Role of Duplex Ultrasound in Carotid Screening

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Faisal Aziz, Robert P. Scissons, and Anthony J. Comerota

Abstract

Screening programs designed to identify disease in the general public have proliferated in recent years, and increased stroke awareness has resulted in both free and for-profit screening programs for carotid disease being offered to the public. This chapter evaluates the effectiveness of screening for carotid artery disease, which by definition means identifying patients with asymptomatic internal carotid disease. A literature review of the history of carotid screening for both general and high-risk populations was undertaken, and the costeffectiveness of screening programs analyzed. Despite the increased interest related to patients with asymptomatic carotid artery stenosis, screening for carotid artery disease is difficult to justify as the prevalence of asymptomatic carotid artery stenosis and risk of subsequent ipsilateral stroke are low in the general public. Moreover, the number of patients needed to screen in order to prevent one stroke is excessive. At present, there are no data supporting screening for asymptomatic carotid disease in individuals appropriately treated for cardiovascular risk reduction. It is unlikely that screening for carotid artery disease will improve patient care or be cost-effective. Keywords

Asymptomatic carotid artery disease • Doppler ultrasonography • Screening cost-effectiveness • Stroke prevention

F. Aziz, M.D., RVT, RPVI Department of Surgery, Section of Vascular Surgery, Penn State Hershey College of Medicine, Hershey, PA, USA Jobst Vascular Institute, The Toledo Hospital, 2109 Hughes Dr, Suite 400, Toledo, OH 43606, USA R.P. Scissons, RVT, FSVU Jobst Vascular Laboratory, Jobst Vascular Institute, The Toledo Hospital, Toledo, OH, USA A.J. Comerota, M.D., RVT, FACS, FACC (*) Department of Surgery, Section of Vascular Surgery, University of Michigan, Ann Arbor, MI, USA Jobst Vascular Institute, The Toledo Hospital, 2109 Hughes Dr, Suite 400, Toledo, OH 43606, USA e-mail: [email protected] A.F. AbuRahma, D.F. Bandyk (eds.), Noninvasive Vascular Diagnosis, DOI 10.1007/978-1-4471-4005-4_12, © Springer-Verlag London 2013

Introduction The Asymptomatic Carotid Atherosclerosis Study (ACAS) [1] was the first randomized controlled trial to show that surgical treatment offered to asymptomatic patients with highgrade carotid artery stenosis reduces the risk of subsequent stroke. Other randomized trials subsequently confirmed those findings. Although surgery for symptomatic carotid artery stenosis has become standard treatment for appropriate lesions, enthusiasm for the surgical management of asymptomatic carotid artery stenosis has also increased. This enthusiasm has resulted in a significant increase in the number of asymptomatic patients undergoing carotid revascularization procedures. According to a survey, carotid endarterectomy (CEA) for asymptomatic stenosis accounts for more than 90% of all carotid artery surgeries. The purpose of this chapter is to evaluate the effectiveness of screening for 173

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carotid artery disease, which by definition means identifying patients with asymptomatic carotid bifurcation disease. Stroke is associated with serious morbidity and mortality. Eighty percent of strokes are ischemic, and 20% of these are due to large-artery stenosis [2]. Carotid artery duplex is highly sensitive and specific to diagnose internal carotid artery stenosis. The threshold of peak systolic velocity of >130 cm/s is associated with sensitivity of 98% and specificity of 88% in identification of angiographic stenosis of >50%. For diagnosis of angiographic stenosis of >70%, a peak systolic velocity >200 cm/s has a sensitivity of 90% and a specificity of 94% [3]. Carotid artery duplex is the tool for screening asymptomatic people to detect internal carotid stenosis, but to justify its use, one should show that the identification and treatment of an asymptomatic carotid lesion reduces the incidence of stroke. Therefore, it is important to evaluate whether the prevalence, natural history, and current treatment options for asymptomatic carotid artery stenosis support a generalized screening program for the public. There have been no randomized controlled trials to answer this question. Consequently, one needs to determine how many asymptomatic people have to be screened and treated specifically for the lesion found in order to avoid one stroke. We reviewed the literature on carotid screening for general and high-risk populations and the cost-effectiveness of screening programs. This discussion has become more relevant due to increased public awareness, often resulting from free blood pressure and cholesterol checks offered by pharmacies around the country. Moreover, several agencies are offering screening duplex ultrasounds for detecting peripheral arterial disease, carotid artery stenosis, and abdominal aortic aneurysms. Most people who have these tests are older, and many are unaware of the importance of these tests and their findings. Therefore, it is crucial to determine if such screening programs are necessary and, if so, should be offered by accredited vascular laboratories, which can educate the patients about the results and the importance of their findings.

