Amar Krishnaswamy and Mehdi Shishehbor
Carotid atherosclerotic disease is an important cause of ischemic stroke and transient ischemic attack (TIA). Diagnosis is made using ultrasound, computed tomography, magnetic resonance angiography (MRA), or angiography. Treatment consists of medical therapy to address the risk factors responsible for the formation and progression of carotid atherosclerosis, and carotid endarterectomy (CEA) or carotid artery stenting (CAS) in appropriately selected patients.
EPIDEMIOLOGY
Approximately 800,000 people in the United States experience a stroke each year, with a 30-day mortality of 10%.1–3 Up to 500,000 more individuals suffer a TIA annually.1 The male-to-female ratio for strokes is greater at ages <65 years (1.50) and less at ages >75 years (0.76); overall, approximately 55,000 more women than men have a stroke each year. With respect to race, blacks have an almost twofold higher risk of first stroke than whites.
PATHOPHYSIOLOGY OF CAROTID ARTERY DISEASE
An estimated 87% of strokes are ischemic in nature, about 15% to 20% of which are attributed to complications of carotid atherosclerotic disease.1,4,5 Carotid stenosis can lead to ischemia via progressive narrowing and impairment of blood supply, or more commonly by providing a foundation for the formation of local plaque rupture and athero-thrombosis that embolizes distally. It is important to note that the severity of stenosis is predictive of ipsilateral stroke risk, with a 5-year risk of 7.8% in asymptomatic patients with <50% stenosis and 18.5% in patients with 75% to 94% stenosis.6 In patients with an occluded artery, the risk is abrogated compared with severe stenosis, with an ipsilateral stroke risk of 9.4% at 5 years. Other studies of patients with asymptomatic disease demonstrate the variability in stroke incidence. In the Veterans Affairs Cooperative Study (VACS) of patients with asymptomatic stenosis >50%, the risk of ipsilateral stroke at 4 years was 10.3% in those treated with medical therapy.7 Similar findings were noted by the asymptomatic carotid artery stenosis (ACAS) investigators who found a risk of ipsilateral stroke of 6.2% at 2.7 years of follow-up in patients with >60% stenosis.7 The risk of stroke provided above is indicative of older studies with medical therapy that predates the current era. In more contemporary studies with optimal medical therapy, the risk of ipsilateral stroke has been shown to be as low as 0.34% per year with a risk of ipsilateral TIA of 1.78% per year.8
Risk factors for carotid stenosis are similar to those for coronary artery disease (CAD), reflected in the fact that more than one-fifth of patients undergoing coronary artery bypass grafting (CABG) have >50% carotid stenosis.9Conversely, in patients with cerebral infarction, more than 50% have some degree of coronary stenosis, and more than one-fourth have coronary stenoses >50%.10 Material extracted from embolic protection devices (EPDs) after CAS reveal lipid vacuoles, foam cells, fibrin, and platelets, similar to that of coronary lesions. Increasing age results in greater risk of stroke or TIA in both men and women as well as across race.1 The relative risk of stroke is doubled among smokers and returns to baseline levels after 5 years of abstinence.11 Hypertension, diabetes mellitus, hyperlipidemia, and the metabolic syndrome all impart an increased risk.12–14
CAROTID AND ARCH ANATOMY
Defining aortic arch anatomy is an important part of carotid and cerebrovascular angiography and is necessary in planning a carotid intervention. The aortic arch is defined as type I, II, or III depending on the relationship of the innominate artery to the inner and outer aortic arch curvature(s) (Fig. 51.1). While the normal arch branching pattern consists of the innominate, left common carotid (LCC), and left subclavian (LSC) arteries (proximal to distal), there are a number of variants. In about one-fourth of patients, the LCC and innominate share a common origin, and in about one-sixth of patients, the LCC originates directly from the innominate artery. Both of these configurations are termed “bovine arch,” though in reality bear no resemblance to the arch of cattle.15 Other variations include an anomalous right subclavian artery that originates directly from the arch distal to the LSC artery, anomalous left vertebral artery originating directly from the arch, and a thyrocervical trunk originating from the aorta.
