Cervical carotid artery stenosis latest

Cervical Carotid Artery Stenosis: Latest Update on Diagnosis and Management Peter Kan, MD, MPH, Maxim Mokin, MD, PhD, Travis M Dumont, MD, Kenneth V Snyder, MD, PhD, Adnan H Siddiqui, MD, PhD, Elad I Levy, MD, FACS, FAHA, and L Nelson Hopkins, MD Abstract: Carotid atherosclerotic disease is implicated in 15% to 30% of all ischemic strokes Carotid endarterectomy has been the standard treatment for carotid artery atherosclerosis, but carotid angioplasty and stenting have emerged as a less-invasive treatment alternative In this article, we review the recent literature on the epidemiology, pathophysiology, investigations, and treatment for atherosclerotic carotid artery disease, focusing on the role of carotid endarterectomy and carotid angioplasty and stenting in the treatment of symptomatic and asymptomatic carotid lesions (Curr Probl Cardiol 2012;37:127-169.) Drs Kan, Mokin, and Dumont have no conflicts of interest to disclose Dr Hopkins receives grant/research support from Toshiba; is a consultant for Abbott, Boston Scientific, Cordis, Micrus, W.L Gore; receives financial interest from AccessClosure, Augmenix, Boston Scientific, Claret Medical, Inc, Micrus, Valor Medical; sits as board/trustee/officer position for AccessClosure, Claret Medical, Inc; is on the speakers’ bureau for Abbott Vascular; and receives honoraria from Bard, Boston Scientific, Cordis, Memorial Healthcare System, Complete Conference Management, SCAI, and Cleveland Clinic Dr Levy receives research grant support (principal investigator: Stent-Assisted Recanalization in acute Ischemic Stroke, SARIS), other research support (devices), and honoraria from Boston Scientific, research support from Codman and Shurtleff, ev3/Covidien Vascular Therapies; holds ownership interests in Intratech Medical, Ltd and Mynx/Access Closure; is consultant for Codman and Shurtleff, ev3/Covidien Vascular Therapies, TheraSyn Sensors, Inc; and receives fees for carotid stent training from Abbott Vascular and ev3/Covidien Vascular Therapies He receives no consulting salary arrangements All consulting is per project and/or per hour Dr Siddiqui has received research grants from the National Institutes of Health (coinvestigator: NINDS 1R01NS064592-01A1, hemodynamic induction of pathologic remodeling leading to intracranial aneurysms), University at Buffalo; has financial interests in Hotspur, Intratech Medical, StimSox, Valor Medical; is consultant for Codman and Shurtleff, Concentric Medical, ev3/Covidien Vascular Therapies, GuidePoint Global Consulting, and Penumbra; serves on the speakers’ bureau for Codman and Shurtleff, Genentech; serves on the advisory board for Codman and Shurtleff; and receives honoraria from American Association of Neurological Surgeons’ courses, Emergency Medicine Conference, Genentech, Neocure Group; and also from Abbott Vascular and Codman and Shurtleff for training in carotid stenting and endovascular stenting for aneurysm He receives no consulting salary arrangements All consulting is per project and/or per hour Dr Snyder receives honoraria and an institutional grant from Toshiba Note: Boston Scientific’s neurovascular business has been acquired by Stryker Curr Probl Cardiol 2012;37:127-169 0146-2806/$ – see front matter doi:10.1016/j.cpcardiol.2011.11.001 Curr Probl Cardiol, April 2012 127 Prevalence of Carotid Artery Stenosis he prevalence of carotid artery stenosis varies with age, gender, and symptomatic status Each year, about 795,000 Americans suffer from a stroke, of which 80% are ischemic.1 Symptomatic carotid stenosis is implicated in 15% to 30% of all ischemic strokes.2,3 The reported prevalence of asymptomatic carotid artery stenosis of 50% or greater in patients less than 70 years of age is 4.8% for men and 2.2% for women.4 For patients 70 years or older, the prevalence rapidly increases to 12.5% and 6.9%, respectively In patients 80 years or older, the respective prevalence of severe asymptomatic carotid stenosis (defined as Ն70%) is 3.1% for men and 0.9% for women.4 T David R Holmes: Stroke is the most feared complication of cardiovascular disease as it is associated with major morbidity as well as mortality It is the third leading cause of death and disability and accounts for approximately $80 billion in health care costs Pathophysiology of Carotid Artery Stenosis and Potential for Targeted Therapy Atherosclerosis is a dualistic process whereby deposition of both soft and hard material occurs within an artery Atherosclerotic disease of the carotid artery has long been associated with typical concomitants of vascular disease, including hypercholesterolemia, hypertension, diabetes mellitus, obesity, and cigarette smoking.5,6 Its presence represents a potential source for stroke, and its treatment involves medical therapies to treat the aforementioned concomitant diseases More recently the role of systemic and local inflammation has been recognized as an important concomitant of atherosclerosis and thus a potential therapeutic target.7-11 Typical macroscopic plaque characteristics, such as ulceration and hemorrhage, may all be explained by a common pathway of inflammation Pathologic findings suggest inflammation plays a role in the development of atheromatous plaques and their transformation into symptomatic lesions.12 Carotid plaques removed from symptomatic patients frequently display signs of inflammation, including expression of inflammation mediators within the plaque.9,11,13,14 In addition, systemic markers of inflammation, such as elevated C-reactive protein, have been associated with an increased risk of carotid atherosclerosis progression and stroke.15 Microscopic evidence of inflammation within carotid atherosclerotic plaque may include expression of molecular inflammation 128 Curr Probl Cardiol, April 2012 mediators within plaque material, macrophage infiltration of plaque, evidence of hypoxia, and neovascularization This is particularly true in echolucent (or primary atheromatous) plaques rather than echogenic (primarily sclerotic) plaques.11 Such lesions are more likely to become symptomatic,16 possibly because of increased susceptibility to inflammatory changes, including neovascularization, hypoxia, necrosis, and thinning of the overlying fibrous cap.12 Subsequent inflammatory changes within an atheroma, such as necrosis and infiltration with macrophages, are strongly associated with cap rupture and time elapsed since ischemic events.14 The precise mechanism of why such inflammatory processes occur at the carotid bifurcation remains unclear However, it is likely that the development of carotid atherosclerosis is multifaceted As the association between inflammation and atherosclerosis becomes more evident, medical therapies targeted to halt or reverse inflammatory changes to carotid plaques are likely to emerge Aspirin, statins, and other medicines with anti-inflammatory properties that are already a part of the routine medical management of carotid artery stenosis may mitigate this effect.17 David R Holmes: The role of inflammation in cardiovascular disease, including cerebrovascular disease, has received increased attention The pleotrophic effect of statins is important in this regard Although this concept of the pathophysiologic significance of inflammation is the subject of intense interest, efforts to identify a specific etiologic agent, for example, a specific virus, have failed Pathology and Correlation with Neurologic Symptoms Degree of stenosis has been a mainstay in the design of randomized carotid trials to date Although relevant as a harbinger of stroke,18-20 degree of stenosis represents only measure of carotid plaque characterization Probably