Potential Burden of Stroke Resulting from Carotid Artery Stenosis Stroke is the third leading cause of death and the most common cause of long-term disability in the United States [4]. Each year, about 700,000 people suffer a new or a recurrent stroke on average; every 45 s, someone in the United States has a stroke, and every 3 min, someone dies of a stroke. Stroke accounted for about 1 of every 15 deaths in the United States in 2003. Men’s stroke incidence rates are 1.25 times greater than women’s. Because women live longer than men, more women than men die of stroke every year. Women accounted for 61% of stroke deaths in the United States [4].

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Stroke is a life-changing event. Kelly-Hayes et al. [5] reviewed outcomes from the Framingham Study and found that 12% of those who survive a first stroke or TIA have another within the first year. Twenty-two percent of men and 25% of women who have a stroke die within a year. This percentage is higher for patients who are 65 and older. Approximately 50–70% of stroke survivors regain functional independence, but 15–30% are permanently disabled and 20% require institutionalized care at 3 months after onset. The same data show that among patients who were at least 65 years old, 50% had residual hemiparesis and 26% were institutionalized 6 months after their stroke. Therefore, in light of the devastating consequences of stroke, prevention is desirable by health care professionals, organizations, and society in general. One approach is to offer appropriate screening tests, assuming the causative lesion can be identified and subsequently treated.

Natural History of Asymptomatic Carotid Artery Stenosis The occurrence of stroke and death resulting from asymptomatic carotid artery stenosis is proportional to the prevalence and prognosis of untreated disease. Population-based studies using duplex scanning have shown that the prevalence of ³50% carotid stenosis ranges between 2% and 8%, and those with asymptomatic carotid artery stenosis of 80% or more is between 1% and 2% [6–10]. The cost-effectiveness of carotid screening depends upon the natural history of the asymptomatic carotid lesion. The low incidence of asymptomatic carotid artery stenosis has implications for carotid artery screening programs. Positive predictive value of any screening modality will change with the prevalence of disease in the tested population [11]. Assuming that duplex scanning for asymptomatic carotid artery stenosis has sensitivity and specificity of 95%, positive predictive value of duplex scanning for a carotid artery stenosis of more than 50% would be approximately 50%, and the positive predictive value of duplex scanning for a carotid stenosis of more than 80% or greater would be 16% [12]. However, the actual sensitivity and specificity of carotid duplex is less than 95%, therefore resulting in lower positive predictive values, even when evaluated in a highly selected patient population [13]. Therefore, with low prevalence in general population, the positive predictive value of a screening study like carotid duplex is severely diminished. Norris et al. [14] performed a natural history study of 696 patients and demonstrated that the annual risk of ipsilateral stroke was 2.5% for patients with asymptomatic carotid artery stenosis of more than 75%. Lesser degrees of stenosis were associated with a lower annual stroke rate (1.3%).

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Role of Duplex Ultrasound in Carotid Screening

