Approach

Carotid artery stenosis is the most common disorder affecting the extracranial carotid artery. Management of the stenosis is a cornerstone of stroke prevention. It is one of the most intensively studied vascular diseases and debated by multiple medical specialists since the introduction of carotid endarterectomy as a therapeutic option more than 70 years ago. Since then, carotid artery stenting was introduced as an endovascular alternative to carotid endarterectomy, and pharmacological therapy for stroke prevention has also evolved. Several randomised controlled trials performed within the past 3 decades form the basis for current treatment recommendations involving the three components of therapy (pharmacological, carotid endarterectomy, and carotid artery stenting).

Ongoing trials in the US (CREST-2) and Europe (ACTRIS) and the recently completed ECST-2 (European Carotid Surgery Trial 2) compare carotid intervention with intensive medical management, which may result in updates to treatment recommendations in the next few years. CREST-2: The carotid revascularization and medical management for asymptomatic carotid stenosis study: health and hope for patients at risk for stroke Opens in new window ​ClinicalTrials.gov: Endarterectomy combined with OMT vs OMT alone in patients with asymptomatic severe atherosclerotic carotid artery stenosis at higher-than-average risk of ipsilateral stroke Opens in new window European Carotid Surgery Trial 2 (ECST-2) Opens in new window

The current treatment approach is broadly based on the clinical presentation (asymptomatic versus symptomatic) and may be further modified based on uncommon presentations or aetiologies of stenosis.

The North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria are accepted worldwide for calculating the degree of stenosis and other criteria are rarely used. The NASCET criteria are used to define the degree of stenosis in this section.

Asymptomatic carotid artery stenosis

Although previous trials have consistently shown a moderate benefit from revascularisation surgery for asymptomatic stenosis, advances in medical therapy now question the absolute benefit from revascularisation for asymptomatic stenosis.

Pharmacotherapy is, therefore, the first-line therapy in asymptomatic patients. Aspirin is the preferred antiplatelet agent because of its known benefits in preventing myocardial infarction (MI) in vascular patients. In the presence of a contraindication to aspirin, clopidogrel is a reasonable alternative; other antiplatelet agents (e.g., dipyridamole) may be considered if neither aspirin or clopidogrel can be used, depending on availability.[2]​ Patients on anticoagulation (e.g., warfarin) for an unrelated indication should not be given antiplatelet agents for carotid stenosis except in special circumstances (e.g., presence of a stent), and should continue on the anticoagulant with the additional goal of preventing atheroembolic stroke.[1][33]

The selection of asymptomatic patients for carotid revascularisation should be guided by the severity of stenosis, and an assessment of the patient's comorbid conditions, life expectancy, surgeon-specific outcomes, and preferences of the patient concerning intervention.

The 2021 Society for Vascular Surgery guidelines and 2011 multi-society guidelines recommend carotid endarterectomy, in addition to the pharmacological treatment listed, for patients with asymptomatic carotid stenosis ≥70% if the risk of perioperative stroke, MI, and death is low.[1][14]​​​ The 2023 European Society for Vascular Surgery guidelines recommend that carotid endarterectomy should be considered in patients with asymptomatic stenosis ≥60% to 99% and an increased risk of late stroke, provided perioperative stroke/death rates are low (≤3%) and patient life expectancy exceeds 5 years, and if there are particular features suggesting an increased stroke risk.[2]​

Antiplatelet therapy should be started preoperatively to reduce the risk of complications such as stroke and MI. It should be initiated at diagnosis and continued indefinitely after the procedure.

Results from the CREST and ASCT-2 trials found that both stenting and endarterectomy had a similar low risk of complications and are similarly effective in reducing the risk of stroke.[34][35]​​​ It is therefore reasonable to perform carotid artery stenting as an alternative to endarterectomy when the patient is considered to be high risk for surgery​.[1][2][36]​​​ One meta-analysis of 7118 patients with asymptomatic carotid artery stenosis from seven randomised controlled trials compared carotid endarterectomy with carotid artery stenting. There was no significant difference between groups for the perioperative outcomes of stroke, death, or MI. However, carotid artery stenting was associated with a heightened risk of perioperative non-disabling stroke but not of perioperative disabling stroke or death, underscoring the nuanced considerations in treatment selection for this patient population.[37] ​This approach may differ in other countries. For example, in the UK, stenting in asymptomatic patients is only recommended within randomised controlled trials.[38] Dual antiplatelet therapy (e.g., aspirin plus clopidogrel) is preferred in patients with stents and is used for at least 4 weeks after stenting, followed by antiplatelet monotherapy indefinitely.​[2]