FIGURE 51.1 Classification of aortic arch type is based upon the relationship of the innominate artery to the inner and outer curvature of the arch. (Reproduced from Krishnaswamy A, Klein JP, Kapadia SR. Clinical cerebrovascular anatomy. Cath Cardiovasc Int. 2010;75:530–539, with permission from John Wiley and Sons.)
The common carotid artery bifurcates into the external and internal carotid arteries (ICAs) at the C3–C4 interspace, and is the most common site of carotid atherosclerosis. The external carotid artery courses anteriorly and supplies numerous important branches to the face and neck, which also serve as collaterals in the setting of severe ICA disease. The ICA is divided into the cervical, petrous, cavernous, and supraclinoid portions, and no branches arise from the cervical or petrous ICA. The supraclinoid portion of the ICA (carotid siphon) bifurcates into the middle cerebral artery (MCA) and anterior cerebral artery (ACA).
CLINICAL PRESENTATION
Carotid disease may be diagnosed incidentally during physical examination or by diagnostic testing, or as part of the workup of stroke or TIA. While carotid auscultation is a common and important part of a comprehensive cardiovascular physical examination, its sensitivity in patients with stenosis >60% is reported to be as low as 56%.16 Therefore, in high-risk patients, carotid ultrasound is recommended for risk stratification. Population screening is not recommended by the United States Preventive Services Task Force (USP-STF), however.17
TIA is defined as symptoms that resolve within 24 hours (most commonly within 30 minutes) and does not have associated acute imaging changes. Carotid-territory TIA or stroke can be reasonably elucidated from a detailed history and physical examination (Table 51.1). Aphasia, dysarthria, or visual symptoms such as ipsilateral amaurosis fugax or contralateral homonymous hemianopia may be present. Sensory and motor symptoms are typically contralateral.
TABLE
51.1 Stroke Syndromes Involving the Major Vascular Territories
MCA, middle cerebral artery; ACA, anterior cerebral artery; PCA, posterior cerebral artery.
DIAGNOSTIC TESTING
There are various imaging modalities used in the diagnosis of, and procedural planning for, carotid disease.
Carotid Ultrasound
Ultrasonography is the standard noninvasive test for the evaluation of carotid disease. Large studies utilizing carotid ultrasound with angiography as a gold standard have reported sensitivity and specificity of >95% in diagnosing angiographic stenosis >50%.18,19 Standard criteria for the diagnosis of carotid stenosis (the modified Stradness criteria) are listed in Table 51.2. It is important to note, however, that severe left ventricular (LV) dysfunction, severe aortic stenosis (AS), and significant common carotid stenosis can all spuriously decrease carotid velocities and therefore minimize the degree of stenosis calculated.
TABLE
51.2 Doppler Criteria for Diagnosis of Carotid Stenosis
PSV, proximal systolic velocity; ICA, internal carotid artery; CCA, common carotid artery.
Carotid Intima Media Thickness
Carotid intima media thickness (IMT) provides a measure of subclinical atherosclerosis and is usually measured in the common carotid artery. It is a measure of the thickness of the intima and media on two-dimensional (2-D) ultrasound imaging, normally increases with age, and is greater in men than women.20 Carotid IMT may be used for risk stratification purposes in patients without established atherosclerotic disease and intermediate probability as it has been associated with a higher risk of myocardial infarction (MI), stroke, and cardiovascular death.21–23
Computed Tomography Angiography
Computed tomography angiography (CTA) is increasingly used in the evaluation of the coronary and peripheral arteries. In a recent evaluation of CTA, investigators reported a sensitivity and specificity of 77% and 95%, respectively, for diagnosing severe carotid stenosis.24 One significant limitation in the accurate diagnosis of luminal narrowing is the presence of calcium blooming artifact. The diagnosis of moderate stenosis has lower accuracy (sensitivity 67%), similar to MRA in this setting.
Magnetic Resonance Angiography
Carotid imaging using MRA can be performed after gadolinium contrast administration or using time-of-flight (TOF) imaging without contrast. Unfortunately, noncontrast MRA may have poor sensitivity and specificity due to the lengthy time of acquisition (10 minutes), which increases artifact. On the other hand, gadolinium MRA has reasonable sensitivity (95%) and specificity (92%) for diagnosing severe stenosis (>70%).25 Similar to CTA, diagnosis of moderate stenosis is poor (sensitivity 66%).