The European Carotid Surgery Trial (ECST) [15] showed that for patients with asymptomatic carotid artery stenosis of 70% or more, the 3-year risk of ipsilateral stroke was 5.7% (annual risk of stroke 1.9%). For lesser degrees of asymptomatic carotid artery stenosis, the 3-year risk of stroke was 2.1% (annual risk of stroke 0.7%). The ACAS study found that patients with an asymptomatic carotid artery stenosis ³60% who were treated medically had an annual rate of 2.12% [1]. In the medical arm of the Veterans Administration trial [16], the ipsilateral stroke rate was 9.4% at 47.9 months for patients with asymptomatic carotid artery stenosis of more than 50% (annual risk of stroke = 2.36%). To summarize, the average annual risk of stroke from asymptomatic carotid artery stenosis of 50% or greater is approximately 2–3% per year. Taking into account the low prevalence of asymptomatic carotid artery stenosis in the general public, an individual would have less than 0.16% risk per year of stroke or death from undetected asymptomatic carotid artery stenosis of 50% or greater, and a 0.06% risk from asymptomatic carotid artery stenosis of 80% or greater [17]. Sleight et al. [18] reviewed the long-term outcomes for patients enrolled in the medical management cohort of ECST. They excluded symptomatic patients and short-listed 219 patients who have had serial carotid duplex ultrasounds. They stratified patients based on their baseline carotid stenosis into three groups: 15–49% (n = 2), 50–79% (n = 110), and 80–99% (n = 107). At the end of 4-year follow-up, 31 patients regressed to a lower group, 148 remained in the same group, and 37 patients progressed by one group and 3 patients by two categories. These data showed that for patients undergoing medical management for asymptomatic carotid artery stenosis, the mean carotid stenosis does not change over 4 years. Nehler et al. [19] identified 263 patients with 434 asymptomatic 60%. None of the patients became symptomatic. Clinical risk factors associated with progression to >60% stenosis included elevated systolic blood pressure and decreased ankle-brachial index (p = 0.05). The life table-determined rate of freedom from progression to >60% stenosis was 94% at 4 years for asymptomatic internal carotid artery lesions that had initial peak systolic velocity less than 175 cm/s compared to 14% at 3 years for lesions that had initial peak systolic velocities >175 cm/s. This study shows that patients who are at greatest risk of early progression of carotid atherosclerosis are those who have systolic velocities higher than 175 cm/s. Rockman et al. [20] retrospectively reviewed the records of 282 asymptomatic internal carotid arteries with moderate stenosis (50–79%). Seventeen percent of internal carotid arteries demonstrated progression over 5 years. Estimated

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cumulative rates for progression of stenosis at 1, 3, and 5 years were 4.9%, 16.7%, and 26.5%, respectively. New ipsilateral strokes occurred in 3.8% and new ipsilateral transient ischemic attacks in 5.9% of patients. Arteries that progressed to >80% stenosis were more likely to have caused strokes than those that remained between 50% and 70% (10.4% vs. 2.1%, p < 0.02). Arteries that were unchanged, or stable, in the degree of stenosis were more likely to remain asymptomatic than those that progressed (92.7% vs. 62.5%, p < 0.001). The authors concluded that the only factor that appeared to predict increased risk for future stroke is progression of stenosis. Mansour et al. [21] reviewed outcomes in 344 patients (458 internal carotid arteries) with moderate carotid artery stenosis (50–79%). Life table analysis showed that the annual rate of ipsilateral neurologic events was 8.1% and the annual risk of stroke was 2.1%. Disease progression to 80–99% stenosis or occlusion occurred in 15.5% of arteries. The internal carotid arteries that showed evidence of disease progression had a significantly higher initial peak systolic velocity (251 vs. 190 cm/s, p < 0.0001) and end-diastolic velocity (74 vs. 52 cm/s, p < 0.0001). A greater amount of disease at baseline predicted progression. Muluk et al. [22] followed 1,701 carotid arteries in 1,004 patients for a mean follow-up of 28 months and found that the risk of progression of internal carotid artery stenosis increased steadily over time. The four most important variables that affected the progression were baseline ipsilateral internal carotid artery (ICA) stenosis of >50% (RR 3.34), baseline ipsilateral external carotid artery stenosis of >50% (RR 1.51), baseline contralateral ICA stenosis of >50% (RR 1.41), and systolic blood pressure >160 mmHg (RR 1.37). Ipsilateral neurologic ischemic events (strokes/TIAs) occurred in association with 14% of carotid arteries. Garvey et al. [23] performed prospective serial duplex scan surveillance of 1,470 carotid arteries in 905 asymptomatic patients during a 10-year period, with an average followup interval of 29 months. They identified six significant predictors of progression: age, sex, systolic blood pressure, pulse pressure, total cholesterol, and HDL. Multivariate analysis showed that only pulse pressure and HDL remained as significant independent predictors of stenosis progression. The risk ratio of 10 mmHg rise in pulse pressure was 1.12, and the risk ratio of 10 mg/dl decrease in HDL was 1.20. Shanik et al. [24] reported stenosis progression in 259 carotids over 96 months, with a mean follow-up of 48 months. Thirty-five of 96 (36%) arteries with mild stenosis showed progression, 21 developed 50–79% stenosis, 12 progressed to greater than 80% stenosis, and two progressed to carotid occlusion. Only two of these patients had a stroke. Ellis et al. [25] reported overall progression of 3.4% in 1,034 arteries with less than 50% stenosis at mean follow-up of 20 months.