​As plaques within the carotid bulb enlarge and the overlying fibrin cap is eroded, ulcerations may appear over the surface. This becomes a source of atheroemboli to the retina and cerebral cortex. The majority of large ulcerations occur in association with high-grade stenoses and will warrant carotid endarterectomy on the basis of the degree of stenosis.

Asymptomatic patients with large ulcers in the presence of <50% stenosis form a therapeutic dilemma. These conditions are possible indications for carotid endarterectomy, but the recommendation is based on weak evidence, and such cases merit careful discussion in a multi-disciplinary team meeting.[2][39]

Risk factors such as cigarette smoking, hypercholesterolaemia, diabetes, and hypertension must be managed according to appropriate guidelines.[1][2] ​Lifestyle modifications include adopting a healthy diet and increased physical activity and exercise as appropriate.[1][2] Lipid-lowering therapy with statins (with or without ezetimibe) is recommended for patients with asymptomatic stenosis for prevention of cardiovascular events.[2] Patients undergoing endarterectomy or stenting should start or continue statin therapy prior to the procedure; statins should not be stopped during the perioperative period, and should be continued long term if tolerated.[2] Statins have a particularly important role in treating carotid stenosis caused by atherosclerosis and patients should be encouraged to persist with these medications. Addition of ezetimibe is recommended for those who do not reach lipid targets despite maximum tolerated dose of statin. Additional or alternative treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (monoclonal antibodies) should be considered for those patients who do not reach lipid targets despite maximum tolerated dose of statin and ezetimibe, or who are statin-intolerant.[2]

Symptomatic carotid artery stenosis

Symptomatic patients include those with transient ischaemic attack, stroke, and transient monocular blindness (amaurosis fugax).

These patients should undergo carotid endarterectomy if the ipsilateral carotid stenosis is ≥50%.[1][2][14]​​​​[40]​​​​ Rapid referral to a specialist as soon as the neurological event occurs is recommended, with early revascularisation (i.e., within 2 weeks) in patients whose neurological symptoms have stabilised.

Carotid stenting is more risky than carotid endarterectomy in older patients, but can be considered as an alternative to surgery in younger patients (aged 65 years or less) in centres where carotid stenting is regularly performed.[2][41][42]​​ It is reasonable to perform carotid artery stenting as an alternative to endarterectomy when the patient is considered to be high risk for surgery.[1]​​[2]

Antiplatelet therapy should be started preoperatively to reduce the risk of complications such as stroke and MI. It should be initiated at diagnosis (after imaging has excluded intracranial haemorrhage) and continued indefinitely after the procedure.[2] Aspirin alone, clopidogrel alone, or the combination of aspirin plus extended-release dipyridamole are preferred antiplatelet agents in symptomatic patients undergoing carotid endarterectomy.[1] Dual antiplatelet therapy (e.g., aspirin plus clopidogrel) is preferred in patients with stents and is used for at least 4 weeks after stenting, followed by antiplatelet monotherapy indefinitely.[2] For symptomatic patients not being considered for carotid endarterectomy or stenting, the 2023 European Society for Vascular Surgery guidelines recommend aspirin plus clopidogrel for 21 days followed by clopidogrel monotherapy, or long-term aspirin plus modified-release dipyridamole.[2] Other antiplatelet agents (e.g., ticagrelor or dipyridamole) may be considered if neither aspirin or clopidogrel can be used, depending on availability.[2]

All symptomatic patients should receive high-intensity statin therapy for prevention of cardiovascular events, treating to a target LDL-cholesterol level of <1.8 mmol/L (<70 mg/dL).[2] Addition of ezetimibe is recommended for those who do not reach lipid targets despite maximum tolerated dose of statin. Additional or alternative treatment with PCSK9 inhibitors should be considered for those patients who do not reach lipid targets despite maximum tolerated dose of statin and ezetimibe, or who are intolerant.[2] Patients should start or continue statin therapy prior to endarterectomy or stenting; statins should not be stopped during the perioperative period and should be continued long term if tolerated.[2]