as important as the degree of stenosis is the rate of progression of stenosis For example, study showed that an increase from 50% to 69% to 90% to 99% in year or less is associated with a fourfold increased risk of ipsilateral stroke.21 In addition to degree of stenosis and rate of progression, potential markers of higher stroke risk in patients with carotid artery plaques include abnormal morphologic characteristics, such as ulceration, hemorrhage, and detection of cerebral microemboli or silent infarction These characteristics suggest a less stable atheromatous plaque that is more likely to embolize debris Not all Curr Probl Cardiol, April 2012 129 carotid plaques are alike, and identifying patients at greatest risk for ipsilateral ischemic events remains an important undertaking.21 David R Holmes: The underlying mechanisms of instability in carotid plaques, including plaque ulceration, hemorrhage, and embolization, bear similarities to many of those characteristics seen in acute coronary syndromes What is different, however, may be the finding that carotid stenosis severity is associated with increasingly worse acute outcomes, whereas in coronary circulation those lesions that result in subsequent acute myocardial infarction are often only moderate and less than 50% Plaque ulceration is among the most studied macroscopic irregularities noted in carotid artery stenosis Several studies have displayed a correlation between plaque irregularities and increased stroke risk.22-24 The reported prevalence of plaque ulceration on pathologic examination is highly variable in both asymptomatic (14%-82%) and symptomatic (36%-79%) patients but is consistently reported with greater frequency in symptomatic patients.23-26 Plaque ulceration has been correlated with microemboli detectable by transcranial Doppler ultrasonography,27 and its presence represents an increased risk for future stroke in symptomatic or asymptomatic patients Subgroup analysis from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) found a correlation between ulcerated plaque and 2-year stroke risk.22 The effect of plaque ulceration was seen in all degrees of stenosis, but ulceration was associated with increased relative risk (RR) of stroke in more stenotic vessels (from 1.24 in patients with 75% stenosis to 3.43 in patients with 95% stenosis) Intraplaque hemorrhage is most frequently seen in the context of plaque ulceration28 and represents another relevant marker for increased stroke incidence Microembolic activity, a risk factor for stroke,29 has been found in the setting of plaque hematoma.30,31 Like ulceration, on pathologic examination, intraplaque hemorrhage is seen more frequently in symptomatic patients (72%-94%) than asymptomatic patients (38%-71%).32,33 The natural history of carotid plaques is somewhat unclear, although the natural history of atherosclerotic disease is toward progression In a longitudinal study of patients randomized to medical treatment as part of the Asymptomatic Carotid Surgery Trial (ACST), several patients progressed to occlusion (with or without symptoms), whereas a minority of patients had diminished stenosis on follow-up imaging studies.21 Recent advancements in imaging studies may help identify plaques with con130 Curr Probl Cardiol, April 2012 cerning features, such as inflammation, hemorrhage, and ulceration, in addition to degree of stenosis, to predict impending ischemic events Diagnostic Investigations Carotid Ultrasonography Carotid ultrasonography is an excellent initial screening tool for the evaluation of patients with suspected carotid artery disease Its main advantage is its widespread availability and its noninvasive approach Color-flow analysis is used to visualize vessel lumen grossly and to identify the presence and direction of blood flow Traditionally, red shows blood flow toward the probe and blue indicates flow away from the probe Spectral Doppler analysis of waveforms is used for evaluation of arterial blood hemodynamic at specific areas of the vessel under investigation, providing indirect measurement of degree of stenosis Carotid ultrasonography also allows plaque composition analysis, which provides important information in assessing the risk of future stroke Heterogeneous plaques with hypoechoic lesions were shown to be an independent risk factor for ipsilateral stroke.34 In 2003, a multidisciplinary panel of experts from the Society of Radiologists in Ultrasound reviewed studies from multiple laboratories to develop recommendations for diagnosis and stratification of internal carotid artery (ICA) stenosis, which resulted in the publication of a consensus statement.35 The consensus of the panel was that peak systolic velocities of 125-230 cm/s correlated with 50% to 69% of ICA stenosis, and ICA stenosis of Ն70% was diagnosed when peak systolic velocities were greater than 230 cm/s Later, the consensus criteria for classifying carotid stenosis by ultrasound were validated and their initial accuracy was confirmed.36 Metaanalysis of the relationship between the degree of ICA by carotid ultrasound and digital subtraction angiography (DSA) also demonstrated excellent sensitivity and specificity of the ultrasound technique when diagnosing stenosis of 50% and above.37 However, carotid ultrasound is determined to be less accurate when measuring ICA stenosis below 50% As a result, the Society of Radiologists in Ultrasound does not recommend subcategories for minor degree of stenosis Certain special situations exist in which peak systolic velocities may not reflect accurately the severity of carotid artery stenosis For example, when the stenosis exceeds 90%, Doppler velocities often decrease and may be extremely low This is sometimes referred to as pseudonormalization Tandem lesions occur when or more areas of stenosis are found along the course of the ICA Tandem lesions can also present with falsely Curr Probl Cardiol, April 2012 131 diminished or normal range peak systolic velocities at the location of the more proximal stenosis This phenomenon is a result of diminished peak systolic velocities between the lesions Discordance between the degree of stenosis by gray-scale analysis and Doppler velocity measurements can help in identifying these lesions, and further evaluation with computed tomography (CT) or magnetic resonance (MR) angiography is recommended.38 Another scenario in which the measurements are altered falsely is the presence of severe contralateral ICA stenosis or occlusion Such a lesion will increase artificially the ipsilateral peak systolic velocities, and data from other imaging modalities should be considered when interpreting the degree of stenosis.39 Finally, gender differences between blood flow velocities through the ICA also exist, and women in general have higher carotid velocities than men.40 The main limitation of ultrasonography is that the technique is highly operator-dependent The measurements of blood flow velocities depend greatly on the degree of ultrasound beam angle, and both systolic and diastolic peak velocities increase with a greater angle.41 Failure to use a fixed insonation angle during diagnostic evaluation with carotid Doppler testing can result in errors Therefore, special attention is advised when performing measurements of tortuous vessels Suboptimal patient positioning, which is frequently encountered in patients who are intubated or have a high carotid bifurcation, can also limit significantly the diagnostic value of carotid ultrasound Despite these limitations, ultrasonography remains a widely used screening test for the evaluation of carotid artery disease because of its low cost and noninvasive nature The use of standardized