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All of the studies mentioned in this section were performed 10–22 years ago, which raises the question as to whether their observations are valid today, as the medical management of patients with atherosclerosis has changed dramatically. Proper platelet inhibition, more aggressive control of blood pressure, and the use of statins have substantially reduced neurologic events in both symptomatic and asymptomatic patients. A number of important observations need to be recognized. The first is that 97% of carotid etiology strokes occur in patients with symptomatic carotid disease [26]. If one can ensure that all individuals with a 60–99% asymptomatic carotid stenosis can be identified and treated with either CEA or carotid angioplasty and stenting with a procedural risk of 2.3% (ACAS procedure risk), it will do little to reduce the overall burden of stroke [26]. An important question to address when evaluating the issue of screening for carotid artery disease is whether the risk of stroke from asymptomatic disease is changing. The seminal studies (ACAS, ACST) reported results of medical treatment of patients nearly 20 years ago. Is it appropriate to equate present-day cardiovascular risk to observations made 20 or more years ago? The answer is a decisive “no.” Even in the ACAS and ACST studies, there was no relationship of the degree of asymptomatic carotid stenosis to subsequent stroke, and there was no benefit to women who underwent CEA versus medical treatment. An important issue that needs to be addressed when carotid screening is being considered is: Has the risk of stroke from carotid artery disease decreased in the last 15–20 years? McPhee et al. [27] reported that of 135,701 procedures performed to treat carotid artery disease, 92% were performed for asymptomatic disease. If one can assume the low procedure risk of 2.3% stroke/death observed in ACAS, and the same risk of stroke in the medically treated patients, 115,730 unnecessary procedures were performed, and the cost to prevent one stroke in 5 years would be $369,685. Bunch and Kresowik [28] performed a US multicenter audit of CEA for asymptomatic disease and showed that the true risk of stroke and death from CEA in the USA was 3.8%; therefore, the cost of preventing one stroke or death over 5 years (in 2005 dollars) would be $428,510. This estimate is based upon the medical risk patients faced over 20 years ago. There are robust data demonstrating that the medical treatment of asymptomatic carotid disease has improved and that the risk of stroke for an asymptomatic carotid lesion has progressively diminished. Although there are no data reported for changes of medical care during ACAS, there are considerable data showing changes in medical care in ACST, which appear to have altered stroke risk for the asymptomatic carotid lesion during the study. At the initiation of ACST (1996), only 17% of patients were treated with statins. By the year 2000, 58% were on statins, and by 2008, 90% were

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on statins. The 5-year risk of ipsilateral stroke dropped from 5.3% in the first 5 years of ACST to 3.6% in years 6–10. It has been reported that diabetics treated with statins had a 46% relative risk reduction (RRR) of stroke [29], and patients with high cardiovascular risk had a 25% RRR of stroke if treated with a statin [30]. The SPARCL investigators [31] showed that in patients with stroke and TIAs randomized to statins, there was a 16% RRR of any stroke (p = 0.03) and a 35% risk reduction of a major cardiovascular event (p < 0.001). This study demonstrated that in the highest risk symptomatic patients, improved medical management reduces stroke. The more contemporary Oxford Vascular Study [32] and the SMART study [33] reported annualized risks of ipsilateral stroke from >50% asymptomatic carotid stenosis of 0.34% and 0.7%, respectively. Therefore, with current therapy, it will be difficult to justify operative intervention for most patients with asymptomatic carotid disease. Since most screening programs are designed to identify candidates with disease who would be considered for CEA or angioplasty and stenting, if the proposed intervention would no longer be considered appropriate, the screening program could not be justified.

