Indications for Carotid Endarterectomy in Patients With Asymptomatic and Symptomatic Carotid Stenosis

Introduction

Management of extracranial internal carotid artery stenosis has been one of the most robustly studied topics in cerebrovascular neurology and neurosurgery in the past several decades. Despite multiple high-quality multicentered studies, there remains a certain degree of uncertainty when determining appropriate treatment of this rather common disease. Population studies have suggested that extracranial carotid stenosis alone is responsible for at least 8.0% of ischemic strokes. Furthermore, approximately 5%–10% of adults ages 65 years or older have been found to have 50% or more carotid stenosis. When taking into account the incidence of approximately 2160 strokes per day in the United States alone, the relevance of understanding and appropriately managing carotid disease becomes quickly apparent.

This chapter will discuss the diagnosis and treatment options available for extracranial carotid artery stenosis. In doing so, we will review the pertinent literature that informs current clinical decision making regarding best management of carotid disease.

Diagnosis

Given that carotid stenosis significantly contributes to risk of stroke, identification and diagnosis of stenosis are important, especially because patients are often asymptomatic. Indeed, asymptomatic carotid stenosis portends an annual risk of neurologic event (transient ischemic attack [TIA], amaurosis fugax, or stroke) of 2%–5% for 50%–80% stenosis and 1.7%–18% for greater than 80% stenosis. Identification of asymptomatic carotid stenosis often occurs during routine medical screening and is found by identification of carotid bruit, which leads to referral for more advanced workup. However, as a screening tool, auscultation of carotid bruit is rather nonspecific and insensitive. Only approximately one-third of patients with bruits have been found to have hemodynamically significant stenosis, and, conversely, only half of patients with significant stenosis are found to have bruits. As such, more advanced techniques are required for diagnosis of stenosis, which has raised the question of value of universal carotid stenosis screening. Although carotid disease is a significant contributor to stroke, the relatively low prevalence and the high risks of treatment (which will be discussed) has lead the US Preventative Service Task Force to recommend against carotid screening in the general population. ^, Thus workup should, perhaps, be reserved for patients who are deemed to be at particularly high risk, such as smokers, vasculopaths, and any symptomatic individuals.

Because severity of stenosis is directly correlated to risk of neurologic event, assessment of degree of stenosis is of utmost importance. In addition, certain plaque characteristics such as degree of plaque ulceration and intraplaque hemorrhage can be associated with increased risk. ^, For this reason, any diagnostic technique used must be able to provide adequate resolution to properly risk stratify patients based on these characteristics. The main studies for workup of carotid stenosis include carotid duplex Doppler ultrasound, computed tomography angiography (CTA), magnetic resonance angiography (MRA), and conventional digital subtraction cerebral angiography (DSA), each of which has its own benefits and drawbacks ( Fig. 76.1 ).

Given its low cost and noninvasive character, carotid ultrasound is often the initial study of choice for evaluation of carotid disease. Carotid stenosis is assessed with gray-scale, color, and spectral Doppler ultrasound for the presence of plaque, peak systolic velocity, internal carotid artery (ICA) to common carotid peak systolic velocity ratio, and ICA end-diastolic velocity (see Fig. 76.1A ). Stenosis is graded as less than 50%, 50%–69%, 70% or greater, near occlusion, and total occlusion. ^, Additional techniques to assess plaques for characteristics beyond degree of stenosis such as ulceration surface area and plaque rupture have been suggested, including microbubble contrast-enhanced ultrasound; however, such studies are not yet commonplace. A major drawback to carotid ultrasound is the degree of intratechnician variability and the risk of improper insonation, which highlights the importance of institutional quality assessment and standardization. ^,

Magnetic resonance imaging (MRI) and MRA can provide detailed assessment of stenosis as well as the added benefit of high soft tissue resolution, allowing for the assessment of plaque vulnerability characteristics (see Fig. 76.1B ). ^, However, low signal-to-noise ratios on lower tesla magnets, high costs, and inaccessibility in certain centers render widespread application of MRI difficult. ^,

CTA has been used routinely for characterization of stenosis (see Fig. 76.1C ). CTA can demonstrate detailed images of the carotid over its entire course and provide anatomic information regarding the location of the carotid bifurcation to other structures for surgical planning. However, CTA requires contrast and ionizing radiation. Furthermore, calcification artifact on computed tomography (CT) can lead to inaccuracies in stenosis assessment.

