman D.G.
      • Rockhill B.
      • Fortmann S.P.
      Predictors of physician's smoking cessation advice.
      Nicotine replacement therapy, in the form of patches and gums, is effective in reducing smoking.
      • Fiore M.C.
      • Smith S.S.
      • Jorenby D.E.
      • Baker T.B.
      The effectiveness of the nicotine patch for smoking cessation A meta-analysis.
      Patients with extracranial carotid stenosis who are smoking cigarettes should be counseled to quit.

      Antithrombotic treatment

      No adequately powered studies have been performed in asymptomatic patients with carotid atherosclerosis to confirm a benefit with antithrombotic treatment in reducing incident stroke. The US Preventative Services Task Force has recommended daily aspirin as cardiovascular prophylaxis in patients with anticipated cardiac morbidity of >3% for men aged >45 years and in women aged >55 years.
      • Wolff T.
      • Miller T.
      • Ko S.
      Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force.
      These recommendations are based primarily on an observed reduction in overall cardiovascular morbidity and death with aspirin therapy. The AHA Primary Prevention of Cardiovascular Disease and Stroke agrees with this recommendation.
      • Pearson T.A.
      • Blair S.N.
      • Daniels S.R.
      • Eckel R.H.
      • Fair J.M.
      • Fortmann S.P.
      • et al.
      AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients without Coronary or other atherosclerotic Vascular Diseases American Heart Association Science Advisory and Coordinating Committee.
      There is no evidence to suggest that antiplatelet agents other than aspirin have improved benefit in asymptomatic patients with carotid atherosclerosis.
      Evidence for antithrombotic treatment for secondary prevention of recurrent stroke in symptomatic patients with carotid atherosclerosis is more robust.
      • Sacco R.L.
      • Adams R.
      • Albers G.
      • Alberts M.J.
      • Benavente O.
      • Furie K.
      • et al.
      Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.
      Antithrombotic Trialists' Collaboration
      Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
      • Albers G.W.
      • Amarenco P.
      • Easton J.D.
      • Sacco R.L.
      • Teal P.
      • et al.
      Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
      • Wolf P.A.
      • Clagett G.P.
      • Easton J.D.
      • Goldstein L.B.
      • Gorelick P.B.
      • Kelly-Hayes M.
      • et al.
      Preventing ischemic stroke in patients with prior stroke and transient ischemic attack: a statement for healthcare professionals from the Stroke Council of the American Heart Association.
      • Johnston S.C.
      • Nguyen-Huynh M.N.
      • Schwarz M.E.
      • Fuller K.
      • Williams C.E.
      • Josephson S.A.
      • et al.
      National Stroke Association guidelines for the management of transient ischemic attacks.
      The choice of antiplatelet therapy among aspirin, clopidogrel, and dipyridamole plus aspirin is not clearly defined because the data are uncertain.
      The Clopidogrel in Unstable Angina to Prevent Recurrent Events
      • Fox K.A.
      • Mehta S.R.
      • Peters R.
      • Zhao F.
      • Lakkis N.
      • Gersh B.J.
      • et al.
      Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST segment elevation acute coronary syndrome: the clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) trial.
      and Clopidogrel for the Reduction of Events During Observation
      • Steinhubl S.R.
      • Berger P.B.
      • Mann 3rd, J.T.
      • Fry E.T.
      • DeLago A.
      • Wilmer C.
      • et al.
      Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial.
      trials each showed a benefit of clopidogrel plus aspirin compared with aspirin alone in reducing vascular events in patients with prior acute coronary syndromes. The Management of Atherothrombosis with Clopidogrel in High-risk Patients
      • Diener H.C.
      • Bogousslavsky J.
      • Brass L.M.
      • Cimminiello C.
      • Csiba L.
      • Kaste M.
      • et al.
      Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial.
      subsequently demonstrated no significant difference in vascular events between symptomatic patients with carotid stenosis treated with clopidogrel plus aspirin compared with clopidogrel alone.
      Clopidogrel alone was initially shown to have a small advantage over aspirin in this subset of patients in the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events
      CAPRIE Steering Committee
      A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE).
      trial. However, it costs more than aspirin, and the subsequent Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance
      • Bhatt D.L.
      • Fox K.A.
      • Hacke W.
      • Berger P.B.
      • Black H.R.
      • Boden W.E.
      • et al.
      Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.
      trial showed that clopidogrel plus aspirin was equivalent to aspirin alone in preventing vascular events in patients with a prior stroke, TIA, or other cardiovascular disease or in patients with high risk for cardiovascular disease.
      Antiplatelet agents are therefore recommended for patients with non-cardioembolic ischemic stroke or TIA associated with carotid atherosclerosis. Aspirin (50-325 mg/d), the combination of aspirin and extended-release dipyridamole, and clopidogrel, are all acceptable options for initial therapy; a combination of aspirin and clopidogrel is not recommended.
      Aspirin is currently the most commonly used antiplatelet agent and one of the most frequently prescribed drugs, with as many as 30 million Americans on long-term aspirin regimens. A growing body of evidence suggests that some patients compliant with aspirin therapy may still develop atherothrombotic complications, such as stroke. Reduced antiaggregant effect is more common in patients taking lower-dose aspirin (81 mg) or 325 mg aspirin with an enteric coating than it is in patients taking 325 mg of noncoated aspirin daily.
      • Alberts M.J.
      • Bergman D.L.
      • Molner E.
      • Jovanovic B.D.
      • Ushiwata I.
      • Teruya J.
      Antiplatelet effect of aspirin in patients with with cerebrovascular disease.
      The lack of consensus for the definition of aspirin resistance and for the specific laboratory test to identify it has led to large variability in its reported prevalence.
      • Kasotakis G.
      • Pipinos I.I.
      • Lynch T.G.
      Current evidence and clinical implications of aspirin resistance.
      The routine laboratory evaluation of platelet reactivity is not justifiable. The pharmacologic response to clopidogrel also demonstrates significant interindividual variability.
      Patients with reduced platelet inhibition in response to clopidogrel appear to be at increased risk for cardiovascular events. This resistance may result from reduced bioavailability, polymorphisms of cytochrome P450, additional genetic variants, or increased platelet turnover.
      • Mega J.L.
      • Close S.L.
      • Wiviott S.D.
      • Shen L.
      • Hockett R.D.
      • Brandt J.T.
      • et al.
      Cytochrome p-450 polymorphisms in response to clopidogrel.
      Prasugrel is an alternate platelet-inhibiting pharmacologic agent of the same class as clopidogrel that does not have these limitations. It has been approved for use in acute coronary syndromes,
      • Wiviott S.D.
      • Braunwald E.
      • McCabe C.H.
      • Montalescot G.
      • Ruzyllo W.
      • Gottlieb S.
      • et al.
      Prasugrel versus clopidogrel in patients with acute coronary syndromes.
      but no data are available on its use for stroke prevention.
      As in the case of aspirin resistance, current evidence does not suggest the routine use of platelet function or genetic testing for clopidogrel resistance. In the absence of randomized trial data, the general approach to patients developing clinical events while taking aspirin or clopidogrel has been to confirm compliance and increase the dosage, followed by the addition or substitution of another antiplatelet agent.
      • De Miguel A.
      • Ibanez B.
      • Badimón J.J.
      Clinical implications of clopidogrel resistance.
      However, data in this area are insufficient to allow clear recommendations.