Angiography
Established as the gold standard for evaluating carotid stenosis, angiography should be performed using digital subtraction angiography (DSA) to “remove” the bones and soft tissues for better visualization of the arteries. Angiography provides highresolution images, allows an analysis of plaque quality (i.e., calcification, ulceration), and enables the operator to evaluate the arch, neck vessels, intracerebral circulation, and collateral filling at the same time. This method is not usually a first-line test given the historically reported risk of transient (1.3%) or permanent (0.6%) neurologic complications.26,27 Notably, a more contemporary series of cerebrovascular angiography showed a much lower rate of complications, with 0.06% transient neurologic deficits and 0.2% iatrogenic dissection, though this series included no arch aortograms and only a small percentage of patients with ischemic cerebrovascular disease.28
MEDICAL TREATMENT
Primary and secondary prevention of carotid atherosclerosis includes risk factor modification and management. The use of CAS or CEA may be relevant in both situations, and are discussed further below.
Antiplatelet Therapy
Historically, aspirin is the cornerstone of antiplatelet therapy. In the Antithrombotic Trialist Collaboration’s meta-analysis of 287 randomized trials enrolling >200,000 patients, they demonstrated a 25% reduction in nonfatal stroke and a 30% reduction in fatal or nonfatal ischemic stroke.29 Additionally, low-doses of aspirin (75 to 150 mg) were just as effective as higher doses, though with the caveat that this conclusion was based on less robust data. It should be noted, though, that the benefit of aspirin has been noted mostly in patients considered to be at high risk. Conversely, patients at low-risk for events have greater potential for harm due to bleeding. As a result, the American College of Cardiology/American Stroke Association (ACC/ASA) guidelines provide a Class I recommendation for aspirin in patients for whom the benefits are likely to outweigh the risks (10-year risk 6% to 10%), though the recommendation is largely based on a reduction in all cardiovascular events and not specifically stroke alone.17 Use of aspirin in women specifically is noted as a Class IIa indication, again for those in whom ischemic stroke risk reduction outweighs the risk of gastrointestinal bleeding or hemorrhagic stroke.17 Recent trials have not convincingly shown that aspirin decreases the risk of first stroke in patients with diabetes (and without CAD), but have produced trends toward benefit. However, professional societies have found it difficult to completely abandon the use of aspirin in this setting. The ACC/ASA guidelines therefore provide a Class IIb recommendation for the use of aspirin in the primary prevention of stroke in diabetics at “high CV risk” with the caveat that the benefits “remain unclear.”17,30,31 All patients with documented carotid disease should receive aspirin (or alternative regimen below).
Clopidogrel is an antiplatelet agent that irreversibly binds the P2Y12 subunit of the ADP receptor, blocking GP IIb/IIIA-mediated platelet aggregation. In the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial of patients with cardiovascular disease, clopidogrel demonstrated an 8.7% relative risk reduction (RRR) for the primary outcome of stroke, MI, or death.32 There was a trend toward benefit (RRR 7.3%, p = 0.26) in patients with a history of stroke. On the basis of this and other studies, clopidogrel has been given an ACC/ASA Class I recommendation as an alternative agent to aspirin for secondary prevention in patients with a history of TIA or stroke.33
While dual antiplatelet therapy (DAT) with aspirin and clopidogrel is often used in patients after coronary artery stenting, two large studies have not found a benefit in patients with stroke. In both the MATCH (Management of Atherothrombosis with Clopidogrel in High-Risk Patients with Recent Transient Ischaemic Attack or Ischemic Stroke) and CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trials, DAT did not significantly decrease stroke outcomes, but did result in a significantly increased bleeding.34,35 The ACC/ASA guidelines therefore provide a Class III recommendation (not recommended) for the use of DAT for secondary prevention of stroke.33
Dipyridamole (DP) is an adenosine deaminase (ADA) and phosphodiesterase (PDE) inhibitor, which results in an increased concentration of cyclic AMP, adenosine, and adenine nucleotides; this inhibits platelet aggregation and causes vasodilation. Large studies using ASA and DP in patients with stroke have found a significant benefit to the use of combination therapy over monotherapy.36,37 Therefore, the
ACC/ASA guidelines provide a Class I recommendation for ASA/DP combination therapy for patients with TIA/stroke, and suggest its use over aspirin monotherapy.33
Anticoagulant Therapy
While anticoagulation with vitamin K antagonists is standard therapy for patients with cardioembolic source of TIA or stroke, there has been no suggestion of benefit over aspirin in patients with noncardioembolic stroke. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) randomized patients to warfarin (goal international normalized ratio (INR) 3.0 to 4.0) versus aspirin for secondary prevention.38 Patients receiving warfarin had more than double the adverse events, mostly attributed to bleeding complications. The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) investigators made a similar randomization though with a more conservative INR goal (2.0 to 3.0) but were forced to terminate the trial early due to an almost threefold increase in major hemorrhage.39 Ultimately, due to complications of bleeding and a lack of benefit for patients with atherosclerotic disease, anticoagulation is reserved for patients with a cardioembolic source of stroke or hypercoagulability disorder and is otherwise not indicated for the routine secondary prevention of TIA or stroke.