Rationale of Stroke Prevention Screening The majority of strokes are ischemic strokes with sudden deprivation of blood flow to an area of the brain. ICA atherosclerosis, the leading cause of ischemic stroke, can cause a stroke by either reducing the blood flow to the brain or by embolizing atherosclerotic plaque or thrombus. Therefore, the best strategy seems to focus on prevention of stroke. In 1994, the National Stroke Association (NSA) recommended screening all persons over 50 years of age for carotid artery disease, atrial fibrillation, and hypertension. While this was an important statement, the recommended screening protocol included using a stethoscope to find cervical bruits for detection of carotid artery disease, palpating the pulse at the wrist to check for an irregular rhythm, and using a standard blood pressure reading for diagnosing hypertension [34].

Risk Factors for Stroke If risk factors for stroke can be defined, we can offer carotid screening only to those people who are at a higher risk of developing stroke. Review of the literature suggests the following factors to be associated with a higher risk for developing stroke: 1. Transient Ischemic Attack (TIA) TIAs are associated with substantially high risk of stroke and death. Johnson et al. followed 1,707 patients who

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3.

4.

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Role of Duplex Ultrasound in Carotid Screening

presented to emergency rooms with TIAs and found that 10% developed stroke within 90 days of their TIA and 5% died within 2 days. They identified any TIA persisting longer than 10 min to be a predictor of stroke [35]. Smoking The relative risk of stroke in heavy smokers (>40 cigarettes a day) is twice that of light smokers (70% ICA stenosis, the postoperative stroke rate was 15% if they underwent both CABG and CEA, while it was 0% if no CEA was done. This large study demonstrates that (1) the postoperative stroke rate for CABG patients is extremely low; and (2) in patients diagnosed preoperatively with a high-grade ICA stenosis, combined treatment (CABG plus CEA) is actually more harmful than not treating the ICA stenosis at all.

Role of Routine Carotid Duplex Screening in Patients with Lower Extremity Arterial Occlusive Disease The real question is whether a high-prevalence population can be reliably identified. Marek et al. [45] performed screening carotid duplex in 188 patients who presented with intermittent claudication and no cerebrovascular symptoms. Twenty percent were found to have a stenosis of 50–79%, 1.6% had stenosis of 80–99%, and 2.7% had evidence of carotid occlusion. The study concluded that the subset of patients aged >65 years, presence of carotid bruit, and ABI of 50% ICA stenosis (OR = 5.42). Turnipseed et al. [46] performed preoperative carotid duplex imaging in 330 patients who underwent coronary artery bypass (170) and peripheral vascular surgery (160). Patients with peripheral arterial disease had a higher incidence of carotid bruits compared to those with coronary artery disease (44% vs. 16%). In those patients who had a carotid bruit, there was 54% incidence of significant carotid artery disease. Patients with PAD had a 52% incidence of significant carotid disease compared with 11.7% of patients who underwent coronary artery bypass. This was not a true screening study as 43% of the patients with PAD had symptoms suggestive of cerebrovascular disease. Barnes et al. [47] prospectively screened 449 asymptomatic patients with carotid duplex before coronary or peripheral arterial reconstruction. They noted that the prevalence of carotid artery disease was significantly higher in patients who had PAD (28%) than in those patients who had coronary artery heart disease (15%). Additionally, patients who had asymptomatic carotid artery disease had an increased risk of neurologic events (15%) compared with patients without carotid artery disease (0.8%) during a 2-year follow-up.

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Moreover, there was an increased risk of perioperative and late death (10.6% and 9.2%, respectively) in patients who had asymptomatic carotid disease compared with patients who did not (0.3% and 0.8%, respectively, p < 0.001). Ahn et al. [48] reviewed the duplex scans of 78 patients who underwent carotid screening solely because of PAD and found that 14% had stenosis >50%, although they did not correlate the severity of the PAD to the presence of carotid stenoses. Their analysis showed that the risk factors of male sex, age > 68 years, hypertension, and previous cardiovascular surgery strongly correlated with carotid stenosis. They concluded that routine carotid duplex screening is indicated in older patients (age > 68 years) who have peripheral vascular disease. Fowl et al. [49] screened two patient groups in a Veterans Hospital setting for the presence of asymptomatic carotid stenosis. The first group had 152 patients without any history of PAD, and the second group consisted of 116 patients with PAD. Duplex screening revealed a 6.5% incidence of >50% carotid stenosis in the first group compared with 12% for the patients in the second group (p = 0.058). They recommended carotid surveillance in asymptomatic patients who have multiple atherosclerotic risk factors. Gentile et al. [50] reviewed retrospective data on 225 patients who underwent infrainguinal revascularization procedures with no previous carotid surgery and found that the presence of carotid bruit and the presence of rest pain were associated with >50% carotid stenosis. Among the subset of patients who had carotid bruit, 58% were found to have asymptomatic carotid stenosis of more than 50%. Virgilio et al. [51] prospectively screened patients with lower extremity atherosclerosis and found that 20% of asymptomatic male patients had a carotid stenosis of more than 50%. Hennerici et al. [52] screened 2,009 asymptomatic patients and divided them into three groups. The first group consisted of 375 patients who were examined before major vascular surgery (on aorta, iliac, or infrainguinal arteries), the second group had 264 patients with severe coronary artery disease, and the third group had 1,370 patients who had risk factors for atherosclerosis. The prevalence of asymptomatic carotid stenosis was 32.8% in the first group, 6.8% in the second group, and 5.9% in the third group (p < 0.001). These data suggest that patients undergoing major vascular surgery are at a much higher risk for harboring asymptomatic carotid artery stenosis as compared to those with coronary artery disease and those with risk factors for atherosclerosis.