      Anticoagulant therapy

      Parenteral and oral anticoagulants are effective in the prevention of embolic stroke in patients with atrial fibrillation or prosthetic heart valves. However, warfarin anticoagulation has been shown to be less effective than antiplatelet therapy for secondary prevention of neurologic events in patients with carotid atherosclerosis who do not have a history of atrial fibrillation and is not indicated in patients with symptoms of cerebral ischemia.
      • Mohr J.P.
      • Thompson J.L.
      • Lazar R.M.
      • Levin B.
      • Sacco R.L.
      • Furie K.L.
      • et al.
      A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.
      • Halkes P.H.
      • van Gijn J.
      • Kappelle L.J.
      • Koudstaal P.J.
      • Algra A.
      ESPRIT Study Group
      Medium intensity anticoagulation vs. aspirin after cerebral ischemia or arterial origin (ESPRIT): a randomized controlled trial.
      The Warfarin-Aspirin Reduced Cardiac Ejection Fraction Study trial is currently investigating the potential advantage in preventing cardioembolic stroke of anticoagulation vs aspirin in patients with chronic congestive heart failure.
      • Nair A.
      • Sealove B.
      • Halperin J.L.
      • Webber G.
      • Fuster V.
      Anticoagulation in patients with heart failure: who, when, and why?.

      Medical management for the perioperative period of CEA

      Hypertension is a common comorbidity in patients undergoing CEA. Blood pressure fluctuations, both above and below normal, are a significant source of morbidity and may contribute to MI and postoperative reperfusion syndrome. Careful periprocedural blood pressure management is critical to obtaining optimal results from the operation. Although the most recent AHA guidelines do not classify CEA as a high-risk surgical procedure mandating β-blockade, they do indicate that all patients with known CAD should receive β-blockade therapy before CEA to achieve a stable blood pressure and heart rate of 60 to 80 beats/min.
      • Fleisher L.A.
      • Beckman J.A.
      • Brown K.A.
      • Calkins H.
      • Chaikof E.L.
      • Fleischmann K.E.
      • et al.
      ACC/AHA 2007 Guidelines on Perioperative cardiovascular Evaluation and care for Noncardiac Surgery: a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery.
      American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines; American Society of Echocardiography; American Society of Nuclear Cardiology; Heart Rhythm Society; Society of Cardiovascular Anesthesiologists; Society for Cardiovascular Angiography and Interventions
      2009 ACCF/AHA focused update on perioperative beta blockade incorporated into the ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery.
      Given the near ubiquity of this condition in patients with carotid stenosis, β-blockade is nearly universally required in this patient group.
      Patients taking combined aspirin and clopidogrel therapy in the perioperative period have a 0.4% to 1.0% higher risk of major bleeding compared with aspirin alone.
      • Eikelboom J.W.
      • Hirsh J.
      Bleeding and management of bleeding.
      Aspirin therapy alone does not have to be discontinued before CEA.
      • Merritt J.C.
      • Bhatt D.L.
      The efficacy and safety of perioperative antiplatelet therapy.
      The risks of periprocedural MI from aspirin withdrawal outweigh the risk of fatal or severe bleeding from aspirin use. The ACC Perioperative Guidelines endorses the continued use of aspirin before and after CEA.
      • Fleisher L.A.
      • Beckman J.A.
      • Brown K.A.
      • Calkins H.
      • Chaikof E.L.
      • Fleischmann K.E.
      • et al.
      ACC/AHA 2007 Guidelines on Perioperative cardiovascular Evaluation and care for Noncardiac Surgery: a Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery.
      A low dose (81 to 325 mg) appears at least as effective as higher doses, and higher doses may in fact be less effective.

      Stone DH, Goodney PP, Schanzer A, Nolan BW, Adams JE, Powell RJ, et al. Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery. J Vasc Surg 2011[E-pub ahead of print: doi:10.1016/j.jvs.2011.03.003].

      Patients should continue aspirin therapy after CEA indefinitely, according to recommendations for high-risk patients with atherosclerosis.
      • Sacco R.L.
      • Adams R.
      • Albers G.
      • Alberts M.J.
      • Benavente O.
      • Furie K.
      • et al.
      Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: the American Academy of Neurology affirms the value of this guideline.
      Antithrombotic Trialists' Collaboration
      Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
      • Albers G.W.
      • Amarenco P.
      • Easton J.D.
      • Sacco R.L.
      • Teal P.
      • et al.
      Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
      • Wolf P.A.
      • Clagett G.P.
      • Easton J.D.
      • Goldstein L.B.
      • Gorelick P.B.
      • Kelly-Hayes M.
      • et al.
      Preventing ischemic stroke in patients with prior stroke and transient ischemic attack: a statement for healthcare professionals from the Stroke Council of the American Heart Association.
      • Johnston S.C.
      • Nguyen-Huynh M.N.
      • Schwarz M.E.
      • Fuller K.
      • Williams C.E.
      • Josephson S.A.
      • et al.
      National Stroke Association guidelines for the management of transient ischemic attacks.
      There has been a consensus that preprocedural clopidogrel should be stopped approximately 5 days before elective CABG.
      • Eagle K.A.
      • Guyton R.A.
      • Davidoff R.
      • Edwards F.H.
      • Ewy G.A.
      • Gardner T.J.
      • et al.
      ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to update the 1999 guidelines for coronary artery bypass graft surgery).
      Recent data from a large, retrospective, multicentered clinical experience
      • Taylor D.W.
      • Barnett H.J.
      • Haynes R.B.
      • Ferguson G.G.
      • Sackett D.L.
      • Thorpe K.E.
      • et al.
      Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial ASA and Carotid Endarterectomy (ACE) Trial Collaborators.
      suggest that clopidogrel may be safely continued through the perioperative period without increased bleeding risk. It is therefore reasonable to individualize the management of perioperative clopidogrel therapy. There is no clear information regarding the risks or benefits of continued clopidogrel monotherapy in the periprocedural period for CEA.
      One meta-analysis showed preoperative statin therapy resulted in a significant reduction in perioperative mortality in patients undergoing vascular surgery.
      • Hindler K.
      • Shaw A.D.
      • Samuels J.
      • Fulton S.
      • Collard C.D.
      • Riedel B.
      Improved postoperative outcomes associated with preoperative statin therapy.
      One small randomized trial found that perioperative death, MI, and stroke in patients undergoing vascular surgery was reduced in the group treated with atorvastatin.
      • Durazzo A.E.
      • Machado F.S.
      • Ikeoka D.T.
      • De Bernoche C.
      • Monachini M.C.
      • Puech-Leão P.
      • et al.
      Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial.
      In one large observational study of hospital records of 780,591 patients undergoing noncardiac surgery, the risk-adjusted mortality rate was significantly lower in those who received perioperative statins than in those who were not taking statins (odds ratio, 0.62; 95% confidence interval [CI], 0.58-0.67).
      • Lindenauer P.K.
      • Pekow P.
      • Wang K.
      • Gutierrez B.
      • Benjamin E.M.
      Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery.
      The evidence for continued use of statin therapy currently remains largely observational. Furthermore, the optimal time for starting therapy, the duration of therapy, dose, or target LDL levels to be achieved still remain to be determined.