Antihypertensive Therapy
A large percentage of the US population has hypertension, and numerous studies have documented a 30% to 40% reduction in stroke with blood pressure control.40 While many studies using individual antihypertensive regimens (thiazides, beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, etc.) have shown a reduction in stroke, there is a paucity of data to recommend one specific therapy over another. The treatment of hypertension for both primary and secondary prevention has been given a Class I recommendation by the ACC/ASA.17,33 For primary prevention in patients, treatment to a goal blood pressure (BP) <140/90 mm Hg is recommended, with a goal BP <130/80 in patients with diabetes or renal disease (Class I).17 Secondary prevention guidelines support a goal BP of <120/80 mm Hg with a Class IIa recommendation.33 All of these recommendations are made on the basis of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). While no specific agents are recommended for either group due to the small number of trials and limited comparisons, diuretics or the combination of diuretics and angiotensin-converting enzyme inhibitor (ACEi) are provided a Class IIa recommendation (for secondary prevention).33 The use of ACEi or angiotensin receptor blockers (ARBs) is given a Class I recommendation for patients with diabetes.17,33
Antihyperlipidemic Therapy
Statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) have become the mainstay of antihyperlipidemic treatment for the primary and secondary prevention of cardiovascular events. Studies of statin use in patients with CAD have shown a reduction not only in coronary events but also in the risk of first-time TIA and stroke. In one of the first trials of statin therapy in patients with a history of CAD, the Scandinavian Simvastatin Survival Study (4S), patients had an approximately 30% RRR in stroke or TIA.41 Studies of statin use in patients without established cardiovascular disease have also shown promising reductions in the risk of first stroke. For instance, use of rosuvastatin among a large group of healthy men and women with elevated C-reactive protein in the JUPITER trial provided an almost 50% RRR in stroke.42 The benefits of statin therapy in reducing stroke among patients with and without CAD was also demonstrated in a meta-analysis of >200,000 patients showing an RR of 0.75 in patients with CAD and 0.77 in patients without CAD.43 Ultimately, the use of statin therapy for the primary prevention of ischemic stroke is based upon the National Cholesterol Education Program (NCEP) recommendations (Table 51.3), and is given a Class I recommendation.
TABLE
51.3 NCEP Recommendations for Statin Therapy for Primary Stroke Prevention
From Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke. A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2011;42(2):517–584, with permission.