Role of Ultrasound Follow-up for the Non-operated Carotid Artery After CEA The rationale behind postoperative carotid imaging is twofold. First, recurrent stenosis may be identified, and, second,

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disease progression in the non-operated ICA may be monitored regularly. Naylor et al. [53] followed 219 patients after carotid endarterectomy and specifically monitored their contralateral (non-operated, asymptomatic) ICA. 151 patients had regular duplex ultrasounds in the postoperative period. Cumulative freedom from stroke in the non-operated hemisphere was 99%, 96%, and 86% at 1, 5, and 10 years, respectively, giving a mean incidence of stroke of 1% per annum. Only one stroke was preceded by a transient ischemic event, and no stroke was associated with >70% stenosis of ICA. Ten patients (7%) with initially mild or moderate disease of the non-operated ICA progressed to severe stenosis during follow-up; only three became symptomatic and, in each case, the onset of symptoms preceded recognition of disease progression. The long-term risk of stroke in the non-operated ICA territory was small. The authors concluded that none of the observed strokes could have been prevented by postoperative surveillance following CEA. AbuRahma [54] performed a similar study evaluating arteries contralateral to a CEA in 534 patients. Serial duplex ultrasound was performed at 1 month postoperatively and thereafter every 6 months. Overall, carotid artery stenosis progressed in 36% of patients at mean follow-up of 41 months. Progression of stenosis was noted in 3% of patients with baseline normal carotid arteries. Carotid artery stenosis progressed in 36% of patients with less than 50% stenosis versus 47% of patients with 50–79% ICA stenosis. Late neurologic events referable to carotid artery stenosis were infrequent (6.7% in the entire series), including 2.4% strokes and 4.3% TIAs. Contralateral CEA was performed in 15% of patients. They concluded that duplex ultrasound should be performed every 6–12 months, if the stenosis is between 50% and 69%, and every 12–24 months if stenosis is less than 50%. Ballotta [55] followed asymptomatic contralateral ICAs of 599 patients who had undergone CEA for severe carotid disease. They performed duplex at 1 month and then every 6 months for a mean follow-up of 4.1 years. Disease progressed in 34% of patients with mild stenosis (30–49%) versus 47.9% of patients with moderate stenosis (50–69%). The median time to progression was 29.8 months for mild and 18.5 months for moderate stenosis. The rate of late neurologic events referable to contralateral ICA was 3.2% for the entire series and 4.8% for patients with a 30% of greater ICA stenosis. The study suggested duplex surveillance every 6 months in patients with >50% stenosis.