      Medical management for the perioperative period of CAS

      Antihypertensive, β-blocker, and lipid-lowering therapy should be initiated in patients undergoing CAS according to the same recommendations for CEA. Patients should be started on dual antiplatelet therapy with aspirin (325 mg) and clopidogrel (75 mg) or ticlopidine (250 mg). No randomized trial has yet compared CAS performed with dual-antiplatelet therapy vs aspirin alone. However, the published periprocedural stroke, MI, and death rates in all recent clinical trials have been achieved with this combination therapy.
      • Brott T.G.
      • Hobson 2nd, R.W.
      • Howard G.
      • Roubin G.S.
      • Clark W.M.
      • Brooks W.
      • et al.
      Stenting versus endarterectomy for treatment of carotid-artery stenosis.
      • Ederle J.
      • Dobson J.
      • Featherstone R.L.
      • Bonati L.H.
      • van der Worp H.B.
      • et al.
      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.
      • Mas J.L.
      • Chatellier G.
      • Beyssen B.
      • Branchereau A.
      • Moulin T.
      • Becquemin J.P.
      • et al.
      Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis.
      • Massop D.
      • Dave R.
      • Metzger C.
      • Bachinsky W.
      • Solis M.
      • Shah R.
      • et al.
      Stenting and angioplasty with protection in patients at high-risk for endarterectomy: SAPPHIRE Worldwide Registry first 2,001 patients.
      Dual-antiplatelet therapy should be continued for 1 month after the procedure, and aspirin should be continued indefinitely.
      • Recommendations for medical management of patients with carotid atherosclerosis
      • 1
        In patients with carotid artery stenosis, treatment of hypertension, hypercholesterolemia, and efforts at smoking cessation are recommended to reduce overall cardiovascular risk and risk of stroke regardless of whether intervention is planned. Targets are those defined by the National Cholesterol Education Program guidelines (GRADE 1, Level of Evidence A).
      • 2
        Aggressive treatment of hypertension in the setting of acute stroke is not recommended; however, treatment of hypertension after this period has passed is associated with reduced risk of subsequent stroke. The target parameters are not well defined (GRADE 1, Level of Evidence C).
      • 3
        Treatment of diabetes with the goal of tight glucose control has not been shown to reduce stroke risk or decrease complication rates after CEA and is not recommended for these purposes (GRADE 2, Level of Evidence A).
      • 4
        Anticoagulation is not recommended for the treatment of TIA or acute stroke, unless there is evidence of a cardioembolic source (GRADE 1, Level of Evidence B).
      • 5
        Antiplatelet therapy in asymptomatic patients with carotid atherosclerosis is recommended to reduce overall cardiovascular morbidity, although it has not been shown to be effective in the primary prevention of stroke (GRADE 1, Level of Evidence A).
      • 6
        Antiplatelet therapy is recommended for secondary stroke prevention: aspirin, aspirin combined with dipyridamole, and clopidogrel are all effective. Clopidogrel combined with aspirin is not more effective than either drug alone (GRADE 1, Level of Evidence B).
      • 7
        Perioperative medical management of patients undergoing carotid revascularization should include blood pressure control (<140/80 mm Hg), β-blockade (heart rate, 60-80 beats/min), and statin therapy (LDL <100 mg/dL) (GRADE 1, Level of Evidence B).
      • 8
        Perioperative antithrombotic therapy for CEA should include aspirin (81-325 mg) (GRADE 1, Level of Evidence A). The use of clopidogrel in the perioperative period should be decided case-by-case (GRADE 2 Level of Evidence B).
      • 9
        Perioperative antithrombotic management of CAS patients should include dual-antiplatelet therapy with aspirin and ticlopidine or clopidogrel. Dual-antiplatelet therapy should be initiated at least 3 days before CAS and continued for 1 month, and aspirin therapy should be continued indefinitely (GRADE 1, Level of Evidence C).

      IV. Technical recommendations for carotid interventions

      The efficacy of carotid interventions depends on minimizing perioperative complication rates. This involves appropriate risk factor assessment and patient selection, perioperative therapy, and performance of a technically excellent operation. Perioperative therapy and medical management have been discussed in the previous sections. Specific recommendations on techniques to reduce complications of CEA and CAS are beyond the scope of this report and can be found elsewhere.
      • Momin T.A.
      • Ricotta J.J.
      Minimizing the Complications of Carotid Endarterectomy.
      • Parodi F.E.
      • Schonholz C.
      • Parodi J.C.
      Minimizing Complications of Carotid stenting.
      However, some general recommendations can be made regarding the conduct of CEA and CAS.