RECOMMENDATION
Statin use for the secondary prevention of stroke or TIA is well-established, largely on the basis of the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial.17,44 Approximately 5,000 patients with stroke (and without known CAD) were randomized to atorvastatin 80 mg daily versus placebo and followed for almost 5 years. The treatment group demonstrated an HR of 0.84 in the primary outcome of fatal or nonfatal stroke, a difference that was more pronounced in the group with carotid stenosis (HR 0.67). The use of statin treatment as secondary prevention is therefore given a Class I recommendation in the AHA/ASA guidelines, even for patients without CAD.33 Treatment to a goal LDL <70 mg/dL can be considered (Class IIa).33
CAROTID ENDARTERECTOMY
Endarterectomy of the carotid artery was first performed in 1953 by Dr. Michael DeBakey. Since then, numerous large trials have been performed to investigate the use of CEA in patients with prior TIA/stroke. The North American Symptomatic Carotid Endarterectomy Trial Collaborators (NAS-CET) performed a randomized, prospective trial of CEA versus medical therapy among patients with symptomatic carotid stenosis.45 Over a 2-year follow-up, CEA resulted in a significantly lower risk of stroke (9% vs. 26%, p <0.001) and a lower risk of major or fatal stroke (2.5% vs. 13.1%, p <0.001) in 659 patients with 70% to 99% stenosis. Among 2,216 patients with symptoms and moderate stenosis (50% to 69%), 5-year follow-up showed benefit also to CEA but to a lesser degree (15.7% vs. 22.2%, p = 0.045). Among 6,092 patients with symptomatic disease in a pooled analysis of the three major randomized trials (NASCET, European Carotid Surgery Trial [ECST], and VACS), CEA provided a 48% reduction from stroke or death in patients with 70% to 99% stenosis (RR 0.52, 95% CI 0.40 to 0.64), and a 28% reduction in patients with 50% to 69% stenosis (RR 0.72, CI 0.58 to 0.86).46 Patients with <50% stenosis did not benefit from CEA. Given the data gleaned from randomized trials, CEA is given a Class I recommendation for patients with symptomatic stenosis >50% and a perioperative morbidity and mortality risk of <6%.33 CEA is not indicated (Class III) for patients with stenosis <50%.
The ACAS, the VA Trial, and the Asymptomatic Carotid Surgery Trial (ACST) are the three major trials of CEA in patients with asymptomatic carotid stenosis. In ACAS, 1,662 patients were randomized to CEA versus medical therapy. CEA was performed for patients with >60% stenosis as gauged by angiography. Surgery was found to provide a significant decrease in the risk of ipsilateral stroke, perioperative stroke, or death (5.1% vs. 11%, p = 0.004) at a calculated aggregate follow-up of 5-years.47 The ACST assigned 3,120 patients with >70% stenosis (on ultrasound) to CEA or medical therapy (“deferred” CEA until indicated). The net 5 year risk for all strokes or perioperative death was significantly reduced in the CEA group (6.4% vs. 11.8%, p <0.001), including the 3.1% risk of 30-day stroke or death with CEA.48It should be noted, however, that this overall benefit was delayed. As shown in Figure 51.2, patients receiving CEA had a worse outcome until almost 2 years postsurgery, implying that patient selection should also account for comorbidities and life expectancy. Largely on the basis of these two trials and the VA trial, CEA is given a Class IIa recommendation by the AHA/ASA for asymptomatic patients with >70% stenosis by ultrasound and >60% stenosis by angiography and an estimated perioperative event rate of <3%.17 A thorough assessment of risks and life expectancy, as well as an educated conversation with patients regarding the same, is imperative (Class I recommendation). It should be noted, also, that a major criticism of the large trials on which CEA was established (NASCET, ECST, ACAS, etc.) utilized medical therapy that is suboptimal based on today’s standards, and may therefore overestimate the benefits of CEA.17 For instance, a recent small study of patients with asymptomatic > 50% stenosis on contemporary medical therapy had an approximately 6% risk of ischemic event (stroke or TIA) at 3 years.8 Newer trials are therefore warranted to test the benefits of CEA in the asymptomatic population (Tables 51.4 and 51.5).
FIGURE 51.2 5-year event-free survival (free of all strokes or death) with immediate versus deferred CEA shows a benefit to CEA only after 2 years due to the 30-day risk of complications with surgery. (Reprinted from The Lancet, 363, Halliday A, et al. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial, 1491–1502, © 2004, with permission from Elsevier.)
TABLE
51.4 Guideline Recommendations for Revascularization in Patients with Carotid Stenosis
CEA, carotid endarterectomy; CAS, carotid artery stenting.