Cost-Effectiveness of Screening for Carotid Stenosis in Asymptomatic Patients Lee et al. [56] applied the cost-effectiveness analysis methods to the data from ACAS to determine cost-effectiveness of carotid screening. They assumed that the survival

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advantage offered by carotid endarterectomy for a 65-yearold man would last for 30 years, an assumption which is not justified according to insurance company life tables. The lifetime marginal cost-effectiveness of screening relative to no screening was $120,000 per quality-adjusted life year, which would double if life expectancy was targeted at a more realistic 15 years. Sensitivity analysis showed that marginal cost-effectiveness decreased to $50,000 or less per quality-adjusted life year only if a free screening instrument with perfect test characteristics was used in a population in which there was 40% prevalence of carotid stenosis. Therefore, a program to identify candidates for endarterectomy by screening asymptomatic populations for carotid stenosis costs more per quality-adjusted life year than is usually considered acceptable. Derdeyn et al. [57] developed a computer model to simulate the cost-effectiveness of screening a cohort of 1,000 men during a 20-year time period. Probabilities of stroke and death with surgical and medical management were obtained from published clinical trials. They showed that a one-time screening program of a population with a high prevalence (20%) of >60% stenosis costs $35,130 per incremental quality of life gained. Annual screening costs $457,773 per year of quality life gained. They concluded that the cost-effectiveness of a one-time screening program for an asymptomatic population with a high prevalence of carotid stenosis may be cost-effective, but annual screening is detrimental. Obuchowski et al. [58] constructed a model of the natural history of carotid artery disease using literature-based estimates of prevalence and incidence of carotid artery stenosis and associated morbidity and mortality. They found that carotid screening is effective only if rate of stenosis progression is >6% per year. However, if this rate is below 6%, screening is effective only if the prevalence rate in population is >20%, and if the rate of progression is below 1%, screening is effective only if the prevalence of disease in the population is more than 30%. Yin et al. [59] performed a cost-effectiveness analysis with a Markov model with data from ACAS and other trials. They found that for 60-year-old patients with a 5% prevalence of 60–99% asymptomatic stenosis, duplex ultrasound screening increased average quality-adjusted life years (QALY; 11.485 vs. 11.473) and lifetime cost of care ($5,500 vs. $5,012). Screening was cost-effective with the following conditions: disease prevalence was 4.5% or more, specificity of the duplex was 91% or more, stroke rate of patients who were medically treated was 3.3% or more, the relative risk reduction of surgery was 37% or more, the stroke rate associated with surgery was 160% or less than that of North American Symptomatic Carotid Endarterectomy Trial or ACAS perioperative complication rates, and the cost of ultrasound screening was $300 or less.

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According to ACAS data, 5-year absolute risk reduction for stroke for asymptomatic patients was 5.8%. Hill et al. [17] calculated that 17 patients in ACAS would require carotid endarterectomy to prevent one stroke (number needed to treat). Given the prevalence of disease in population, the resulting number of patients required to screen to prevent one stroke from ipsilateral asymptomatic carotid stenosis of ³80% would range from 850 to 1,700 (this figure may be as high as 8,500 if one considers the positive predictive value of duplex scanning used to demonstrate the prevalence of ACAS). The cost efficacy of such an approach would be difficult to justify.

Scoring System to Identify High-Risk Patients Qureshi et al. [60] developed and validated a simple scoring system based on routinely available information to identify persons at high risk for asymptomatic carotid artery stenosis using data collected during a community health screening program at various sites in western New York. They studied 1,331 volunteers without previous stroke, transient ischemic attack, or carotid artery surgery. Their evaluation included personal interviews and duplex ultrasound. The main outcome was carotid stenosis of more than 60% by duplex criteria. They identified four variables which were significantly associated with asymptomatic carotid artery stenosis of more than 60%: age > 65 years (odds ratio: 4.1), current smoking (odds ratio: 2), coronary artery disease (odds ratio: 2.4), and hypercholesterolemia (odds ratio: 1.9). They developed three risk groups (low, intermediate, and high) on the basis of total risk score assigned on the basis of strength association. The stratified scheme was validated. The posttest probability for the high-risk group was 35%, for those at intermediate risk 20%, and 7% for the low-risk group. Conclusions

Despite the increased interest related to patients with asymptomatic carotid artery stenosis, screening for carotid artery disease is difficult to justify. The prevalence of asymptomatic carotid artery stenosis in the general public and the risk of subsequent ipsilateral stroke are low. The number of patients needed to screen in order to prevent one stroke is excessive. Focused screening in patients at high risk due to peripheral vascular disease, coronary artery disease, or contralateral CEA improves yield; however, there are no data demonstrating that such an approach reduces stroke. At present, there are no data supporting screening for asymptomatic carotid disease in individuals appropriately treated for cardiovascular risk reduction. It is unlikely that screening for carotid artery disease will improve patient care or be cost-effective.

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