technical parameters and methods when performing carotid ultrasound has improved the reliability of results As a general rule, when the results of carotid Doppler are unusual (such as unexpectedly low or high velocities, atypical waveforms, or suboptimal visualization), additional noninvasive imaging modalities or DSA should be performed to establish an accurate diagnosis Intravascular Ultrasound (IVUS) Successful application of intravascular sonography in the management of coronary atherosclerosis has led to its use in the evaluation and treatment of carotid artery disease In interventional cardiology, IVUS has been demonstrated to detect reliably early atherosclerotic disease and monitor further progression and regression of atherosclerotic lesions.42 When used for evaluation of the carotid arteries, IVUS helps to diagnose accurately intimal thickening, concentric plaque, and the presence of 132 Curr Probl Cardiol, April 2012 plaque ulceration and calcification, in addition to the degree of stenosis.43,44 Color-flow IVUS provides color-coded information regarding intraluminal blood flow to differentiate better atherosclerotic plaque lesions from the vessel lumen.45 When applied immediately after stenting and angioplasty, IVUS provides detailed information about stent apposition and in-stent thrombus, helping to establish whether further treatment is required In a series of 107 carotid angioplasty and stenting (CAS) procedures, Clark et al.46 reported that after a satisfactory result was demonstrated by angiography, subsequent IVUS findings resulted in additional treatment in 9% of patients: patients required poststent angioplasty, patients required additional stents to achieve complete plaque coverage, and patients were found to have stent malapposition Previous studies in which IVUS was applied show low complication risk, even when used before plaque dilatation.46,47 Nevertheless, the risk of vessel injury and difficulty in advancing the ultrasound probe in patients with tortuous vessels or through areas of high-grade stenosis limit the use of IVUS for routine assessment of carotid stenosis At our institution, it is reserved for clinical situations when noninvasive imaging or DSA alone fails to establish an accurate evaluation of carotid stenosis and for poststenting assessment (Fig 1) In interventional cardiology, IVUS has already demonstrated its cost-effectiveness during percutaneous coronary interventions.48 David R Holmes: The use of IVUS for routine assessment of carotid stenosis at the time of treatment may in part be related to a lack of familiarity with the device by some of the subspecialists involved in these procedures It also may be related to the absence of a large body of information on the advantages of procedural guidance in the carotids as compared to the coronary arterial tree CT Angiography CT angiography offers several advantages when evaluating for carotid artery disease, including noninvasive imaging and high spatial resolution This imaging modality has now become a standard test when evaluating patients with symptoms of stroke at many institutions The introduction of multidetector CT technology allows acquisition of multiple image slices simultaneously, which greatly improves the speed of imaging without loss of resolution.49 Metaanalysis of the diagnostic accuracy of CT angiography compared with DSA confirmed that CT angiography is accurate in detecting severe carotid stenosis and especially for detection of complete Curr Probl Cardiol, April 2012 133 Fig IVUS after CAS shows good wall apposition and no in-stent thrombus occlusion, where its sensitivity and specificity reach 97% and 99%.50 In clinical practice, CT angiography is often performed following carotid ultrasound imaging that shows positive results for carotid artery disease In a recent study assessing the cost-effectiveness of various noninvasive imaging modalities, Tholen et al.51 demonstrated that immediate CT angiography is indicated for patients with a high-risk profile for stroke or with a high prior probability of carotid artery stenosis or who can undergo surgery within weeks after the initial symptoms of transient ischemic attack (TIA) or minor stroke In addition to providing accurate measurements of luminal narrowing, CT angiography reliably assesses the characteristics of carotid artery atherosclerotic plaques Although histologic plaque composition is better evaluated with MR angiography technique, CT angiography shows excellent sensitivity for detection of carotid plaque calcifications (Fig 2) Nevertheless, it should be noted that in the presence of extensive dense calcifications, beam-hardening artifact can obscure visualization of the carotid artery lumen and provide inaccurate estimation of the degree of stenosis CT angiography is also capable of detecting large lipid-rich 134 Curr Probl Cardiol, April 2012 Fig CT angiography of the ICA, coronal view (left) and 3D reconstruction (right), in a patient with suspected bilateral carotid artery stenosis shows extensive plaque calcifications at both carotid bifurcations and severe stenosis at both ICA origins necrotic core lesions and plaque hemorrhages; however, its diagnostic accuracy in detecting smaller lesions is less reliable.52 Because CT angiography is associated with radiation use, the imaging protocol setting should be closely observed to limit radiation exposure CT angiography involves administration of intravenous contrast material, which has the potential for contrast-induced renal failure, especially in patients with preexisting renal disease Baseline renal function tests, including glomerular filtration rate, help to determine whether the administration of nephroprotective agents, such as bicarbonate and acetylcysteine, is necessary to minimize the risk of renal injury David R Holmes: The authors comment on the potential strategies to minimize the risk of renal injury The efficacy of these approaches to minimize this, however, has been found to be disappointing when evaluated in rigorous large-scale randomized trials Curr Probl Cardiol, April 2012 135 Fig Asymmetrical CT perfusion maps in a patient with high-grade left ICA stenosis before carotid artery stenting demonstrate increased CBV (top middle), TTP (top right), and MTT (bottom middle) in the left hemisphere, indicating maximized autoregulatory hemodynamic mechanisms to preserve brain perfusion Such changes suggest that this patient is at higher risk to develop hyperperfusion syndrome CT Perfusion A combination of CT angiography with CT perfusion enables analysis of hemodynamic parameters associated with carotid artery disease Whole-brain CT perfusion imaging with 320-detector-row CT scanners allows examination of the entire brain, providing valuable information about regions of the brain that are at risk for ischemia and status of the collateral circulation Modern CT perfusion parameters include cerebral blood volume (CBV), cerebral blood flow (CBF), time-to-peak (TTP), and mean transient time (MTT) Symmetrical perfusion maps between the hemispheres indicate normal cerebral circulation, whereas asymmetry in the vascular territory corresponding to the affected ICA may serve as a measure of perfusion disturbance (Fig 3) Changes in MTT and CBV can be observed in patients with ICA stenosis above 50%.53 These changes are thought to represent autoregulatory vasodilation—a compensatory mechanism that is intended to preserve cerebral oxygenation when collateral circulation alone is not adequate to maintain physiological parameters of cerebral blood perfu136 Curr Probl Cardiol, April 2012 Comparison of Embolic Protection Devices In 2009, Garg et al.123 published a metaanalysis