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. 2009 Apr;84(4):362–368. doi: 10.1016/S0025-6196(11)60546-6

Treatment of Carotid Artery Stenosis: Medical Therapy, Surgery, or Stenting?

Giuseppe Lanzino 1,✉, Alejandro A Rabinstein 1, Robert D Brown Jr 1
PMCID: PMC2665982  PMID: 19339655

Abstract

With the aging of the general population and the availability of noninvasive imaging studies, carotid artery stenosis is a disease commonly seen in general medical practice. Differentiation between symptomatic and asymptomatic disease is critical to the treatment course because the natural history differs markedly between them. Antiplatelet therapy and aggressive treatment of vascular risk factors are the mainstays of medical therapy. Class I evidence shows that carotid endarterectomy (CEA) is effective in preventing ipsilateral ischemic events in patients with symptomatic moderate- and high-grade stenosis. The procedure is also effective in selected patients with asymptomatic stenosis, but the benefit is marginal. In the past decade, carotid angioplasty and stenting has been proposed as a valid alternative to CEA. Currently, it is unclear whether carotid angioplasty and stenting is as safe as CEA in patients with carotid artery stenosis who need invasive treatment. Large clinical trials are under way to answer this question.

CAS = carotid angioplasty and stenting; CEA = carotid endarterectomy; RCT = randomized controlled trial; TIA = transient ischemic attack

Carotid artery stenosis is a common diagnosis in general medical practice. Several randomized controlled trials (RCTs) have shown that carotid endarterectomy (CEA) is effective in preventing ipsilateral ischemic events in selected patients with the disease.1 These studies were mostly done between the late 1980s and mid-1990s. Since then, medical therapy has evolved, with newer antiplatelet agents and more aggressive and effective management of risk factors associated with carotid artery stenosis. Recently, carotid angioplasty and stenting (CAS) was proposed as a valid alternative to CEA. This review summarizes recent data on the management of carotid artery stenosis.

SYMPTOMATIC VS ASYMPTOMATIC CAROTID ARTERY STENOSIS

A clear separation between symptomatic and asymptomatic carotid artery stenosis is critical. Extrapolations on the natural history with medical treatment only or on the benefit from invasive procedures are based on precise definitions of symptomatic and asymptomatic disease. A patient with carotid artery stenosis is considered symptomatic if the patient has transient or permanent focal neurologic symptoms related to the ipsilateral retina or the cerebral hemisphere. Symptoms of carotid artery stenosis include ipsilateral transient visual obscuration (amaurosis fugax) from retinal ischemia; contralateral weakness or numbness of an arm, a leg, or the face, or of a combination of these sites; visual field defect; dysarthria; and, in the case of dominant (usually left) hemisphere involvement, aphasia.

In daily clinical practice, carotid artery stenosis is found in many patients during evaluation of ill-defined episodes of “dizziness,” generalized subjective weakness, syncope or near-syncope episodes, “blurry vision,” or transient positive visual phenomena (such as “floaters” or “stars”). These nonspecific symptoms in patients with carotid artery stenosis do not qualify as symptomatic ischemic events; these patients are considered asymptomatic even in the presence of high-grade carotid artery stenosis.

DIAGNOSIS

Carotid Bruits

Carotid auscultation should be part of the routine physical examination of patients with risk factors for vascular disease. Although carotid bruits have limited value for the diagnosis of carotid artery stenosis, they are good markers of generalized atherosclerosis. The presence of a carotid bruit is associated with increased risk of vascular disease, including stroke, myocardial infarction, and cardiovascular death.2

For asymptomatic patients with vascular risk factors, carotid auscultation is a sufficient screening test. However, for patients with symptoms of transient ischemic attack (TIA) or stroke, the evaluation for carotid artery disease cannot be limited to auscultation of the neck because carotid bruits have relatively low sensitivity for the detection of moderate or severe carotid artery stenosis.3 Specificity is good for carotid artery disease in general, but it is actually lower for greater degrees of stenosis.3 Because bruits are generated by turbulent flow, they may be strong with mild stenosis and may even disappear when the stenosis becomes critical and causes marked restriction of flow. Therefore, symptomatic patients must be evaluated with imaging studies.

Imaging Studies

The definition of hemodynamically significant carotid artery stenosis is based on data from the RCTs on CEA. Exact quantification of the degree of stenosis is crucial in selecting proper treatment. This quantification is particularly important for patients with asymptomatic carotid artery stenosis because of the marginal benefit they receive from surgery.