TABLE
51.5 Comparison of Risks and Benefits of CEA and CAS
Aksoy O, Kapadia SR, Bajzer C, Clark WM, Shishehbor MH. Carotid stenting vs surgery: Parsing the risk of stroke and MI. Cleve Clin J Med 2010; 77:892–902. Reprinted with permission. Copyright © 2010 Cleveland Clinic Foundation. All rights reserved.
CAROTID ARTERY STENTING
Percutaneous transluminal angioplasty (PTA) of the carotid artery in humans was first reported in 1980. Since then, there has been a proliferation of stent technology to address issues of vessel recoil and dissection after balloon dilation and development of EPDs to reduce the risk of periprocedural embolic complications. Both are considered to represent the standard of care in the current era of CAS.
The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial was the first randomized controlled trial comparing emboli-protected CAS to CEA.49 The 334 patients enrolled were either asymptomatic with ≥80% stenosis by ultrasound or symptomatic with ≥50% stenosis. All patients were considered to have high risk for surgery, and approximately 70% were asymptomatic. The primary end point of major adverse cardiovascular events (MACE) (which included death, stroke, or MI within 30 days of the procedure plus death from neurologic causes or ipsilateral stroke up to 1 year) was lower in the CAS group (12.2% vs. 20.1%, p = 0.05). At 3-year follow-up, the prespecified major secondary endpoint of MACE (death, stroke, or MI within 30 days of the procedure or death or ipsilateral stroke between 31 and 1,080 days) occurred in 24.6% of the protected CAS group and 26.9% of the CEA group (p = 0.71).50
The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) was recently published and randomized roughly equivalent numbers of symptomatic (53%) and asymptomatic (47%) patients to protected CAS or CEA.51 Among the 2,502 patients enrolled, the primary endpoint (any periprocedural stroke, MI, or death or postprocedural ipsilateral stroke) at 4 years was not significantly different between the CAS and CEA groups (5.2% vs. 4.5%, p = 0.38). Notably, though, the risk of stroke was significantly higher with CAS (4.1% vs. 2.3%, p = 0.01), and the risk of MI was significantly lower (1.1% vs. 2.3%, p = 0.03). While these differences resulted in an overall similar primary outcome for the two groups, quality-of-life analysis at 1-year showed that stroke resulted in a large adverse effect than did MI. There was a suggestion in subgroup analysis that CAS tended to show greater efficacy in patients <70 years.
In contrast to SAPPHIRE and CREST, SPACE (the Stent- Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients trial), EVA-3S (the Endarterectomy Versus Stenting in Patients with Symptomatic Severe Carotid Stenosis trial), and ICSS (the International Carotid Stenting Study) all showed CAS to be inferior to CEA. All studies were in symptomatic patients and were conducted in Europe. Collectively, a number of criticisms have been raised surrounding these trials. These include lack of operator experience and minimal use of EPDs.
The current data on CAS have resulted in a Class IIb recommendation by the ACC/AHA for “highly selected” patients with asymptomatic carotid stenosis. The U.S. FDA does not provide reimbursement for CAS in these patients outside of clinical trial enrollment. Conversely, in symptomatic patients with stenosis >70% by ultrasound or >50% by angiography, CAS is indicated (Class I) as an alternative to CEA for patients with an average or low risk of complications with CAS.33 In patients with severe symptomatic stenosis and anatomic considerations that make CEA technically challenging or comorbid conditions that result in high surgical risk, CAS may be considered (Class IIb) but is less highly recommended (likely due to the significant coexisting conditions that increase overall morbidity and mortality in this group of patients).33 These factors include New York Heart Association (NYHA) III/IV heart failure, Class III/IV angina, left main coronary disease, two-vessel CAD, left ventricular ejection fraction <30%, recent MI, severe lung or renal disease, prior neck operation or irradiation, restenosis after CEA, contralateral carotid occlusion, tracheostomy, or surgically inaccessible lesions.