      Carotid endarterectomy

      Among the variables that have been studied to determine their effect on the outcome of CEA are local vs regional anesthesia, routine vs selective use of shunts, monitoring of brain function during the procedure, routine patch closure after endarterectomy, and completion imaging. Although several authors have suggested that use of regional or local anesthesia is associated with a reduced incidence of perioperative hemodynamic changes and cardiac events, a prospective randomized trial
      • Lewis S.C.
      • Warlow C.P.
      • Bodenham A.R.
      • Colam B.
      • Rothwell P.M.
      • et al.
      GALA Trial Collaborative Group
      General anaesthesia versus local anaesthesia for carotid surgery (GALA): a multicentre, randomized controlled trial.
      and systematic review of the literature
      • Rerkasem K.
      • Rothwell P.M.
      The Cochrane Collaboration
      Local versus general anesthesia for carotid endarterectomy (Review).
      failed to show any difference between the two anesthetic approaches.
      An abundant literature exists on the indications identifying patients at risk of flow-related ischemia during CEA and the role of shunting in reducing this complication. Factors associated with increased risk of cerebral ischemia during carotid cross-clamping, and therefore the increased likelihood that a shunt will be needed, during CEA, include recent stroke, contralateral carotid occlusion, and symptoms suggestive of hemodynamic cerebral insufficiency.
      • Ballotta E.
      • Saladini M.
      • Gruppo M.
      • Mazzalai F.
      • Da Giau G.
      • Baracchini C.
      Predictors of electroencephalographic changes needing shunting during carotid endarterectomy.
      • Skelly C.L.
      • Meyerson S.L.
      • Curi M.A.
      • Desai T.R.
      • Bassiouny H.S.
      • McKinsey J.F.
      • et al.
      Routine early postoperative duplex scanning is unnecessary following uncomplicated carotid endarterectomy.
      Despite extensive study on the routine or selective use of shunts and cerebral monitoring during CEA, no clear benefit of one approach over the other has emerged.
      • Bond R.
      • Rerkasem K.
      • Counsell C.
      • Salinas R.
      • Naylor R.
      • Warlow C.P.
      • et al.
      Routine or selective carotid artery shunting for carotid endarterectomy (and different methods of monitoring in selective shunting).
      The routine use of completion imaging after CEA also remains an area of controversy. Although a number of authors have reported detecting abnormalities in 5% to 10% of patients using completion DUS imaging,
      • Bandyk D.F.
      • Mills J.L.
      • Gahtan V.
      • Esses G.E.
      Intraoperative Duplex scanning of arterial reconstructions: fate of repaired and unrepaired defects.
      • Ascher E.
      • Markevich N.
      • Kallakuri S.
      • Schutzer R.W.
      • Hingorani A.P.
      Intraoperative carotid artery duplex scanning in a modern series of 650 consecutive primary endarterectomy procedures.
      and a cost-benefit analysis suggests completion DUS imaging increases quality-adjusted life-years by 2%,
      • Burnett M.G.
      • Stein S.C.
      • Sonnad S.S.
      • Zager E.L.
      Cost-effectiveness of intraoperative imaging in carotid endarterectomy.
      the clinical significance of many of these abnormalities is uncertain, and several series have reported excellent results without use of completion imaging.
      • O'Brien-Irr R.J.
      Completion angiography, is it really necessary?.
      • Rockman C.B.
      • Halm E.A.
      Intraoperative imaging: does it really improve perioperative outcomes of carotid endarterectomy?.
      • Chiriano J.
      • Abou-Zamzam Jr, A.M.
      • Molkara N.K.
      • Zhang W.W.
      • Bianchi C.
      • Teruya T.H.
      Preoperative carotid duplex findings predict carotid stump pressures during endarterectomy in symptomatic but not asymptomatic patients.
      Like the choice of anesthesia and shunting, completion imaging remains a matter of personal preference.
      There are, however, data to recommend the use of patch angioplasty or eversion endarterectomy over standard endarterectomy with primary closure. Women and individuals with small ICAs are at most risk of early neurologic events and late restenosis if standard endarterectomy with primary closure is performed. Randomized studies have shown the benefit of patch closure over primary closure in patients undergoing standard CEA.
      • Bond R.
      • Rerkasem K.
      • Naylor A.R.
      • Aburahma A.F.
      • Rothwell P.M.
      Systematic Review of randomized controlled trials of patch angioplasty versus primary closure and different types of patch materials during carotid endarterectomy.
      The type of patch material does not appear to have a significant effect on outcome. Prospective comparisons of eversion CEA with primary closure
      • Cao P.
      • De Rango P.
      • Zannetti S.
      Eversion vs. conventional carotid endarterectomy: a systematic review.
      have demonstrated a benefit of the eversion technique for reduction of early and late stroke. This has been borne out by low rates of early stroke and late restenosis in large single-center reports.
      • Darling 3rd, R.C.
      • Mehta M.
      • Roddy S.P.
      • Paty P.S.
      • Kreienberg P.B.
      • Ozsvath K.J.
      • et al.
      Eversion carotid endarterectomy: a technical alternative that may obviate patch closure in women.
      A number of investigations have studied the relationship of operative volume and specialty training with outcome. Although data suggest that there is some relationship between operative volume and outcome, the effect appears less than with other procedures.
      • Matsen S.L.
      • Chang D.C.
      • Perler B.A.
      • Roseborough G.S.
      • Williams G.M.
      Trends in the in-hospital stroke rate following carotid endarterectomy in California and Maryland.
      In a large study of Medicare populations in Maryland and California, surgeons who perform 10 to 15 CEAs per year have better results than those who perform <5 procedures annually, but there was no added benefit to performing more than this relatively low threshold. There has been no consistent relationship between surgical specialty and outcome, and any effect seen is likely related to volume rather than specialty designation.
      • Cowan J.A.
      • Dimick J.B.
      • Thompson B.C.
      • Stanley J.A.
      • Upchurch G.R.
      Surgeon volume as an indicator of outcomes after carotid endarterectomy: an effect independent of specialty practice and hospital volume.
      • Matsen S.L.
      • Chang D.C.
      • Perler B.A.
      • Roseborough G.S.
      • Williams G.M.
      Trends in the in-hospital stroke rate following carotid endarterectomy in California and Maryland.
      • AbuRahma A.F.
      • Robinson P.
      Indications and complications of carotid endarterectomy as performed by four different surgical specialty groups.