comparing outcomes in protected and unprotected CAS On the basis of the 134 articles published between 1995 and 2007 that were included in their final analysis, the authors found significant benefit for using protection devices during CAS in both symptomatic patients (RR 0.67; 95% confidence interval 0.520.56) and asymptomatic patients (RR 0.61; 95% confidence interval 0.41-0.90) The overall risk of stroke was estimated to be reduced by 38% Studies using distal ICA occlusion balloons, filters, and proximal occlusion devices were included in this metaanalysis Interestingly, the authors also found that protection devices started to show significant benefit in preventing embolic events beginning in 2004, indicating that more recently developed devices are superior to earlier models The most recent guidelines on the management of patients with extracranial carotid artery disease recommend the use of embolic protection devices during CAS to reduce the risk of periprocedural stroke.69 High-Risk Patients for CAS We are just beginning to understand the high-risk factor for CAS (unlike for CEA) We now know that several anatomic, patient, and lesion characteristics increase the risk of CAS: these include difficult aortic arch (Type or arch, bovine arch), diseased aortic arch, occluded or diseased external carotid artery, significant carotid tortuosity, absence of a distal landing zone, concentric calcification, hemorrhagic plaque, carotid origin disease, and severe peripheral vascular disease with difficult access In patients with or more of these characteristics, CEA should be considered as an alternative treatment, especially when none of the above high-risk factors for CAS is considered high risk for CEA Cerebral Hyperperfusion Syndrome Cerebral hyperperfusion syndrome is a rare complication associated with ICA revascularization, described following both CEA and stenting.124 Severity of ICA stenosis is an independent factor for development of hyperperfusion syndrome This syndrome usually occurs within the first few days following intervention and is believed to be secondary to impaired autoregulation mechanisms However, delayed presentations several weeks after surgery have also been described Clinical presentation can be variable and includes headaches, seizures, and focal neurological deficits The extreme manifestation of cerebral hyperperfusion syndrome is intracerebral hemorrhage, which is associated with high mortality rates Close monitoring of blood pressure parameters following Curr Probl Cardiol, April 2012 155 Fig Because of a change in neurologic status 12 hours after left carotid artery stenting (case from Fig 5), a follow-up noncontrast CT scan was obtained and reveals a focal hemorrhage in the posterior limb of the internal capsule, because of hyperperfusion syndrome revascularization procedures is of critical importance to prevent development of hemorrhage Several studies have assessed the role of CT perfusion in predicting development of cerebral hyperperfusion syndrome (Figs and 6) At present, there is no agreement on which perfusion sequence can identify most reliably patients who are at higher risk for cerebral hyperperfusion syndrome Data suggest that MTT or TTP and CBV can serve as potential diagnostic tools when screening for patients who are at higher risk (patients with increased MTT or TTP and CBV) to develop this complication.125,126 Management of Asymptomatic Carotid Stenosis The best evidence concerning the treatment of asymptomatic carotid stenosis comprised trials, the ACAS110 and the ACST.127 To date, only 156 Curr Probl Cardiol, April 2012 small trial (consisting of 85 patients) has compared endarterectomy directly with stenting for patients with asymptomatic disease, with similar results between the treatments.128 The SAPPHIRE trial97 and CREST102,129 included symptomatic and asymptomatic patients Both trials suggested that CAS was comparable to endarterectomy for perioperative morbidity Trials underway may offer a new perspective on the treatment of asymptomatic carotid disease SPACE-2 is a large randomized trial that is currently randomizing patients to endarterectomy, stenting, or best medical management.130 The Case for Carotid Endarterectomy vs Best Medical Management The ACAS randomized 1662 patients with asymptomatic carotid stenosis to CEA plus best medical treatment or best medical treatment alone.110 Three patients were lost to follow-up after randomization to endarterectomy; the remaining 1559 patients were included in the analysis Inclusion criteria included carotid stenosis of at least 60% measured by DSA or Doppler ultrasonography Entry criteria included age between 40 and 79 years and no previous cerebrovascular infarction in the study vessel Patients were enrolled between 1987 and 1993 Best medical treatment during enrollment consisted of antiplatelet therapy with 325 mg of aspirin and antihypertensive treatment The primary endpoint was cerebral infarction occurring in the region of the study artery or any stroke or death, measured as 5-year aggregate risk as a percentage With respect to the primary endpoint, the trial was favorable to CEA, with a 5-year risk of stroke or death of 5.1% for patients undergoing surgery compared with 11.0% for patients randomized to medical treatment There were 146 patients who crossed over from treatment arm to the other for a variety of reasons More than two-thirds of these patients were randomized to endarterectomy In total, 12% of patients randomized to endarterectomy did not undergo surgery, and 5% of patients randomized to medical management underwent ipsilateral endarterectomy An astreated analysis showed no significant change in the primary outcome, with a 5-year risk of stroke or death of 5.1% for patients undergoing surgery compared with 11.5% for patients treated with medical management The ACST randomized 3120 patients with asymptomatic carotid stenosis to CEA plus best medical management or best medical management alone.127 Carotid stenosis for all patients was measured at 60% or greater by Doppler ultrasonography Entry criteria included no previous cerebrovascular infarction ipsilateral to the study vessel Surgical intervention Curr Probl Cardiol, April 2012 157 was to be performed as soon as possible after randomization, with specifics of anesthesia and shunting to be determined by the operating surgeons Patients were enrolled between 1993 and 2003, during which time medical management included antiplatelet therapy, antihypertensive treatment, and lipid-lowering therapy The primary endpoint comprised perioperative morbidity and nonperioperative stroke Perioperative morbidity included stroke, MI, and death and was measured at 3.5% for all patients undergoing surgery, including crossover patients The primary endpoint was reported as 5-year stroke (including contralateral stroke) or death risk With respect to the primary endpoint, the trial was favorable toward stroke-preventing CEA, as patients randomized to surgery had a 6.4% 5-year risk of stroke or death compared with 11.7% for patients randomized to medical treatment There was significant crossover in both groups, with 9% of patients randomized to surgery having never undergone endarterectomy, and 18% of patients randomized to medical surgery undergoing ipsilateral endarterectomy by the fifth year of follow-up Medical treatment with antiplatelet and antihypertensive therapies was consistent with approximately 90% of patients in the study receiving antiplatelet therapy and approximately 81% receiving hypertensive therapy However, the use of lipid-lowering therapy was noted to increase throughout the trial from 17% of those randomized in the earliest years