CONCLUSIONS
Stroke is a leading cause of morbidity and mortality, and carotid atherosclerotic disease is a common etiology of ischemic cerebrovascular events. Risk factors for the development of carotid disease include the usual causes of atherosclerosis such as hypertension, age, and diabetes, as well as tobacco use, renal disease, and others. The diagnosis of carotid stenosis should be considered in patients at high risk for vascular disease as well as patients who have suffered a TIA or stroke. The diagnosis is usually made using ultrasound, though CTA, MRA, or conventional angiography may play a role in certain situations. The management of carotid disease includes antihypertensive, antihyperlipi- demic, and antiplatelet therapies. The use of CEA or CAS for revascularization depends on a myriad of factors including the degree of stenosis, symptom status, expected procedural risk, comorbidities, and life expectancy.
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QUESTIONS AND ANSWERS
Questions
1. Which of the following has no proven benefits in reducing the risk of a first stroke in patients with diabetes mellitus?
a. Blood pressure control
b. Aspirin
c. Statin therapy
d. Blood pressure control and statin therapy
2. Which of the following antiplatelet regimens is not recommended in patients with a history of transient ischemic attack (TIA)/stroke?
a. Aspirin plus dipyridamole (DP)
b. Clopidogrel
c. Aspirin alone
d. Aspirin plus clopidogrel
3. A 57-year-old gentleman is referred to your clinic for management after his primary medical doctor auscultated a right carotid bruit. He exercises regularly and “watches what he eats.” On your exam, his blood pressure is 155/95 mm Hg and heart rate 70 beats/min (bpm). Laboratory testing reveals a serum LDL of 168 mg/dL and HDL of 50 mg/dL, a fasting blood glucose of 85, and normal GFR. Which of the following is recommended to decrease the risk of a first stroke in this patient?
a. Blood pressure control to goal BP <140/90 mm Hg
b. Statin therapy to goal LDL <160 mg/dL
c. Statin therapy to goal LDL <130 mg/dL
d. Blood pressure control to goal BP <140/90 mm Hg and statin therapy to goal LDL <160 mg/dL
e. Blood pressure control to goal BP <140/90 mm Hg and statin therapy to goal LDL <130 mg/dL
4. For the patient above, what would be the next step in management?
a. Duplex carotid ultrasonography
b. Carotid angiography
c. Computed tomography angiography (CTA)
d. No further testing is necessary
5. The patient above undergoes carotid ultrasound testing that reveals a right carotid stenosis of 80% to 99%. What is the appropriate management?
a. Continued medical therapy and surveillance for development of symptoms
b. Referral for carotid endarterectomy (CEA)
c. Referral for carotid artery stenting (CAS)
d. All of the choices
6. Which of the following diagnostic modalities for assessing carotid disease has the lowest sensitivity for detecting severe stenosis?
a. Carotid-CTA
b. Contrast-enhanced magnetic resonance angiography (MRA)
c. Invasive carotid digital subtraction angiography (DSA)
d. Carotid ultrasonography
7. Which of the following favor CAS over CEA?
a. Risk of periprocedural myocardial infarction (MI)
b. Risk of periprocedural stroke
c. Preferred procedure for restenosis after endarterectomy
d. Risk of periprocedural MI and preferred procedure for restenosis after endarterectomy
8. A 75-year-old man with hypertension, previous coronary artery bypass grafting (CABG), and atrial fibrillation presents with new onset weakness and numbness of the left face and arm. Which vascular territory is likely to be compromised?
a. Right anterior cerebral artery (ACA)
b. Right vertebral artery
c. Right middle cerebral artery (MCA)
d. ACA-MCA watershed infarction
Answers
1. Answer B: Recent trials have not convincingly shown that aspirin decreases the risk of first stroke in patients with diabetes (and without CAD), but have produced trends toward benefit. However, professional societies have found it difficult to completely abandon the use of aspirin in this setting. The ACC/ASA guidelines therefore provide a Class lib recommendation for the use of aspirin in the primary prevention of stroke in diabetics at “high CV risk” with the caveat that the benefits “remain unclear.” The treatment of hypertension for primary prevention has been given a Class I recommendation by the ACC/ASA, and the use of ACEi or ARBs is given a Class I recommendation for patients with diabetes. The goals of statin therapy for the primary prevention of ischemic stroke is based upon the National Cholesterol Education Program (NCEP) recommendations, and is given a Class I recommendation.