Doppler ultrasonography, which is readily available and noninvasive, is usually the first diagnostic imaging tool used to screen for carotid artery stenosis. However, it is highly dependent on operator experience and skill. When compared with catheter angiography, Doppler ultrasonography has a sensitivity of 86% and a specificity of 87% for the detection of hemodynamically significant carotid artery stenosis.4

Catheter angiography is the criterion standard for defining the degree of stenosis and the morphologic features of the offending plaque. However, catheter angiography is neither feasible nor recommended in every patient because of its risks and costs. Computed tomographic angiography and magnetic resonance angiography have gained increasing popularity for use in the diagnosis of carotid artery stenosis, often replacing conventional catheter angiography. In our practice, magnetic resonance angiography or computed tomographic angiography is used as a confirmatory test after results of a Doppler study are suggestive of hemodynamically significant stenosis in an asymptomatic patient. Among symptomatic patients, a Doppler study is done as part of the emergency evaluation of every patient with TIA or stroke.5 If a patient is considered for invasive treatment, these angiographic techniques are subsequently performed for improved definition of the stenosis. Invasive treatment is considered for symptomatic patients with stenosis greater than 50%6 and for asymptomatic patients with stenosis greater than 60%.7,8

Carotid artery occlusion may be suspected because of ultrasonographic results, but it should be confirmed with noninvasive or invasive angiography, especially in symptomatic patients. For an occluded carotid artery, invasive treatment has no role except in the cases of a few carefully selected patients.

TREATMENT

Symptomatic Carotid Artery Stenosis

Prompt evaluation and triage of patients with symptomatic carotid artery stenosis are essential to minimize the risk of early recurrent cerebrovascular events. Prospective studies have shown that the risk of ipsilateral stroke is high within the first 90 days, and especially within the first month, after a TIA.9 Urgent initiation of treatment can reduce this risk by up to 80%.9

Recently, a scoring system was proposed, prospectively validated, and widely adopted to estimate the short-term risk of ipsilateral stroke after a TIA10 (Table). The system is named with the acronym ABCD2, derived from the 5 main components used to compound the score: age, blood pressure, clinical features, duration of symptoms, and diabetes mellitus. A patient with a TIA and an ABCD2 score of 0 to 3 has a 1.2% risk of stroke within 7 days, as opposed to a 5.9% risk with a score of 4 or 5 and an 11.7% risk with a score of 5 or 6.10 High ABCD2 scores appear to identify patients with moderate or severe carotid artery stenosis.9 In our emergency department, we also perform screening with carotid duplex ultrasonography for all patients with suspected anterior circulation TIA. This practice has been useful for patient triage and has been associated with a low rate of strokes in the first week after the TIA.5

TABLE.

Criteria and Points of the ABCD2 Scoring Systema

graphic file with name 362tbl.jpg

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Patients with symptomatic severe carotid artery stenosis should undergo invasive treatment unless the risk of the intervention is considered to be prohibitively high (eg, extremely severe cardiopulmonary disease, recent cerebral infarction of large size or with hemorrhagic conversion). In addition, aggressive treatment of vascular risk factors and antiplatelet therapy must be initiated promptly because they are crucial to the prevention of recurrent strokes after carotid revascularization.

Gradual blood pressure reduction (ie, over the period of a few days) is safe in most patients,11 but sudden decreases in blood pressure should be avoided, and antihypertensive therapy should be administered cautiously for patients with severe bilateral stenosis or critical unilateral stenosis. The use of a statin medication should be considered even for patients with mild or moderate hypercholesterolemia,12 with the goal of decreasing the low-density lipoprotein cholesterol value to less than 70 mg/dL (to convert to mmol/L, multiply by 0.0259).13 Antiplatelet therapy should be started immediately; aspirin is the agent most commonly used. Some evidence shows that the combination of aspirin and clopidogrel may be more effective than aspirin alone when prescribed within 24 hours of a TIA or a minor stroke14; however, combination therapy is not generally recommended.15,16 The addition of clopidogrel therapy increases the risk of hemorrhagic complications and might impair hemostasis in patients undergoing CEA. Therefore, the safety of adding clopidogrel to aspirin for patients with symptomatic carotid artery stenosis needs to be confirmed before this combination can be recommended for routine use. The combination of aspirin and extended-release dipyridamole has not been specifically evaluated in patients with acute symptomatic carotid disease. Symptomatic carotid artery stenosis is not an indication for oral anticoagulation. It is also prudent to consider screening these patients with a stress test because of the possibility of concomitant coronary artery disease, even in the absence of angina or other symptoms of myocardial ischemia.17