of the study to an estimated 70% of all surviving patients at completion of the study Comparison of Carotid Angioplasty and Stenting vs Carotid Endarterectomy To date, no large randomized trial has compared directly the safety of CAS to endarterectomy in asymptomatic patients Two trials, SAPPHIRE and CREST, have randomized both symptomatic and asymptomatic patients The best evidence comparing stenting and endarterectomy in such patients can be elicited from subgroup analysis of these trials The SAPPHIRE trial97 randomized 334 patients before early termination Of these, 238 patients had asymptomatic disease The primary endpoint was incidence of stroke, MI, or death within 30 days of intervention The incidence of the primary endpoint was nearly double for patients undergoing endarterectomy (10.2%) compared to patients undergoing stenting (5.4%), although the result was not statistically significant (P ϭ 0.20) In CREST, 1180 of 2502 patients randomized had asymptomatic carotid stenosis.102,129 There was no statistically significant difference in the primary outcome between asymptomatic patients randomized to endar158 Curr Probl Cardiol, April 2012 terectomy (3.6%) or stenting (3.5%) The periprocedural morbidity was similar to that reported for patients undergoing endarterectomy in the ACST trial (3.5%) The Asymptomatic Carotid stenosis, stenting vs endarterectomy Trial (ACT-1)112 aims to test definitively the equivalence of CAS to endarterectomy in asymptomatic patients with severe carotid stenosis This trial is planned to enroll 1600 patients with a target study completion date of 2017 Patients with severe carotid stenosis are randomized at a 3:1 ratio to either CAS or CEA Stenting procedures (XACT; Abbott) are performed with mandatory distal protection (NAV 6; Abbott) The primary outcome is an occurrence of major adverse events within the 30 days following intervention The target date for data collection of this measure is August 2012 The 5-year incidence of ipsilateral stroke or death will be compared on study completion Improvements in Medical Management and a Definitive Three-Arm Trial Improvements of medical management with antihyperlipidemic and antihypertensive agents unavailable during the design of ACAS and ACST have brought into question whether carotid artery revascularization procedures are indicated for asymptomatic patients.130-132 The reported annual risk of ipsilateral stroke in patients with asymptomatic carotid stenosis of 60% or greater has decreased since the publication of ACAS (11.0% over years, or approximately 2.2% yearly) to roughly 1% per year in a study of 200 patients undergoing evaluation with ultrasonic embolic detection published in 2005.133 Of interest, 9.1% of patients randomized to the medical arm of ACST had an ipsilateral ischemic stroke.21 The yearly stroke risk was approximately 1.7% Recent prospective studies of patients with 50% or more carotid stenosis have shown very low incidence of ipsilateral stroke, with rates between 0.34%134 and 0.8%.135 Thus, with a diminished annual risk of stroke in the asymptomatic patient, the results of ACAS and ACST seem dated, the results for asymptomatic patients in SAPPHIRE and CREST seem irrelevant, and those for ACT-1 seem potentially irrelevant The best evidence concerning the treatment of asymptomatic carotid stenosis may be on the horizon with an ongoing trial SPACE-2 has a targeted completion date of 2015.130 This trial is planned to enroll 3640 patients with asymptomatic carotid artery stenosis to of arms Patients with carotid stenosis of 70% or more by Doppler ultrasonography are eligible All patients will be treated with best medical management (antiplatelet and antihyperlipiCurr Probl Cardiol, April 2012 159 demic) and individual risk-factor modification Patients will be randomized at a rate of 3:3:1 to endarterectomy, stenting, or medical management without intervention Endarterectomy and stenting interventionists must have performed at least 40 procedures in the previous 24 months, with 20 procedures completed within the first SPACE trial with a complication rate of 6% or less The primary endpoint is the 5-year risk of ipsilateral stroke or death In addition, 30-day postoperative risk of stroke, death, and MI will be compared between patients undergoing endarterectomy or stenting Conclusions CEA and CAS are complementary procedures for the treatment of atherosclerotic carotid disease Much has been learned about them from RCTs and clinical experience Given the lack of embolic protection device use and operator inexperience that characterize most European trials, CREST represents the largest, most rigorous and complete examination of CAS vs CEA to date, including both symptomatic and asymptomatic standard-risk patients The results of CREST establish both CAS and CEA as very safe and effective choices for patients and their physicians Ultimately, patient preference will have to be considered in the decision-making process, and outcomes can be optimized by choosing the right procedure for the right patient David R Holmes: Given the very large burden of mortality and morbidity associated with stroke, there has been intense interest in carotid arterial stenosis This field continues to evolve with new insights into the pathophysiology of the disease and refinements in diagnostic and therapeutic regimens This current article features an in-depth discussion about the changing field of treatments with new approaches, such as proximal embolic protection during carotid arterial stenting After an in-depth discussion of the different options, medical, surgical, and interventional, the authors rightly conclude that ultimately patient preference will have to be considered in the decisionmaking process, and outcomes can be optimized by choosing the right procedure for the right patient Acknowledgments: The authors thank Paul H Dressel, BFA, for preparation of the illustrations and Debra J Zimmer, AAS, CMA, for editorial assistance REFERENCES Roger VL, Go AS, Lloyd-Jones DM, et al Heart Disease and Stroke Statistics— 2011 Update: A Report from the American Heart Association Circulation 2011; 123:e18-e209 160 Curr Probl Cardiol, April 2012 Henry M, Polydorou A, Klonaris C, et al Carotid angioplasty and stenting under protection State of the art Minerva Cardioangiol 2007;55:19-56 Kolominsky-Rabas PL, Weber M, Gefeller O, et al Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study Stroke 2001; 32:2735-40 de Weerd M, Greving JP, Hedblad B, et al Prevalence of asymptomatic carotid artery stenosis in the general population: an individual participant data metaanalysis Stroke 2010;41:1294-7 Bogousslavsky J, Regli F, Van Melle G Risk factors and concomitants of internal carotid artery occlusion or stenosis A controlled study of 159 cases Arch Neurol 1985;42:864-7 Duncan GW, Lees RS, Ojemann RG, et al Concomitants of atherosclerotic carotid artery stenosis Stroke 1977;8:665-9 Hermus L, Lefrandt JD, Tio RA, et al Carotid plaque formation and serum biomarkers Atherosclerosis 2010;213:21-9 Klingenberg R, Hansson GK Treating inflammation in atherosclerotic cardiovascular disease: emerging therapies Eur Heart J 2009;30:2838-44 Krupinski J, Font A, Luque A, et al Angiogenesis and inflammation in carotid atherosclerosis Front Biosci 2008;13:6472-82 10 Ridker PM, Silvertown JD Inflammation, C-reactive protein, and atherothrombosis J Periodontol 2008;79:1544-51 11 Sirico G, Spadera L, De Laurentis M, et al Carotid artery disease and stroke in patients with peripheral arterial disease The role of inflammation Monaldi Arch Chest Dis 2009;72:10-7 12 Stoll G, Bendszus M Inflammation and atherosclerosis: novel insights into plaque formation and