      Carotid artery stenting

      The periprocedural management of the CAS patient has been discussed in a previous section. Periprocedural antiplatelet therapy is mandatory, and appropriate attention to access vessels and the status of the aortic arch is required for optimal results. The technical conduct of the CAS involves access of the target vessel, crossing the target lesion, and stent deployment. Technical issues related to carotid stenting include achieving a stable platform for the procedure, use of embolic protection devices, stent dilation before deployment, stent selection, and postdeployment dilation.
      Stable sheath access in the proximal CCA is required. This depends on appropriate patient selection, as described above. Once a stable platform is obtained, a decision must be made about use of a cerebral protection device. In general, cerebral protection device deployment has been suggested to reduce the incidence of distal embolization and, potentially, the risk of stroke.
      • Garg N.
      • Karagiorgos N.
      • Pisimisis G.T.
      • Sohal D.P.
      • Longo G.M.
      • Johanning J.M.
      • et al.
      Cerebral protection devices reduce periprocedural strokes during carotid angioplasty and stenting: a systematic review of the current literature.
      • Vos J.A.
      • van den Berg J.C.
      • Ernst S.M.
      • Suttorp M.J.
      • Overtoom T.T.
      • Mauser H.W.
      • et al.
      Carotid angioplasty and stent placement: comparison of transcranial Doppler US data and clinical outcome with and without filtering cerebral protection devices in 509 patients.
      Although this position is not supported by robust data, it has been generally accepted by the medical community, and use of an embolic protection device has been required by Centers for Medicare and Medicaid Services to qualify for reimbursement.
      Several embolic protection devices are available, and selection depends on lesion characteristics and anatomic considerations. Options include proximal or distal occlusion devices designed to interrupt forward flow during the procedure and filter devices placed distal to the lesion designed to trap debris released during the procedure. Distal occlusion devices have the advantage of a smaller diameter than proximal occlusion devices, but the lesion must be crossed before the device is placed in the ICA, a maneuver that can itself cause embolization. At the end of the procedure, suction is applied between the sheath in the CCA and the balloon occluding the distal internal carotid artery to remove debris.
      Proximal occlusion devices require placement of two occlusion balloons, one each in the common and external carotid artery, with flow reversal by suction or creation of a proximal arteriovenous connection.
      • Parodi J.C.
      • Schönholz C.
      • Parodi F.E.
      • Sicard G.
      • Ferreira L.M.
      Initial 200 cases of carotid artery stenting using a reversal of flow cerebral protection device.
      Placement of a proximal occlusion device avoids crossing the lesion before protection is in place and has been associated with the lowest incidence of distal embolization as detected by transcranial Doppler imaging or postoperative MRI.
      • Parodi J.C.
      • Schönholz C.
      • Parodi F.E.
      • Sicard G.
      • Ferreira L.M.
      Initial 200 cases of carotid artery stenting using a reversal of flow cerebral protection device.
      • Schnaudigel S.
      • Gröschel K.
      • Pilgram S.M.
      • Kastrup A.
      New brain lesions after carotid stenting versus carotid endarterectomy: a systematic review of the literature.
      • Ansel G.M.
      • Hopkins L.N.
      • Jaff M.R.
      • Rubino P.
      • Bacharach J.M.
      • Scheinert D.
      • Myla S.
      • et al.
      Safety and efficacy of the INVATEC MOMA proximal cerebral protection device during carotid artery stenting: results form the ARMOUR pivotal trial.
      The main procedural disadvantages of the current proximal occlusion devices are the relatively large size (9F) of the access sheath, the need to occlude both the common and external carotid artery, and the need to establish venous access for continuous flow reversal. Proximal and distal occlusion devices may both be problematic in patients with poor intracranial collateral circulation because they mandate cessation—and sometimes reversal—of antegrade flow in the ICA. This situation is generally encountered in ≤5% of patients and may be managed by short intermittent inflation times.
      Distal filters are deployed in the distal ICA and trap debris released during angioplasty and stent deployment. Like distal occlusion devices, they have the advantage of a smaller diameter (6F), but the lesion must be initially crossed in an unprotected fashion. These filters come in a variety of configurations and pore sizes. Their efficacy is related to the degree with which they can reliably achieve complete apposition to the distal arterial wall. They have the advantage that antegrade ICA flow can be maintained throughout the procedure; however, the filter may become completely occluded if large amounts of debris are released, and debris may escape distally during filter recapture.
      The choice of filter device is often related to individual preference and familiarity. Some authors believe proximal occlusion with flow reversal is preferable in nearly all circumstances; however, this technique has its greatest advantage in lesions with a high risk of embolization (markedly irregular plaque, echolucent lesions, active symptoms) or in those that may be difficult to cross due to tortuosity or severe narrowing because protection is in place before the lesion is manipulated. Use of a filter over proximal or distal occlusion is preferred if there is a likelihood that interruption of antegrade ICA flow will not be tolerated. Distal occlusion devices are preferred to filters when the distal ICA anatomy suggests that compete apposition of filter to the distal ICA wall may be difficult due to size or tortuosity.
      Direct comparison of proximal occlusion with flow reversal vs distal protection shows that proximal protection with flow reversal results in the lowest embolic load
      • Parodi F.E.
      • Schonholz C.
      • Parodi J.C.
      Minimizing Complications of Carotid stenting.
      • Schnaudigel S.
      • Gröschel K.
      • Pilgram S.M.
      • Kastrup A.
      New brain lesions after carotid stenting versus carotid endarterectomy: a systematic review of the literature.
      However, no device can completely eliminate the risk of embolization during CAS. The fact that no embolic protection is completely effective and that some emboli originate during cannulation of the aortic arch and the proximal great vessels suggests that although improvements to embolization after CAS can be made, the problem cannot be eliminated.
      Studies using postoperative diffusion-weighted MRI shown increased 17% incidence of MRI-identified infarcts in patients undergoing CAS compared with CEA (adjusted risk ratio, 5.21).
      • Ederle J.
      • Dobson J.
      • Featherstone R.L.
      • Bonati L.H.
      • van der Worp H.B.
      • et al.
      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.
      Although these are generally subclinical, recent reports suggest these lesions might be associated with subtle long-term neurologic changes. Echolucent lesions are more likely to be associated with increased embolic risk, whereas recurrent stenoses or fibrous lesions are associated with a decreased risk of procedural embolization.
      • Biasi G.M.
      • Froio A.
      • Diethrich E.B.
      • Deleo G.
      • Galimberti S.
      • Mingazzini P.
      • et al.
      Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) Study.
      • Roubin G.S.
      • New G.
      • Iyer S.S.
      • Vitek J.J.
      • Al-Mubarak N.
      • Liu M.W.
      • et al.
      Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery stenosis: a 5-year prospective analysis.
      • Parodi F.E.
      • Schonholz C.
      • Parodi J.C.
      Minimizing Complications of Carotid stenting.
      • Parodi J.C.
      • Schönholz C.
      • Parodi F.E.
      • Sicard G.
      • Ferreira L.M.
      Initial 200 cases of carotid artery stenting using a reversal of flow cerebral protection device.
      Stent predilation is not recommended unless a filter cannot be passed. Stent selection is often based on physician preference. The only large study to test the effect of cell size suggests that closed-cell stents more effectively constrain the carotid plaque and reduce embolization,
      • Hart J.P.
      • Peeters P.
      • Verbist J.
      • Deloose K.
      • Bosiers M.
      Do device characteristics impact outcome in carotid artery stenting?.
      but there is no consensus on that point. Open-cell stents are more conformable than closed-cell stents and are preferred by some in tortuous anatomy. Once the stent has been deployed, postdilation is used to ensure stent apposition to the plaque, but vigorous postdilation to achieve anatomic perfection is avoided.
      The learning curve associated with CAS has been the object of considerable study. The Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis
      • Mas J.L.
      • Chatellier G.
      • Beyssen B.
      • Branchereau A.
      • Moulin T.
      • Becquemin J.P.
      • et al.
      Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis.
      (EVA-3S) study was criticized because of the requirement that interventionalists perform only 25 procedures to qualify for participation in the trial. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) study required a significant lead-in phase for interventionalists and documentation of low procedural morbidity.
      • Hopkins L.N.
      • Roubin G.S.
      • Chakhtoura E.Y.
      • Gray W.A.
      • Ferguson R.D.
      • Katzen B.T.
      • et al.
      The Carotid revascularization Endarterectomy versus stenting trial: credentialing of interventionalists and final results of the lead-in phase.
      • Hobson 2nd, R.W.
      • Howard V.J.
      • Roubin G.S.
      • Ferguson R.D.
      • Brott T.G.
      • Howard G.
      • et al.
      Credentialing of Surgeons as interventionalists for carotid artery stenting: experience from the lead-in phase of CREST.
      It is worth noting that CREST is associated with the lowest periprocedural complication rate in the literature. There are data in the literature that suggest achieving a low predictable complication rate after CAS requires a higher level of initial and ongoing experience than current guidelines suggest.
      • Wholey M.H.
      • Al-Mubarek N.
      • Wholey M.H.
      Updated review of the global carotid artery stent registry.
      • Verzini F.
      • De Rango P.
      • Parlani G.
      • Panuccio G.
      • Cao P.
      Carotid artery stenting: technical issues and role of operator's experience.
      • Lin P.H.
      • Bush R.L.
      • Peden E.K.
      • Zhou W.
      • Guerrero M.
      • Henao E.A.
      • et al.
      Carotid artery stenting with neuroprotection: assessing the learning curve and treatment outcome.
      No relationship has been demonstrated between specialty and outcome. Data from CREST demonstrate that vascular surgeons, cardiologists, interventional radiologists, and interventional neurologists can all achieve comparable results with CAS and that experience is more important than specialty designation in assuring optimal outcomes.
      • Hopkins L.N.
      • Roubin G.S.
      • Chakhtoura E.Y.
      • Gray W.A.
      • Ferguson R.D.
      • Katzen B.T.
      • et al.
      The Carotid revascularization Endarterectomy versus stenting trial: credentialing of interventionalists and final results of the lead-in phase.
      • Hobson 2nd, R.W.
      • Howard V.J.
      • Roubin G.S.
      • Ferguson R.D.
      • Brott T.G.
      • Howard G.
      • et al.
      Credentialing of Surgeons as interventionalists for carotid artery stenting: experience from the lead-in phase of CREST.
      • Recommendations regarding CEA and CAS technique
      • 1
        Patch angioplasty or eversion endarterectomy are recommended rather than primary closure to reduce the early and late complications of CEA (GRADE 1, Level of Evidence A).
      • 2
        Use of an embolic protection device (proximal or distal occlusion, distal filter) is recommended during CAS to reduce the risk of cerebral embolization (GRADE 1, Level of Evidence B).