In patients with symptomatic carotid artery disease, CEA is effective in preventing future ipsilateral ischemic events, provided that the perioperative combined risk of stroke and death is not higher than 6%.13 Its effect is marked in patients with high-grade (>70%) stenosis, with 8 patients needed to be treated to prevent 1 ipsilateral stroke in a 2-year period.6 The benefit is still present, although less pronounced, in symptomatic patients with a moderate (50%-75%) degree of stenosis, with 20 patients needed to be treated to prevent 1 ipsilateral stroke during a 2-year period.6

The observation that the risk of ipsilateral stroke is much higher in the first few weeks after a qualifying TIA than it is later has important therapeutic implications. To maximize the benefit of surgery, treatment should be performed on an urgent basis after a TIA. Pooled analysis of the RCTs suggested that the benefit from CEA was maximal in patients who had the operation within 2 weeks of a qualifying event. In patients with symptomatic stenosis of 70% to 99%, the absolute risk reduction decreased from 23% to 16% and then to 8% when patients were treated within 2 weeks, between 2 and 4 weeks, and after 4 weeks, respectively.18 The decreasing benefit of CEA with increasing time from the qualifying ischemic event was particularly evident in women.19 In fact, the benefit of treatment was lost in women when treatment was delayed more than 2 weeks.19

Traditionally, surgeons have been reluctant to operate within 1 month of a qualifying TIA or a minor stroke because of a perceived higher risk of periprocedural complications with this timeline than with a later one.18 However, subgroup analysis of the RCTs showed that the perioperative risks of stroke and death were not increased in patients who underwent an operation within 2 weeks of the qualifying event.19 Recent guidelines for secondary stroke prevention recommend that CEA be performed within 2 weeks for patients presenting with a TIA or minor stroke.13

Asymptomatic Carotid Artery Stenosis

With the wide availability of various noninvasive diagnostic modalities, most patients who receive a diagnosis of carotid disease are asymptomatic. For many of these patients, intensive medical treatment may be the most appropriate therapeutic option.

Hypertension should be treated to maintain blood pressures consistently below 140/90 mm Hg20 except for patients with diabetes mellitus or kidney disease, in whom blood pressures should stay below 130/80 mm Hg. Currently, it is unclear whether certain antihypertensive agents may be more effective than others in reducing the progression of carotid atherosclerosis21; therefore, the presence of comorbid conditions and the cost should guide agent selection.

Lipid-lowering therapy should preferentially include a statin and should aim to achieve a low-density lipoprotein cholesterol value of less than 100 mg/dL. For patients with numerous vascular risk factors or coexistent symptomatic coronary artery disease, a target value of less than 70 mg/dL may be preferable. Smoking cessation is imperative, and any necessary counseling and medical therapies for smoking cessation should be used. Diabetes screening is necessary for all patients with carotid atherosclerosis, and patients with diabetes should be treated.

Patients with asymptomatic carotid artery stenosis should be treated with aspirin. No proof exists of added benefit due to combining aspirin with extended-release dipyridamole or with clopidogrel for asymptomatic carotid artery stenosis. Patients with aspirin allergy should be treated with clopidogrel alone. Aspirin plus clopidogrel is appropriate for patients with concomitant symptomatic coronary artery disease, recent coronary stenting, and severe peripheral arterial disease.

A regular program of aerobic exercise (>30 minutes on 5 or more days per week) should be initiated, along with a diet low in saturated fat, to maintain a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of less than 25 kg/m2.13 In addition, all patients with documented carotid artery disease should be instructed about stroke symptoms (especially but not exclusively symptoms expected in accordance with the side affected by the stenosis) and about the importance of seeking immediate medical attention if symptoms occur.

The decision on whether to implement invasive treatment in patients with asymptomatic carotid artery stenosis is a difficult one. The benefit of CEA in RCTs was marginal. The 2 largest RCTs comparing CEA with medical treatment for asymptomatic patients showed that surgery provided only a modest benefit in stroke prevention.7,8 In these studies, CEA reduced the risk of stroke from 2% per year to 1% per year.

In the analysis of these 2 trials and their conclusions, an important consideration is that the enrolled patients constituted a highly selected group; they are not necessarily representative of patients routinely seen in clinical practice. For example, about 42,000 people were screened in the Asymptomatic Carotid Atherosclerosis Study, but only 1662 people with an angiographically confirmed stenosis of 60% or greater were randomly assigned to treatment.8 The medical treatment arm in these RCTs was not uniformly defined and it did not include interventions currently considered optimal medical management, such as intensive decreases in blood pressure and lipid concentrations. It is unknown whether current standard medical therapy can decrease the relative benefit from CEA in patients with asymptomatic carotid artery stenosis by decreasing the rate of stroke.