destabilization Stroke 2006;37:1923-32 13 DeGraba TJ Expression of inflammatory mediators and adhesion molecules in human atherosclerotic plaque Neurology 1997;49:S15-9 14 Redgrave JN, Lovett JK, Gallagher PJ, et al Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study Circulation 2006;113:2320-8 15 Ridker PM, Cushman M, Stampfer MJ, et al Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men N Engl J Med 1997;336:973-9 16 Golledge J, Cuming R, Ellis M, et al Carotid plaque characteristics and presenting symptom Br J Surg 1997;84:1697-701 17 Crisby M, Nordin-Fredriksson G, Shah PK, et al Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization Circulation 2001;103:926-33 18 Dempsey RJ, Diana AL, Moore RW Thickness of carotid artery atherosclerotic plaque and ischemic risk Neurosurgery 1990;27:343-8 19 Rothwell PM, Gibson R, Warlow CP Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis On behalf of the European Carotid Surgery Trialists’ Collaborative Group Stroke 2000;31: 615-21 Curr Probl Cardiol, April 2012 161 20 Rothwell PM, Salinas R, Ferrando LA, et al Does the angiographic appearance of a carotid stenosis predict the risk of stroke independently of the degree of stenosis? Clin Radiol 1995;50:830-3 21 Hirt LS Progression rate and ipsilateral neurological events in asymptomatic carotid stenosis Stroke [epub ahead of print 2011] 22 Eliasziw M, Streifler JY, Fox AJ, et al Significance of plaque ulceration in symptomatic patients with high-grade carotid stenosis North American Symptomatic Carotid Endarterectomy Trial Stroke 1994;25:304-8 23 Park AE, McCarthy WJ, Pearce WH, et al Carotid plaque morphology correlates with presenting symptomatology J Vasc Surg 1998;27:872-9 24 Troyer A, Saloner D, Pan XM, et al Major carotid plaque surface irregularities correlate with neurologic symptoms J Vasc Surg 2002;35:741-7 25 Ballotta E, Da Giau G, Renon L Carotid plaque gross morphology and clinical presentation: a prospective study of 457 carotid artery specimens J Surg Res 2000;89:78-84 26 Fisher M, Paganini-Hill A, Martin A, et al Carotid plaque pathology: thrombosis, ulceration, and stroke pathogenesis Stroke 2005;36:253-7 27 Sitzer M, Müller W, Siebler M, et al Plaque ulceration and lumen thrombus are the main sources of cerebral microemboli in high-grade internal carotid artery stenosis Stroke 1995;26:1231-3 28 U-King-Im JM, Fox AJ, Aviv RI, et al Characterization of carotid plaque hemorrhage: a CT angiography and MR intraplaque hemorrhage study Stroke 2010;41:1623-9 29 Spagnoli LG, Mauriello A, Sangiorgi G, et al Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke JAMA 2004;292:1845-52 30 Altaf N, Daniels L, Morgan PS, et al Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events J Vasc Surg 2008;47:337-42 31 Altaf N, Goode SD, Beech A, et al Plaque hemorrhage is a marker of thromboembolic activity in patients with symptomatic carotid disease Radiology 2011;258:538-45 32 Ansel GM, Hopkins LN, Jaff MR, et al Safety and effectiveness of the INVATEC MO MA proximal cerebral protection device during carotid artery stenting: results from the ARMOUR pivotal trial Catheter Cardiovasc Interv 2010;76:1-8 33 Montauban van Swijndregt AD, Elbers HR, Moll FL, et al Cerebral ischemic disease and morphometric analyses of carotid plaques Ann Vasc Surg 1999; 13:468-74 34 Polak JF, Shemanski L, O’Leary DH, et al Hypoechoic plaque at US of the carotid artery: an independent risk factor for incident stroke in adults aged 65 years or older Cardiovascular Health Study Radiology 1998;208:649-54 35 Grant EG, Benson CB, Moneta GL, et al Carotid artery stenosis: grayscale and Doppler ultrasound diagnosis—Society of Radiologists in Ultrasound consensus Conference Ultrasound Q 2003;19:190-8 36 Braun RM, Bertino RE, Milbrandt J, et al Ultrasound imaging of carotid artery stenosis: application of the Society of Radiologists in ultrasound Consensus Criteria to a Single Institution Clinical Practice Ultrasound Q 2008;24:161-6 162 Curr Probl Cardiol, April 2012 37 Jahromi AS, Cinà CS, Liu Y, et al Sensitivity and specificity of color duplex ultrasound measurement in the estimation of internal carotid artery stenosis: a systematic review and meta-analysis J Vasc Surg 2005;41:962-72 38 Romero JM, Lev MH, Chan ST, et al US of neurovascular occlusive disease: interpretive pearls and pitfalls RadioGraphics 2002;22:1165-76 39 Henderson RD, Steinman DA, Eliasziw M, et al Effect of contralateral carotid artery stenosis on carotid ultrasound velocity measurements Stroke 2000;31:2636-40 40 Comerota AJ, Salles-Cunha SX, Daoud Y, et al Gender differences in blood velocities across carotid stenoses J Vasc Surg 2004;40:939-44 41 Tola M, Yurdakul M Effect of Doppler angle in diagnosis of internal carotid artery stenosis J Ultrasound Med 2006;25:1187-92 42 Kaneda H, Ako J, Terashima M Intravascular ultrasound imaging for assessing regression and progression in coronary artery disease Am J Cardiol 2010;106:1735-46 43 Manninen HI, Räsänen H, Vanninen RL, et al Human carotid arteries: correlation of intravascular US with angiographic and histopathologic findings Radiology 1998;206:65-74 44 Miskolczi L, Guterman LR, Flaherty JD, et al Depiction of carotid plaque ulceration and other plaque-related disorders by intravascular sonography: a flow chamber study AJNR Am J Neuroradiol 1996;17:1881-90 45 Irshad K, Reid DB, Miller PH, et al Early clinical experience with color three-dimensional intravascular ultrasound in peripheral interventions J Endovasc Ther 2001;8:329-38 46 Clark DJ, Lessio S, O’Donoghue M, et al Safety and utility of intravascular ultrasound-guided carotid artery stenting Catheter Cardiovasc Interv 2004;63:355-62 47 Zacharatos H, Hassan AE, Qureshi AI Intravascular ultrasound: principles and cerebrovascular applications AJNR Am J Neuroradiol 2010;31:586-97 48 Mueller C, Hodgson JM, Schindler C, et al Cost-effectiveness of intracoronary ultrasound for percutaneous coronary interventions Am J Cardiol 2003;91:143-7 49 Kim JJ, Dillon WP, Glastonbury CM, et al Sixty-four-section multidetector CT angiography of carotid arteries: a systematic analysis of image quality and artifacts AJNR Am J Neuroradiol 2010;31:91-9 50 Koelemay MJ, Nederkoorn PJ, Reitsma JB, et al Systematic review of computed tomographic angiography for assessment of carotid artery disease Stroke 2004;35:2306-12 51 Tholen AT, de Monyé C, Genders TS, et al Suspected carotid artery stenosis: cost-effectiveness of CT angiography in work-up of patients with recent TIA or minor ischemic stroke Radiology 2010;256:585-97 52 Wintermark M, Jawadi SS, Rapp JH, et al High-resolution CT imaging of carotid artery atherosclerotic plaques AJNR Am J Neuroradiol 2008;29:875-82 53 Jongen LM, van der Worp HB, Waaijer A, et al Interrelation between the degree of carotid stenosis, collateral circulation and cerebral perfusion Cerebrovasc Dis 2010;30:277-84 54 Chen A, Shyr MH, Chen TY, et al Dynamic CT perfusion imaging with acetazolamide challenge for evaluation of patients with unilateral cerebrovascular steno-occlusive disease AJNR Am J Neuroradiol 2006;27:1876-81 55 Gaudiello F, Colangelo V, Bolacchi F, et al Sixty-four-section CT cerebral perfusion evaluation in patients with carotid artery stenosis before and after stenting with a cerebral protection device AJNR Am J Neuroradiol 2008;29:919-23 Curr Probl Cardiol, April 2012 163 56 Buskens E, Nederkoorn PJ, Buijs-Van Der Woude T, et al Imaging of carotid arteries in symptomatic patients: cost-effectiveness of diagnostic strategies Radiology 2004;233:101-12 57 Townsend TC, Saloner D, Pan XM, et al Contrast material-enhanced MRA overestimates severity of carotid stenosis, compared with 3D time-of-flight MRA J Vasc Surg 