Risk factors such as cigarette smoking, hypercholesterolaemia, diabetes, and hypertension must be managed according to appropriate guidelines.[1][2] Lifestyle modifications include adopting a healthy diet and increased physical activity and exercise as appropriate.[1][2]

Concurrent carotid and coronary artery stenosis

The combination of carotid endarterectomy and coronary bypass is associated with a perioperative stroke, MI, and death rate of 9% to 12%.[43] Therefore, the combined procedure is usually recommended for patients with symptomatic carotid stenosis and critically symptomatic coronary artery disease.[44]

Asymptomatic carotid stenosis may be addressed after coronary revascularisation in most patients, but a minority of patients with very tight bilateral carotid stenoses (70% to 99%) or those with a 70% to 99% stenosis and a contra-lateral occlusion may benefit from staged carotid endarterectomy and coronary bypass or synchronous carotid endarterectomy and coronary bypass.[2] Conversely, patients with symptomatic carotid stenosis and stable coronary disease may have carotid endarterectomy performed 1-4 weeks before coronary bypass.[1]

Routine screening for coronary artery disease is not recommended preoperatively in people without symptomatic coronary artery disease.[1][2] A history and physical examination plus ECG (as for any preoperative workup) are needed. Per American Heart Association recommendations, a history suggestive of coronary artery disease or an abnormal ECG should prompt further testing for coronary artery disease. This may involve a stress test or cardiac catheterisation.

Bilateral carotid artery stenosis

In asymptomatic people found to have bilateral carotid stenoses ≥70%, the higher-grade stenosis is generally addressed surgically first. In the case of equal degrees of stenosis, handedness is considered. For example, the left carotid may be surgically treated first in a right-handed person.

In symptomatic people found to have asymptomatic carotid stenosis in a contralateral carotid artery, the asymptomatic carotid stenosis is treated based on the merits of that stenosis. Generally if surgery is indicated, it might be undertaken electively several weeks after treatment related to the acute neurological episode. This is to allow resolution of and observation of neurological symptoms.

Relationship to any existing coronary artery disease may also need to be considered.

Antiplatelet therapy should be started preoperatively to reduce the risk of complications such as stroke and MI. It should be initiated at diagnosis and continued indefinitely after the procedure. If the patient undergoes endarterectomy, aspirin or clopidogrel monotherapy is recommended. Dual antiplatelet therapy (e.g., aspirin plus clopidogrel) is preferred in patients with stents and is used for at least 4 weeks after stenting, followed by antiplatelet monotherapy indefinitely.[2]

Risk factors such as cigarette smoking, hypercholesterolaemia, diabetes, and hypertension must be managed according to appropriate guidelines.[1][2]​ Lifestyle modifications include adopting a healthy diet and increased physical activity and exercise as appropriate.[1][2]

Carotid restenosis

Recurrent high-grade stenosis after a prior carotid endarterectomy or stenting occurs infrequently (approximately 6% over 2 years).[45] Restenosis is generally a consequence of neointimal hyperplasia when it occurs within the first 2 years after surgery; and commonly due to new atherosclerotic plaque when it occurs beyond 2 years after surgery. Residual stenosis is a stenosis found within 30 days of the carotid intervention.

There is ongoing controversy regarding the optimal treatment approach for this relatively rare occurrence.[2][45]​ In many countries, medical management is recommended in asymptomatic patients owing to the low risk of embolic stroke associated with neointimal hyperplasia. Revascularisation is reserved for symptomatic patients, and rarely for the infrequent cases of rapid progression. The method of revascularisation is not protocol driven and choice depends on the treating physician, but increasingly carotid stenting is considered first to avoid the morbidity associated with redo carotid endarterectomy.

In patients undergoing stenting for restenosis, dual antiplatelet therapy (e.g., aspirin plus clopidogrel ) is used for the first 1-3 months, followed by aspirin alone taken indefinitely.[28]

Risk factors such as cigarette smoking, hypercholesterolaemia, diabetes, and hypertension must be managed according to appropriate guidelines.[1][2]​​​ Lifestyle modifications include adopting a healthy diet and increased physical activity and exercise as appropriate.[1]​​[2]

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