Patients with a life expectancy of less than 5 years are unlikely to benefit from the modest risk reduction afforded by surgery.7 In the Asymptomatic Carotid Surgery Trial, surgery did not benefit patients aged 75 years or older because of the excess mortality rate at follow-up in these patients—a rate related to such noncerebrovascular events as myocardial infarction and cancer.7 With the advent of CAS, which is perceived to be a less invasive treatment, this consideration is particularly important because more patients with severe systemic comorbidities are being considered for carotid revascularization. Surgical team selection is also important to maximize the modest benefit afforded by CEA in asymptomatic disease. In asymptomatic patients with severe carotid artery stenosis, the benefit is only maintained when the perioperative risks of stroke and death are below 3%.8,13

Identification of asymptomatic patients who are at increased risk of stroke would improve the yield of prophylactic invasive treatment. Predictors of increased risk of ipsilateral ischemic events in asymptomatic patients with carotid artery stenosis are the following: a stenosis of increased severity,22 a progressive stenosis, a history of contralateral symptomatic carotid artery stenosis,7 and increased serum creatinine concentrations.22 Early reports suggest that detailed imaging may allow identification of carotid plaques that are more likely to cause symptoms. However, these studies are preliminary and require confirmation.

CEA OR STENTING?

The criterion standard for invasive treatment of carotid artery stenosis is CEA. Recently, CAS has been proposed as a valid alternative to CEA. Compared with CEA, CAS (Figure) has the advantage that it can be done with the patient under mild sedation, requires no incision, carries no risk of cranial nerve palsy, and has fewer cardiovascular complications. Over the years, CEA has been shown to be safe (when done by operators with acceptably low morbidity and mortality outcomes), effective in preventing ipsilateral strokes, and durable (ie, a low incidence of restenosis). For its acceptance as a valid alternative to CEA, CAS must fulfill the same criteria of safety, effectiveness, and durability.

FIGURE.

FIGURE.

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Carotid angioplasty and stenting. A, Large catheter (guide catheter, not shown) is placed in the common carotid artery proximal to the stenosis. Through this catheter, a filter wire is used to cross the stenosis and deploy a filter (distal protection) in the internal carotid artery distal to the plaque. The filter captures emboli dislodged during the procedure. B, Angioplasty (predilatation) of the plaque is performed with an angioplasty balloon, followed by stent deployment (C). Occasionally, angioplasty may be necessary after stenting to further dilate residual stenosis. D, The filter is “captured” and withdrawn into the guide catheter. The procedure is done with full heparinization. Patients receive maintenance dual antiplatelet therapy, usually aspirin plus clopidogrel, for at least 4 to 6 weeks.

The safety of CAS compared with that of CEA has been studied in RCTs1,23 and in prospective (often industry-sponsored) registries.24 These recent studies have several common features, including prospective data collection, outcome assessment by independent neurologists, and similar end points of myocardial infarction, stroke, and death within 30 days of the procedure. Although the results of these studies are far from resolving the debate on the safety of CAS vs CEA, they have identified high-risk subgroups. It was thought that the CAS procedure, being less invasive than CEA, could be advantageous for older patients. However, paradoxically, subgroup analyses of prospective studies have consistently shown that greater age is associated with a higher risk of periprocedural morbidity and death after CAS but not necessarily after CEA.25-27 After CAS, symptoms that are recent (within 2 weeks of the procedure) are also associated with increased complication rates.25 Final analysis of larger multicenter, non-industry-sponsored trials comparing CAS with CEA will be available soon. It is hoped that the results of these studies will answer most of the remaining questions regarding the safety and relative value of CAS.

A meta-analysis of published RCTs indicated that the risk of stroke within 30 days of the intervention was slightly higher in the CAS than the CEA group.23 However, the long-term (2-3 years) effectiveness of CAS in preventing ipsilateral ischemic events is supported by randomized studies showing that the long-term incidence of ipsilateral strokes is not different between CAS and CEA.28-30 Data on the incidence of restenosis are preliminary, but restenosis rates reported after CAS are relatively low.28,29 More importantly, most restenoses are asymptomatic and therefore of unclear clinical importance. Moreover, it is likely that restenosis rates may decrease as the stent technology continues to improve.