2003;38:36-40 58 Nederkoorn PJ, van der Graaf Y, Hunink MG Duplex ultrasound and magnetic resonance angiography compared with digital subtraction angiography in carotid artery stenosis: a systematic review Stroke 2003;34:1324-32 59 Lell M, Fellner C, Baum U, et al Evaluation of carotid artery stenosis with multisection CT and MR imaging: influence of imaging modality and postprocessing AJNR Am J Neuroradiol 2007;28:104-10 60 Takaya N, Yuan C, Chu B, et al Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI—initial results Stroke 2006;37:818-23 61 Takaya N, Yuan C, Chu B, et al Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study Circulation 2005;111:2768-75 62 Kooi ME, Cappendijk VC, Cleutjens KB, et al Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging Circulation 2003;107:2453-8 63 Corti R, Fuster V, Fayad ZA, et al Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years’ follow-up by highresolution noninvasive magnetic resonance imaging Circulation 2002;106:2884-7 64 Tang TY, Howarth SP, Miller SR, et al The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease J Am Coll Cardiol 2009;53:2039-50 65 Al-Ameri H, Thomas ML, Yoon A, et al Complication rate of diagnostic carotid angiography performed by interventional cardiologists Catheter Cardiovasc Interv 2009;73:661-5 66 Leonardi M, Cenni P, Simonetti L, et al Retrospective study of complications arising during cerebral and spinal diagnostic angiography from 1998 to 2003 Interv Neuroradiol 2005;11:213-21 67 Schneider PA, Silva MB Jr, Bohannon WT, et al Safety and efficacy of carotid arteriography in vascular surgery practice J Vasc Surg 2005;41:238-45 68 Connors JJ, 3rd, Sacks D, Furlan AJ, et al Training, competency, and credentialing standards for diagnostic cervicocerebral angiography, carotid stenting, and cerebrovascular intervention: a joint statement from the American Academy of Neurology, the American Association of Neurological Surgeons, the American Society of Interventional and Therapeutic Neuroradiology, the American Society of Neuroradiology, the Congress of Neurological Surgeons, the AANS/CNS Cerebrovascular Section, and the Society of Interventional Radiology J Vasc Interv Radiol 2009;20:S292-301 69 Brott TG, Halperin JL, Abbara S, et al ASA/ACCF/AHA/AANN/AANS/ACR/ ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease A report of the American College of Cardiology Foundation/American Heart Association Task 164 Curr Probl Cardiol, April 2012 70 71 72 73 74 75 76 77 78 79 80 81 82 83 Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery Circulation 2011; 124:e54-130 Kawamoto R, Oka Y, Tomita H, et al Non-HDL cholesterol as a predictor of carotid atherosclerosis in the elderly J Atheroscler Thromb 2005;12:143-8 Makris GC, Lavida A, Nicolaides AN, et al The effect of statins on carotid plaque morphology: a LDL-associated action or one more pleiotropic effect of statins? Atherosclerosis 2010;213:8-20 Amarenco P, Bogousslavsky J, Callahan A 3rd, et al High-dose atorvastatin after stroke or transient ischemic attack N Engl J Med 2006;355:549-59 Sillesen H, Amarenco P, Hennerici MG, et al Atorvastatin reduces the risk of cardiovascular events in patients with carotid atherosclerosis: a secondary analysis of the Stroke Prevention by Aggressive Reduction in cholesterol Levels (SPARCL) trial Stroke 2008;39:3297-302 CAPRIE Steering Committee A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) Lancet 1996;348:1329-39 Bhatt DL, Fox KA, Hacke W, et al Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events N Engl J Med 2006;354:1706-17 Diener HC, Bogousslavsky J, Brass LM, et al Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial Lancet 2004;364:331-7 Adams RJ, Albers G, Alberts MJ, et al Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack Stroke 2008;39:1647-52 Dalainas I, Nano G, Bianchi P, et al Dual antiplatelet regime versus acetyl-acetic acid for carotid artery stenting Cardiovasc Interv Radiol 2006;29:519-21 McKevitt FM, Randall MS, Cleveland TJ, et al The benefits of combined anti-platelet treatment in carotid artery stenting Eur J Vasc Endovasc Surg 2005;29:522-7 Grewe PH, Deneke T, Machraoui A, et al Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen J Am Coll Cardiol 2000;35:157-63 Kim H, Lee HK, Han K, et al Prevalence and risk factors for aspirin and clopidogrel resistance in patients with coronary artery disease or ischemic cerebrovascular disease Ann Clin Lab Sci 2009;39:289-94 Prabhakaran S, Wells KR, Lee VH, et al Prevalence and risk factors for aspirin and clopidogrel resistance in cerebrovascular stenting AJNR Am J Neuroradiol 2008;29:281-5 Eastcott HHG, Pickering GW, Rob CG Reconstruction of internal carotid artery in a patient with intermittent attacks of hemiplegia Lancet 1954;2:994-6 Curr Probl Cardiol, April 2012 165 84 Fields WS, Maslenikov V, Meyer JS, et al Joint study of extracranial arterial occlusion V Progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions JAMA 1970;211:1993-2003 85 Shaw DA, Venables GS, Cartlidge NE, et al Carotid endarterectomy in patients with transient cerebral ischaemia J Neurol Sci 1984;64:45-53 86 North American Symptomatic Carotid Endarterectomy Trial Collaborators Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis N Engl J Med 1991;325:445-53 87 Paciaroni M, Eliasziw M, Kappelle LJ, et al Medical complications associated with carotid endarterectomy North American Symptomatic Carotid Endarterectomy Trial (NASCET) Stroke 1999;30:1759-63 88 Barnett HJ, Taylor DW, Eliasziw M, et al Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis North American Symptomatic Carotid Endarterectomy Trial Collaborators N Engl J Med 1998;339:1415-25 89 European Carotid Surgery Trialists’ Collaborative Group MRC, European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis Lancet 1991;337:1235-43 90 European Carotid Surgery Trialists’ Collaborative Group Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC, European Carotid Surgery Trial (ECST) Lancet 1998;351:1379-87 91 Mayberg MR, Wilson SE, Yatsu F, et al Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis Veterans Affairs Cooperative Studies Program 309 Trialist Group JAMA 1991;266:3289-94 92 Rothwell PM, Eliasziw M, Gutnikov SA, et al Analysis of pooled data from the randomised controlled trials of endarterectomy for symptomatic carotid stenosis Lancet 2003;361:107-16 93 Gasecki AP, Eliasziw M, Ferguson GG, et al Long-term prognosis and effect of endarterectomy in patients with symptomatic severe carotid stenosis and contralateral carotid stenosis or occlusion: results from NASCET North American Symptomatic Carotid Endarterectomy Trial (NASCET) Group J Neurosurg 1995;83:778-82 94 Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery transluminal angioplasty Study (CAVATAS): a randomised trial Lancet 2001;357:1729-37 95 Diethrich EB, Ndiaye M, Reid DB Stenting in the carotid artery: initial experience in 110 patients J Endovasc Surg 1996;3:42-62 96 Yadav JS, Roubin GS, Iyer S, et al Elective stenting of the extracranial carotid arteries Circulation 1997;95:376-81 97 Yadav JS, Wholey MH, Kuntz RE, et al Protected carotid-artery stenting versus endarterectomy in high-risk patients N Engl J Med 2004;351:1493-501 98 Gurm HS, Yadav JS, Fayad P, et al Long-term results of carotid stenting versus endarterectomy in high-risk patients N Engl J Med 2008;358:1572-9 99 Mas JL, Chatellier G, Beyssen B, Beyssen B, et al Endarterectomy versus stenting in patients with symptomatic severe carotid stenosis N Engl J Med 2006;355:1660-71 100 Ringleb PA, Allenberg J, Bruckmann H, et al 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial Lancet 2006;368:1239-47 166 Curr Probl Cardiol, April 2012 101 Ederle