2. Answer D: The ACC/ASA guidelines provide a Class I recommendation for aspirin plus dipyridamole (ASA/DP) combination therapy for patients with TIA/stroke. The use of the combination is suggested over aspirin monotherapy, though monotherapy is reasonable if clinical considerations preclude the use of the combination regimen. Clopidogrel has been given an ACC/ASA Class I recommendation as an alternative agent to aspirin for secondary prevention. Due to large studies that showed an increased risk of bleeding with ASA/clopidogrel combination therapy, and no significant decrease in the risk of stroke in comparison to aspirin alone, this combination has been given a Class III (not recommended) designation.
3. Answer E: The patient has two CHD risk factors (age and hypertension) in addition to hyperlipidemia. The treatment of hypertension substantially reduces the risk of a first stroke, and treatment to goal BP <140/90 mm Hg (<130/80 in patients with diabetes or renal disease) is given a Class I recommendation based on the JNC-7. With regard to lipid management, this patient meets criteria for a goal LDL <130 mg/dL based on NCEP guidelines, with the use of statin therapy (ACC/ASA Class I recommendation) as necessary in addition to lifestyle modifications. This patient actually has a Framingham 10 year risk of 12%, so would qualify for the optional treatment goal of LDL <100 mg/dL.
4. Answer A: This patient is in an intermediate-risk category given his risk factors for cardiovascular disease as well as an auscultory bruit on exam. He would therefore merit further investigation to determine the severity of disease. Carotid ultrasound has been validated through large studies, and in comparison to the “gold standard” of angiography has a sensitivity of >95% for the diagnosis of carotid stenosis >50%. Carotid angiography is not indicated as a first-line study given its invasive nature and the risk of transient (1.3%) or permanent (0.6%) neurologic complications. CT angiography has a lower sensitivity than ultrasound (77% for severe stenosis, 67% for moderate stenosis). In the absence of factors that might make interpretation of ultrasound examination less accurate (i.e., severe LV dysfunction or severe aortic stenosis [AS]), ultrasound would therefore be preferred.
5. Answer D: The patient has severe but asymptomatic carotid stenosis. Therefore, medical management or revascularization (with medical management) would be reasonable. CEA may be beneficial over medical therapy alone if the procedure can be completed with a <3% complication rate and the patient’s life expectancy exceeds 3 years (as expected in this patient) (ACC/ASA Class IIa recommendation). The historic trials on which this benefit is based, however, are dated and may therefore overestimate the benefits of CEA for reducing stroke risk over contemporary medical therapies. CAS has compared favorably to CEA in this patient population, but trades a lower rate of procedural MI for a higher rate of procedural stroke (ACC/ASA Class IIb recommendation). Therefore, a detailed conversation with the patient is imperative to discuss the choice of procedure as well as the risks/benefits of a procedure in comparison to medical therapy alone. Of note, CAS in asymptomatic patients is reimbursed by CMS only under the auspices of a clinical trial.
6. Answer A: CT angiography has been shown in numerous studies to have poor sensitivity in the evaluation of carotid disease, with a sensitivity of 77% for severe stenosis and 67% for moderate stenosis. Calcium blooming artifact is a significant issue. MRA without contrast has poor sensitivity, but gadolinium-enhanced MRA has good sensitivity (95%) and specificity (92%) for diagnosing severe stenosis (>70%). Carotid angiography is considered the “gold standard” of diagnosis for carotid stenosis. Carotid ultrasound has been validated through large studies, and in comparison to angiography has a sensitivity of >95% for the diagnosis of carotid stenosis >50%.
7. Answer D: Numerous studies comparing CEA and CAS have shown a similar rate of overall clinical outcomes but increased risk of stroke with CAS and increased risk of MI with CEA. In patients with restenosis after CEA, stenting is the preferred treatment.
8. Answer C: Infarction of the right MCA territory results in contralateral motor and sensory deficits predominantly affecting the face and arms. Compromise of the right ACA would result in contralateral motor and sensory deficits predominantly affecting the legs. ACA–MCA watershed infarcts may present with proximal greater than distal arm and leg weakness. Furthermore, watershed infarcts generally present in settings of hypoperfusion (i.e., hypotension), while MCA infarcts are the most common location for cardioembolic stroke (which is likely in this patient with a history of CABG, hypertension, and AFib).