      V. Selecting the appropriate therapy: Medical management, CAS, or CEA

      Once a patient with a clinically significant carotid stenosis is identified, appropriate treatment must be selected. Treatment is primarily directed at the reduction of stroke risk. The risks of an interventional treatment must be considered when treatment choices are made. In general, rates of stroke, MI, and death have been used when comparing CAS with CEA. In most clinical trials comparing CAS with CEA, stroke, MI, and death have been given equal weight in determining a composite end point to test overall efficacy.
      Data from CREST,
      • Brott T.G.
      • Hobson 2nd, R.W.
      • Howard G.
      • Roubin G.S.
      • Clark W.M.
      • Brooks W.
      • et al.
      Stenting versus endarterectomy for treatment of carotid-artery stenosis.
      however, indicate that stroke has a more significant effect on quality of life at 1 year than nonfatal MI. Because the primary goal of intervention in carotid stenosis is stroke prevention, in developing its recommendations, the committee placed more emphasis on the prevention of stroke and procedurally related death than the occurrence of periprocedural MI. This may result in committee recommendations that differ from the published results of some trials where these three end points were given equal weight in analysis.
      Treatment is chosen based on the assessment of risk associated with intervention and the likelihood that a particular intervention will favorably alter the course of the disease. The major determinants of the clinical course of patients with carotid bifurcation stenosis are the presence or absence of neurologic symptoms and the degree of carotid bifurcation stenosis. The threat of stroke in asymptomatic patients with <60% ICA stenosis and in symptomatic patients with 50% stenosis is generally considered to be small and does not warrant intervention. ECST and NASCET
      North American Symptomatic Carotid Endarterectomy Trial Collaborators (NASCET)
      Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      • Barnett H.J.
      • Taylor D.W.
      • Eliasziw M.
      • Fox A.J.
      • Ferguson G.G.
      • Haynes R.B.
      • et al.
      Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
      Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST).
      demonstrated that CEA was unable to reduce the subsequent neurologic event rates in patients with symptoms of cerebral ischemia and bifurcation stenosis of <50% diameter reduction and was actually associated with increased morbidity compared with medical management. Stenoses of <60% diameter reduction were excluded from the asymptomatic studies,
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      assuming that asymptomatic patients with stenosis <60% would not benefit from carotid reconstruction. Given the findings of the symptomatic trials, this proved to be an appropriate decision. There have been no studies supporting either CEA or CAS for this cohort of patients.
      • Chambers B.R.
      • Donnan G.A.
      Carotid endarterectomy for asymptomatic carotid stenosis.

      Assessing the risk associated with intervention

      CEA and CAS are each associated with specific clinical scenarios that increase their respective risks. This section provides information to identify conditions that pose an increased risk for CAS or CEA and thereby help select the most appropriate therapy. When the risk of intervention is sufficiently increased due to the presence of one or more of these factors, medical therapy may be more appropriate than CEA or CAS.
      In the initial CAS trials, a series of anatomic and physiologic criteria were developed by a consensus panel in an attempt to identify “high-risk” CEA patients who might be expected to benefit from CAS.
      • Ricotta 2nd, J.J.
      • Malgor R.D.
      A review of the trials comparing carotid endarterectomy and carotid angioplasty and stenting.
      Although these criteria were used to enroll patients in CAS trials and registries, their ability to define “high risk” was never validated in a prospective manner. In fact, some have suggested that CEA could be safely performed in most of these patients.
      • Mozes G.
      • Sullivan T.M.
      • Torres-Russotto D.R.
      • Bower T.C.
      • Hoskin T.L.
      • Sampaio S.M.
      • et al.
      Carotid endarterectomy in SAPPHIRE-eligible high-risk patients: implications for selecting patients for carotid angioplasty and stenting.
      • Gasparis A.P.
      • Ricotta L.
      • Cuadra S.A.
      • Char D.J.
      • Purtill W.A.
      • van Bemmelen P.S.
      • et al.
      High-risk carotid endarterectomy (CEA): facts or fiction.
      As CAS experience matured, certain conditions have been shown to be associated with increased complications after CAS. Risk stratification can generally be divided into two categories: anatomic (including the lesion) characteristics and physiologic characteristics.