J, Dobson J, Featherstone RL, et al Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial Lancet 2010;375:985-97 102 Brott TG, Hobson RW 2nd, Howard G, et al Stenting versus endarterectomy for treatment of carotid-artery stenosis N Engl J Med 2010;363:11-23 103 Cohen DJ, Stolker JM, Wang K, et al Health-related quality of life after carotid stenting versus carotid endarterectomy: results from CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) J Am Coll Cardiol 2011;58:1557-65 104 Kertai MD, Boersma E, Klein J, et al Long-term prognostic value of asymptomatic cardiac troponin T elevations in patients after major vascular surgery Eur J Vasc Endovasc Surg 2004;28:59-66 105 Landesberg G, Shatz V, Akopnik I, et al Association of cardiac troponin, CK-MB, and postoperative myocardial ischemia with long-term survival after major vascular surgery J Am Coll Cardiol 2003;42:1547-54 106 Nienhuis MB, Ottervanger JP, Bilo HJ, et al Prognostic value of troponin after elective percutaneous coronary intervention: A meta-analysis Catheter Cardiovasc Interv 2008;71:318-24 107 Oscarsson A, Eintrei C, Anskär S, et al Troponin T-values provide long-term prognosis in elderly patients undergoing non-cardiac surgery Acta Anaesthesiol Scand 2004;48:1071-9 108 Blackshear JL, Cutlip DE, Roubin GS, et al Myocardial infarction after carotid stenting and endarterectomy: results from the carotid revascularization endarterectomy versus stenting trial Circulation 2011;123:2571-8 109 Acculink RX Carotid Stent System standard surgical risk indication P040012/ S034 Abbott Vascular presentation to the Food and Drug Administration Circulatory System Devices Advisory Panel 2011, January 26 Available at: http:// www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Medical Devices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/UCM 248647.pdf Accessed October 18, 2011 110 Executive Committee for the Asymptomatic Carotid Atherosclerosis Study Endarterectomy for asymptomatic carotid artery stenosis JAMA 1995;273:1421-8 111 Bettmann MA, Katzen BT, Whisnant J, et al Carotid stenting and angioplasty: a statement for healthcare professionals from the Councils on cardiovascular Radiology, Stroke, cardio-thoracic and Vascular Surgery, Epidemiology and Prevention, and Clinical Cardiology, American Heart Association Stroke 1998;29:336-8 112 Abbott announces 30-day results of clinical trial for carotid artery stent and filter system (Company News) Angioplastyorg http://wwwptcaorg/pr_abbott/20030919html Accessed October 18, 2011 113 Gray WA, Hopkins LN, Yadav S, et al Protected carotid stenting in high-surgicalrisk patients: the Archer results J Vasc Surg 2006;44:258-68 114 Iyer SS, White CJ, Hopkins LN, et al Carotid artery revascularization in high-surgical-risk patients using the Carotid WALLSTENT and FilterWire EX/EZ: 1-year outcomes in the BEACH Pivotal Group J Am Coll Cardiol 2008;51:427-34 115 Higashida RT, Popma JJ, Apruzzese P, et al Evaluation of the Medtronic exponent self-expanding carotid stent system with the Medtronic guardwire temporary occlusion Curr Probl Cardiol, April 2012 167 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 168 and aspiration system in the treatment of carotid stenosis: combined from the MAVErIC (Medtronic AVE self-expanding CaRotid Stent System with distal protection in the treatment of Carotid stenosis) I and MAVErIC II trials Stroke 2010;41:e102-9 Hopkins LN, Myla S, Grube E, et al Carotid artery revascularization in high surgical risk patients with the NexStent and the Filterwire EX/EZ: 1-year results in the CABERNET trial Catheter Cardiovasc Interv 2008;71:950-60 Safian RD, Bresnahan JF, Jaff MR, et al Protected carotid stenting in high-risk patients with severe carotid artery stenosis J Am Coll Cardiol 2006;47:2384-9 Katzen BT, Criado FJ, Ramee SR, et al Carotid artery stenting with emboli protection surveillance study: thirty-day results of the CASES-PMS study Catheter Cardiovasc Interv 2007;70:316-23 Gray WA, Yadav JS, Verta P, et al The CAPTURE registry: results of carotid stenting with embolic protection in the post approval setting Catheter Cardiovasc Interv 2007;69:341-8 Gray WA, Chaturvedi S, Verta P, et al Thirty-day outcomes for carotid artery stenting in 6320 patients from prospective, multicenter, high-surgical-risk registries Circ Cardiovasc Interv 2009;2:159-66 Clair DG, Hopkins LN, Mehta M, et al Neuroprotection during carotid artery stenting using the GORE flow reversal system: 30-day outcomes in the EMPiRE Clinical Study Catheter Cardiovasc Interv 2011;77:420-9 Myla S, Bacharach JM, Ansel GM, et al Carotid artery stenting in high surgical risk patients using the FiberNet embolic protection system: the EPIC trial results Catheter Cardiovasc Interv 2010;75:817-22 Garg N, Karagiorgos N, Pisimisis GT, et al Cerebral protection devices reduce periprocedural strokes during carotid angioplasty and stenting: a systematic review of the current literature J Endovasc Ther 2009;16:412-27 Moulakakis KG, Mylonas SN, Sfyroeras GS, et al Hyperperfusion syndrome after carotid revascularization J Vasc Surg 2009;49:1060-8 Chang CH, Chang TY, Chang YJ, et al The role of perfusion computed tomography in the prediction of cerebral hyperperfusion syndrome PLoS ONE 2011;6:e19886 Tseng YC, Hsu HL, Lee TH, et al Prediction of cerebral hyperperfusion syndrome after carotid stenting: a cerebral perfusion computed tomography study J Comput Assist Tomogr 2009;33:540-5 Halliday A, Mansfield A, Marro J, et al Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial Lancet 2004;363:1491-502 Brooks WH, McClure RR, Jones MR, et al Carotid angioplasty and stenting versus carotid endarterectomy for treatment of asymptomatic carotid stenosis: a randomized trial in a community hospital Neurosurgery 2004;54:318-25 Mantese VA, Timaran CH, Chiu D, et al The Carotid revascularization Endarterectomy versus Stenting Trial (CREST): stenting versus carotid endarterectomy for carotid disease Stroke 2010;41:S31-4 Reiff T, Stingele R, Eckstein HH, et al Stent-protected angioplasty in asymptomatic carotid artery stenosis vs endarterectomy: SPACE2—a three-arm randomisedcontrolled clinical trial Int J Stroke 2009;4:294-9 Curr Probl Cardiol, April 2012 131 Reiff T, Böckler D, Böhm M, et al Ongoing randomized controlled trials comparing interventional methods and optimal medical treatment in the treatment of asymptomatic carotid stenosis Stroke 2010;41:e605-6 [Author reply e607] 132 Woo K, Garg J, Hye RJ, et al Contemporary results of carotid endarterectomy for asymptomatic carotid stenosis Stroke 2010;41:975-9 133 Abbott AL, Chambers BR, Stork JL, et al Embolic signals and prediction of ipsilateral stroke or transient ischemic attack in asymptomatic carotid stenosis: a multicenter prospective cohort study Stroke 2005;36:1128-33 134 Marquardt L, Geraghty OC, Mehta Z, et al Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study Stroke 2010;41:e11-7 135 Goessens BM, Visseren FL, Kappelle LJ, et al Asymptomatic carotid artery stenosis and the risk of new vascular events in patients with manifest arterial disease: the SMART study Stroke 2007;38:1470-5 Curr Probl Cardiol, April 2012 169 ...Prevalence of Carotid Artery Stenosis he prevalence of carotid artery stenosis varies with age, gender, and symptomatic status Each year,... 80% are ischemic.1 Symptomatic carotid stenosis is implicated in 15% to 30% of all ischemic strokes.2,3 The reported prevalence of asymptomatic carotid artery stenosis of 50% or greater in patients... minor degree of stenosis Certain special situations exist in which peak systolic velocities may not reflect accurately the severity of carotid artery stenosis For example, when the stenosis exceeds