While clinicians await the conclusion of the large RCTs, CAS should be considered for patients with indication for carotid revascularization and high surgical risk. At this time, the Centers for Medicare and Medicaid Services only reimburses the cost of CAS for patients with symptomatic carotid artery stenosis of a severity of at least 70% who are considered high-risk patients for surgery. In all other patient categories, the procedure is reimbursed only in the setting of one of the numerous ongoing postmarketing registries or clinical trials.

CONCLUSION

Carotid artery stenosis is a problem commonly seen in clinical practice. Differentiation between symptomatic and asymptomatic patients with carotid artery stenosis is essential to tailor therapy properly. Antiplatelet drug therapy and aggressive correction of risk factors are the mainstays of medical therapy. Expedited evaluation and triage of symptomatic patients are of utmost importance to maximize the benefits of carotid artery revascularization. Carotid endarterectomy should be strongly considered for symptomatic patients with 70% to 99% stenosis and should also be considered for symptomatic patients with 50% to 69% stenosis if no other etiologic basis for the ischemic symptoms can be found. Surgery should be recommended only in selected patients with asymptomatic carotid artery stenosis because of the marginal benefit from revascularization in this patient population. The CAS procedure is a valid alternative to CEA for selected patients who have an indication for revascularization and are at high surgical risk. In the near future, analyses of the results of large ongoing and recently completed trials comparing CEA with CAS will likely help clarify the role of these procedures for different subgroups of patients with carotid artery disease.

Supplementary Material

CME Test
supp_84_4_362__index.html (626B, html)

On completion of this article, you should be able to (1) recognize symptoms of carotid artery stenosis, (2) apply evidence-based treatment to patients with asymptomatic and symptomatic artery carotid disease, and (3) formulate indications for invasive treatment of patients with asymptomatic and symptomatic carotid artery stenosis.

CME Questions About Carotid Artery Stenosis

  1. Which one of the following is not a symptom of carotid artery stenosis?

    1. Aphasia

    2. Contralateral weakness

    3. Bilateral “blurry vision”

    4. Dysarthria

    5. Visual field loss

  2. Which one of the following statements about carotid endarterectomy (CEA) best accords with the findings of the largest studies of CEA in patients with asymptomatic carotid artery stenosis?

    1. It is not effective

    2. It reduces the risk of ipsilateral stroke from 2% per year to 1% per year

    3. It is indicated in every patient older than 75 years who has asymptomatic carotid artery stenosis

    4. It is effective provided the perioperative risk of stroke or death is less than 7%

    5. It is indicated in patients with mild (<60%) carotid artery stenosis

  3. Which one of the following statements is true regarding carotid angioplasty and stenting (CAS) for carotid artery stenosis?

    1. It is safer than CEA

    2. It is a valid alternative to CEA in patients with high surgical risk

    3. It is associated with a risk of cranial neuropathies

    4. The restenosis rate after CAS is high (>50%)

    5. It should be recommended to every patient with carotid artery stenosis

  4. Which one of the following statements is not true regarding medical treatment of patients with symptomatic and asymptomatic carotid artery stenosis?

    1. The combination of aspirin and clopidogrel is indicated in every patient with carotid artery stenosis

    2. The use of a statin medication should be considered in patients with mild or moderate hypercholesterolemia

    3. Gradual blood pressure reduction is safe in most patients

    4. The combination of aspirin and clopidogrel increases the risk of bleeding complications

    5. Aggressive correction of risk factors for atherosclerosis is crucial, regardless of whether carotid revascularization is performed

  5. Which one of the following statements regarding randomized controlled trials of CEA for carotid artery stenosis is not true?

    1. In the Asymptomatic Carotid Atherosclerosis Study, 42,000 people with asymptomatic disease were screened but only 1662 people were randomly assigned to treatment

    2. In patients with symptomatic high-grade (>70%) stenosis, CEA is effective in preventing ipsilateral ischemic events

    3. Randomized trials of CEA vs CAS have definitively shown the superiority of CAS over CEA

    4. Although CEA is effective in preventing ipsilateral stroke in patients with moderate (50%-69%) carotid artery stenosis, this benefit is less than in patients with more severe (≥70%) disease

    5. Carotid endarterectomy is effective in selected patients with asymptomatic carotid artery stenosis greater than 60%

This activity was designated for 1 AMA PRA Category 1 Credit(s).™

Because the Concise Review for Clinicians contributions are now a CME activity, the answers to the questions will no longer be published in the print journal. For CME credit and the answers, see the link on our Web site at mayoclinicproceedings.com.

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