       1. Anatomic and lesion characteristics

       a. Lesion location

      CEA provides excellent access to the cervical carotid artery, but lesions that extend outside this zone can be difficult to treat surgically. Lesions at or above the level of the C2 cervical vertebra or below the clavicle are generally more difficult to expose surgically for CEA without increasing the morbidity of the operation. Lesions of the distal cervical carotid artery can be exposed by division of the digastric muscle and subluxation or division of the mandible, as required.
      • Simonian G.T.
      • Pappas P.J.
      • Padberg Jr, F.T.
      • Samit A.
      • Silva Jr, M.B.
      • Jamil Z.
      • et al.
      Mandibular subluxation for distal internal carotid exposure: technical considerations.
      • Jaspers G.W.
      • Witjes M.J.
      • van den Dungen J.J.
      • Reintsema H.
      • Zeebregts C.J.
      Mandibular subluxation for distal internal carotid artery exposure in edentulous patients.
      Although rarely required, these high carotid exposures may be associated with increased difficulty in directly visualizing the end point of the endarterectomy and with increased incidence of cranial nerve injury, particularly cranial nerve IX.
      • Simonian G.T.
      • Pappas P.J.
      • Padberg Jr, F.T.
      • Samit A.
      • Silva Jr, M.B.
      • Jamil Z.
      • et al.
      Mandibular subluxation for distal internal carotid exposure: technical considerations.
      • Jaspers G.W.
      • Witjes M.J.
      • van den Dungen J.J.
      • Reintsema H.
      • Zeebregts C.J.
      Mandibular subluxation for distal internal carotid artery exposure in edentulous patients.
      Lesions of the very proximal CCAs are difficult or impossible to expose without extending the incision into the chest. This must be considered when evaluating the morbidity of the procedure.

       b. Lesion characteristics

      Lesion-specific characteristics are thought to increase the risk of cerebral vascular events after CAS
      • Biasi G.M.
      • Froio A.
      • Diethrich E.B.
      • Deleo G.
      • Galimberti S.
      • Mingazzini P.
      • et al.
      Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) Study.
      • Setacci C.
      • Chisci E.
      • Setacci F.
      • Iacoponi F.
      • de Donato G.
      • Rossi A.
      Siena carotid artery stenting score: a risk modeling study for individual patients.
      and include a “soft” lipid-rich plaque identified on noninvasive imaging, extensive (15 mm or more) disease, a preocclusive lesion, and circumferential heavy calcification. A recent publication using multivariate logistic regression analysis of a large patient cohort demonstrated increased periprocedural stroke risk (odds ratios, 2.5-5.6) among patients with lesions >15 mm, excessive calcification, and ulceration.
      • Setacci C.
      • Chisci E.
      • Setacci F.
      • Iacoponi F.
      • de Donato G.
      • Rossi A.
      Siena carotid artery stenting score: a risk modeling study for individual patients.
      An earlier study has shown a periprocedural stroke risk (odds ratio, 7.1) among patients with a lipid-rich plaque treated with CAS.
      • Biasi G.M.
      • Froio A.
      • Diethrich E.B.
      • Deleo G.
      • Galimberti S.
      • Mingazzini P.
      • et al.
      Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk of Stroke (ICAROS) Study.
      The CAS procedure requires manipulation of a wire and a self-expanding stent through the carotid lesion. Unstable plaque increases the risk of embolization during placement of the wire or stent across the carotid lesion. This can be reduced, but not eliminated, by using flow-reversal embolic protection rather than distal filter protection.
      • Schnaudigel S.
      • Gröschel K.
      • Pilgram S.M.
      • Kastrup A.
      New brain lesions after carotid stenting versus carotid endarterectomy: a systematic review of the literature.
      Long segment lesions may require the placement of multiple stents, and this situation and preocclusive stenoses are both associated with a higher risk of acute or late stent occlusion. Heavy circumferential calcification makes lesion dilation more difficult and also increases the risk of embolization with CAS. There are no lesion specific characteristics that increase the risk of CEA.

       c. Other anatomic considerations

      Several anatomic situations may increase the difficulty of CEA. These include reoperation after prior CEA, existence of a cervical stoma, history of neck radiotherapy with resultant local fibrotic changes of the skin and soft tissues, and previous ablative neck surgery, such as radical neck dissection and laryngectomy.
      • Mozes G.
      • Sullivan T.M.
      • Torres-Russotto D.R.
      • Bower T.C.
      • Hoskin T.L.
      • Sampaio S.M.
      • et al.
      Carotid endarterectomy in SAPPHIRE-eligible high-risk patients: implications for selecting patients for carotid angioplasty and stenting.
      • Gasparis A.P.
      • Ricotta L.
      • Cuadra S.A.
      • Char D.J.
      • Purtill W.A.
      • van Bemmelen P.S.
      • et al.
      High-risk carotid endarterectomy (CEA): facts or fiction.
      • Simonian G.T.
      • Pappas P.J.
      • Padberg Jr, F.T.
      • Samit A.
      • Silva Jr, M.B.
      • Jamil Z.
      • et al.
      Mandibular subluxation for distal internal carotid exposure: technical considerations.
      • AbuRahma A.F.
      • Abu-Halimah S.
      • Bensenhaver J.
      • Nanjundappa A.
      • Stone P.A.
      • Dean L.S.
      • et al.
      Primary carotid artery stenting versus carotid artery stenting for postcarotid endarterectomy stenosis.
      While CEA can be successfully performed in these situations, particularly when the tissues of the ipsilateral neck are not scarred and fibrotic, these situations can increase the risk of wound infection, difficulty of dissection, and potentially, the incidence of cranial nerve injury. The presence of a short, thick neck in an obese patient may make dissection more tedious but has not in itself proven to be associated with increased operative risk.
      Anatomic factors to consider with CAS are related to access issues. Successful CAS requires remote access of the ICA artery using a stable platform to avoid the intravascular motion of sheaths, stents, and protection devices during the procedure. Anatomic factors that may complicate this process include aortoiliac tortuosity, a sharply angulated aortic arch (type III), or a carotid lesion with more than two 90° bends within a short distance of the target lesion.
      • Setacci C.
      • Chisci E.
      • Setacci F.
      • Iacoponi F.
      • de Donato G.
      • Rossi A.
      Siena carotid artery stenting score: a risk modeling study for individual patients.
      Significant distal ICA tortuosity may also complicate the placement and stabilization of a distal embolic protection device. An aortic arch with heavy calcium or a high atherosclerotic burden is also associated with an increased risk with CAS. This is felt to be the main reason that CAS results are worse in patients aged >80 years.
      • White R.A.
      • Sicard G.A.
      • Zwolak R.M.
      • Sidawy A.N.
      • Schermerhorn M.L.
      • Shackelton R.J.
      • et al.
      Society of Vascular Surgery vascular registry comparison of carotid artery stenting outcomes for atherosclerotic vs nonatherosclerotic carotid artery disease.
      • Lam R.C.
      • Lin S.C.
      • DeRubertis B.
      • Hynecek R.
      • Kent K.C.
      • Faries P.L.
      The impact of increasing age on anatomic factors affecting carotid angioplasty and stenting.