Digital subtraction cerebral angiography has been called the “gold standard” for assessment of carotid stenosis, but given the invasiveness of testing, the risk of contrast and radiation exposure, the risk of stroke, and the presence of the aforementioned alternatives, its routine usage for carotid disease has certainly curtailed (see Fig. 76.1D ).

In light of the fact that there is some controversy regarding the best modality for diagnosis and plaque characterization, more than one noninvasive modality can be used for confirmatory testing, as is our common practice.

Treatment Options

Once carotid stenosis is diagnosed in either symptomatic or asymptomatic patients, the various treatment options must be considered. The options include medical management alone, carotid endarterectomy (CEA), and carotid artery stenting (CAS). Fortunately, there is a large body of literature with multiple prospective randomized trials that exists to help inform clinical decision making.

Medical Treatment

Discussion of medical therapy in cases of both symptomatic and asymptomatic carotid stenosis is crucial whether or not a patient’s conditions warrants surgical intervention. Use of currently available medical therapies, including newer antiplatelet agents, ß blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins, improve overall cardiovascular disease in these patients. This general cardiovascular disease modification is of concern because carotid stenosis patients have high incidence of other cardiovascular events. In a study of asymptomatic carotid stenosis, yearly cardiac event and cardiac death rates in patients with severe stenosis were found to be 8.3% and 6.5%, respectively. To this end, in addition to blood pressure reduction, smoking cessation and glucose control should be pursued, which can provide both systemic benefits as well as specific benefits in stroke reduction.

Aspirin has been widely used as a therapy in patients with carotid artery stenosis and has become a backbone of the medical armamentarium against this disease. Part of the evidence in support of aspirin stems from improved outcomes in patients who ultimately underwent CEA while on low-dose aspirin versus patients who did not receive aspirin. Randomized control trials of CEA with and without aspirin from the 1990s demonstrated a reduction in stroke in the short-term period following CEA. In addition, it was found that low-dose aspirin was superior to high-dose aspirin at preventing periprocedural cardiovascular events (stroke, myocardial infarction [MI], and death) for up to 3 months. Based on the existing body of literature, in 2016, the US Preventative Service Task Force updated its recommendation regarding aspirin use for prevention of cardiovascular events in all patients. It was ultimately determined that low-dose aspirin (≤100 mg) did provide a 14% reduction in nonfatal stroke. This reduction was not noted when all doses of aspirin were included, although a reduction in nonfatal MI was seen in both instances. No significant difference was found in reduction in rates of cardiovascular death. As such, use of low-dose aspirin remains a staple in the treatment of patients with CAS whether or not patients will ultimately undergo surgery.

In the era of novel antiplatelet and anticoagulants, the question of dual antiplatelet and antithrombotic therapy has arisen. Multiple combinations of aspirin and other drugs have been investigated with mixed results. A reduction in transcranial Doppler evidence of microemboli was found for patients with symptomatic intracranial or extracranial stenosis when taking combination aspirin and clopidogrel versus aspirin alone. Both the ESPS-2 and ESPRIT studies found a significant benefit of combination aspirin and dipyridamole compared with aspirin or dipyridamole alone when used for secondary stroke prevention in previous stroke patients. ^, The CHARISMA trial echoes these findings for symptomatic patients. This trial assessed the use of clopidogrel and aspirin versus aspirin alone in 15,603 patients at risk for all types of atherothrombotic events. It found that for symptomatic patients there was a relative benefit of combination therapy, which did not extend to asymptomatic “high-risk” patients. A study of current practice patterns in the United States somewhat reflects these findings: one of six patients undergoing CEA were on clopidogrel prior to CEA and were more likely to have symptomatic stenosis preoperatively.

In addition to use of antiplatelet agents, statins have become a mainstay in the treatment of carotid artery stenosis. Subgroup analysis of the SPARCL trial found that symptomatic carotid stenosis patients on atorvastatin benefited from a 33% stroke risk reduction versus those on placebo. The upshot of these data is rather profound because many of the landmark clinical trials comparing medical intervention to CEA did not uniformly employ the use of statins. Based on the current body of evidence, it is difficult to rigorously compare optimal medical therapy to CEA for carotid stenosis. Results of the ongoing CREST-2 trial, which aims to better assess this crucial question, are still pending, but until these results are available, decision making is largely guided by the large randomized trial results available. ^,

Carotid Revascularization

Over the years, many high-quality randomized-control trials have assessed the risk and benefits of CEA. These studies have persisted as the backbone for surgical decision making in this disease. In general, these studies are segregated based on presence or absence of symptoms and will be reviewed in this manner.