      Patient characteristics

      It seems intuitive that the risk of periprocedural events after CEA or CAS might be increased in patients presenting with severe comorbid conditions, including dialysis-dependent renal failure, New York Heart Association class III or IV heart disease, left ventricular ejection fraction <30%, class III or IV angina pectoris, left main or multivessel coronary disease, severe aortic valvular disease, oxygen- or steroid-dependent pulmonary disease, or both, contralateral carotid occlusion, and advanced age. However, little data exist to support one therapy over another in these patients.
      • Mas J.L.
      • Chatellier G.
      • Beyssen B.
      • Branchereau A.
      • Moulin T.
      • Becquemin J.P.
      • et al.
      Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis.
      • Massop D.
      • Dave R.
      • Metzger C.
      • Bachinsky W.
      • Solis M.
      • Shah R.
      • et al.
      Stenting and angioplasty with protection in patients at high-risk for endarterectomy: SAPPHIRE Worldwide Registry first 2,001 patients.
      In fact, defining a high-risk patient is much more subjective than defining a high-risk lesion.
      • Mozes G.
      • Sullivan T.M.
      • Torres-Russotto D.R.
      • Bower T.C.
      • Hoskin T.L.
      • Sampaio S.M.
      • et al.
      Carotid endarterectomy in SAPPHIRE-eligible high-risk patients: implications for selecting patients for carotid angioplasty and stenting.
      • Gasparis A.P.
      • Ricotta L.
      • Cuadra S.A.
      • Char D.J.
      • Purtill W.A.
      • van Bemmelen P.S.
      • et al.
      High-risk carotid endarterectomy (CEA): facts or fiction.
      • Kang J.L.
      • Chung T.K.
      • Lancaster R.T.
      • Lamuraglia G.M.
      • Conrad M.F.
      • Cambria R.P.
      Outcomes after carotid endarterectomy: is there a high-risk population? A National Surgical Quality Improvement Program report.
      • Bangalore S.
      • Kumar S.
      • Wetterslev J.
      • Bavry A.A.
      • Gluud C.
      • Cutlip D.E.
      • et al.
      Carotid artery stenting vs carotid endarterectomy: meta-analysis and diversity-adjusted trial sequential analysis of randomized trials.
      As will be seen later, CAS is associated with a lower incidence of cardiac events than is seen in CEA. Therefore, CAS would be preferred over CEA when severe cardiac comorbidities exist in neurologically symptomatic patients. Chronic renal insufficiency has been associated with increased risk of stroke and death after CAS
      • Saw J.
      • Gurm H.S.
      • Fathi R.B.
      • Bhatt D.L.
      • Abou-Chebl A.
      • Bajzer C.
      • et al.
      Effect of chronic kidney disease on outcomes after carotid artery stenting.
      • Jackson B.M.
      • English S.J.
      • Fairman R.M.
      • Karmacharya J.
      • Carpenter J.P.
      • Woo E.Y.
      Carotid artery stenting: identification of risk factors for poor outcomes.
      and CEA.
      • Hamdan A.D.
      • Pomposelli F.B.
      • Gibbons G.W.
      • Campbell D.R.
      • LoGerfo F.W.
      Renal insufficiency and altered postoperative risk in carotid endarterectomy.
      • Ascher E.
      • Marks N.A.
      • Schutzer R.W.
      • HIngorani A.P.
      Carotid endarterectomy in patients with chronic renal insufficiency: a recent series of 184 cases.
      Univariate and multivariate analysis both show that the risk of death, stroke, and MI after CAS at 6 months was associated with hazard ratios >2.5 among patients with chronic kidney disease.
      • Jackson B.M.
      • English S.J.
      • Fairman R.M.
      • Karmacharya J.
      • Carpenter J.P.
      • Woo E.Y.
      Carotid artery stenting: identification of risk factors for poor outcomes.
      Chronic renal insufficiency also increases the risk of stroke after CEA (1.08% to 5.56%). Among asymptomatic patients with cardiac or renal insufficiency, best medical therapy may be preferable to CAS or CEA. CEA or CAS may be considered among symptomatic high-risk patients with moderate to severe carotid stenosis, but the effectiveness over medical therapy is not well established.
      There are conflicting data on the influence of contralateral occlusion on the outcome of CEA or CAS. NASCET reported that a contralateral occlusion increased the risk of stroke after CEA from 5.8% to approximately 14%.
      North American Symptomatic Carotid Endarterectomy Trial
      Methods, patient characteristics, and progress.
      However, most reports regarding contralateral occlusion do not bear this observation out, and a meta-analysis of the literature suggests a much more modest increase, from 2.4% to 3.7%.
      • Maatz W.
      • Köhler J.
      • Botsios S.
      • John V.
      • Walterbusch G.
      Risk of stroke for carotid endarterectomy patients with contralateral carotid occlusion.
      • Rockman C.B.
      • Su W.
      • Lamparello P.J.
      • Adelman M.A.
      • Jacobowitz G.R.
      • Gagne P.J.
      • et al.
      A reassessment of carotid endarterectomy in the face of contralateral carotid occlusion: surgical results in symptomatic and asymptomatic patients.
      This was statistically significant, but the results remain within the AHA recommended guidelines. Several single-center studies have shown excellent results in patients with contralateral carotid occlusion.
      • Mackey W.C.
      • O'Donnell Jr, T.F.
      • Callow A.D.
      Carotid Endarterectomy contralateral to an occluded carotid artery: perioperative risk and late results.
      • Halliday A.
      • Harrison M.
      • Hayter E.
      • Kong X.
      • Mansfield A.
      • Marro J.
      • et al.
      10-year stroke prevention after successful carotid endarterectomy for asymptomatic carotid stenosis (ACST-1): a multicentre randomised trial.
      A possible explanation for this discrepancy is an inadequate sample size in the single-center studies. Alternatively, a more consistent technique of intraoperative management in single-center reports, including, algorithms for maintaining intraoperative cerebral perfusion, are more likely to occur in single-center experience than in multicentered studies.
      CEA is associated with a lower stroke risk than CAS in patients aged >80 years.