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THEMED ARTICLE y Vascular Disease
Special Report
Optimal management of patients with symptomatic and asymptomatic carotid artery stenosis: work in progress Expert Rev. Cardiovasc. Ther. 12(4), 437–441 (2014)
Kosmas I Paraskevas*1, Anne L Abbott2 and Frank J Veith3 1 Department of Vascular Surgery, Larissa University Hospital, Larissa, Greece 2 School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia 3 Divisions of Vascular Surgery, The Cleveland Clinic and New York University Langone Medical Center, New York, NY, USA *Author for correspondence: [email protected]
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The optimal management of patients with symptomatic and asymptomatic carotid artery stenosis remains a subject of extensive debate. Several international societies and associations have published guidelines for the management of carotid patients. Although these recommendations are based on the same randomized trials, differences in interpretation of available knowledge have often led to different (or even conflicting) recommendations. This special report summarizes the current evidence-based optimal management of patients with symptomatic and asymptomatic carotid stenosis and compares key international guidelines. Finally, issues requiring further research are identified and discussed. KEYWORDS: carotid artery stenosis • carotid artery stenting • carotid endarterectomy • stroke • transient ischemic attack
In 2011, the American College of Cardiology/ American Heart Association (ACC/AHA) guideline (endorsed by 12 other Associations) recommended carotid artery stenting (CAS) as an ‘alternative’ to carotid endarterectomy (CEA) for the management of symptomatic patients at average or low endovascular risk with >70% carotid stenosis as documented by noninvasive imaging or >50% carotid stenosis as documented by catheter angiography (class I; level of evidence B). In this guideline, ‘class I’ meant CAS ‘should be performed’ as the benefits strongly outweigh the risks, while ‘level of evidence B’ meant the recommendation is derived from a single randomized trial or nonrandomized studies [1]. However, ‘level of evidence B’ ‘did not mean the recommendation was weak’ because many important clinical questions do not lend themselves to clinical trials [1]. These guidelines also gave a ‘class IIb, level of evidence B’ recommendation for prophylactic CAS in patients with >60% (by angiography) or >70% (by validated Doppler ultrasound) asymptomatic carotid artery stenosis [1]. The ‘class IIb’ recommendation meant 10.1586/14779072.2014.893826
CAS ‘may be considered’ for patient management as the benefits are at least equal to the risks and that additional studies are needed [1]. These ACC/AHA recommendations are considerably different from those of other national or international societies [2–4] and at odds with aspects of the evidence base. For instance, according to the revised Society for Vascular Surgery guidelines [2], CEA is preferred to CAS in most symptomatic patients with carotid stenosis (class I; level of evidence B). CAS is preferred over CEA in specific symptomatic patients, namely, those with tracheal stoma, scarred necks from prior ipsilateral surgery or external beam radiotherapy, prior cranial nerve injury and lesions that extend proximal to the clavicle or distal to the C2 vertebral body (grade II; level of evidence B), as well as in patients with severe uncorrectable coronary artery disease, congestive heart failure or chronic obstructive pulmonary disease (grade II; level of evidence C) [2]. Differences in interpretation of available knowledge may cause confusion regarding the management of patients with carotid stenosis.
2014 Informa UK Ltd
ISSN 1477-9072
437
Special Report
Paraskevas, Abbott & Veith
This article summarizes the current evidence-based optimal management of patients with symptomatic and asymptomatic carotid stenosis and compares key international guidelines. Finally, issues requiring further research are identified and discussed.
Expert Review of Cardiovascular Therapy Downloaded from informahealthcare.com by Michigan University on 10/18/14 For personal use only.
Patients with symptomatic carotid artery stenosis
Several major guidelines, including the 2011 ACC/AHA guideline, recommend CEA for patients with symptomatic 70–99% internal carotid artery stenosis, if patients are considered at low or average surgical risk (class I; level of evidence A or B) [1–5]. CEA should ideally be performed within 2 weeks or as soon as possible following the cerebrovascular event (stroke, transient ischemic attack or amaurosis fugax) [1–5]. Emerging evidence suggests that CEA performed within 48 h after the cerebrovascular event may be associated with additional recurrent stroke prevention benefits [6]. In addition, guidelines recommend all symptomatic patients should be placed on current best medical treatment (BMT), generally consisting of encouraging smoking cessation, weight optimization, regular exercise, antiplatelet therapy and optimal blood pressure, glycemic and lipid control (including statins). The ACC/AHA guideline [1], an AHA/American Stroke Association guideline (class I; level of evidence B) [5] and, with lesser conviction, the European Society of Cardiology guideline (class IIB; level of evidence B [7]) have recommended CAS as an ‘alternative’ to CEA for the treatment of symptomatic carotid stenosis. These recommendations, which are based largely on the results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) [8], have been viewed with growing concern [9–11]. The problem is that ‘alternative’ may be easily viewed as meaning that CAS is an ‘equivalent’ option to CEA for the management of symptomatic patients [10]. However, based on available evidence, CAS should not be viewed as an ‘equivalent’ option. Even in the best academic centers, rates of stroke and stroke/death associated with CAS in symptomatic patients are about double to those compared with CEA [9,11–13]. These differential rates are three-times higher within 7 days of symptoms [14], 2.5-times higher in women (at least in CREST) [12,15] and 2.5-times higher in patients over 70 years of age [16]. Additionally, CAS has no stroke prevention advantage in symptomatic patients £65–70 years of age [12,16–18]. Although periprocedural rates of myocardial infarction (MI) have been used by some to argue clinical equivalence between CEA and CAS [19], this rational is highly questionable. MI is a safety outcome, not an efficacy outcome. Moreover, in past randomized trials, 30-day periprocedural strokes (which were more commonly caused by CAS) were about four-times more common than 30-day periprocedural clinically defined MIs. Even if 30-day periprocedural MIs are included with 30-day stroke or death rates as a primary outcome measure, a metaanalysis of all past randomized trials (including CREST) showed that for symptomatic patients the results still favored CEA (odds ratio: 1.49; 95% CI: 1.15–1.80; p = 0.002) [12]. 438
With better patient selection, improvements in CAS technology and expertise and centralization of CAS procedures, CAS may become an ‘alternative’ to CEA for selected symptomatic patients in the future [10]. With the possible exception of centers of CAS excellence, this is not currently the case [13]. CAS may be a sensible choice over CEA in symptomatic patients with severe comorbidities (such as severe uncorrectable coronary heart disease, congestive heart failure or chronic obstructive pulmonary disease) [1,2,5]. In addition, CAS has been recommended over CEA in certain symptomatic patients with >50% stenosis who are considered at high surgical risk for anatomical reasons, such as those with tracheal stoma, prior cranial nerve injury or scarred necks from radiotherapy or surgery [1–3,5]. However, emerging evidence suggests that CAS may not be preferable over CEA for patients with carotid stenosis after previous cervical radiation therapy [20]. A recent systematic review and meta-analysis on patients undergoing a carotid revascularization procedure after previous cervical radiation therapy showed higher rates of cerebrovascular adverse events (p = 0.014) and higher restenosis rates (p < 0.003) when CAS was compared with CEA [20]. In addition, there are no trial data that establish a stroke prevention advantage of CAS over CEA or for either procedure over BMT alone in such high surgical risk patients [11]. Such patients were generally excluded from previous adequately powered trials. Using past randomized trial results, symptomatic patients are most likely to benefit from CEA if their expected survival is at least 3 years [21]. Finally, the landmark randomized CEA trials that demonstrated a stroke prevention benefit of CEA over BMT alone for selected patients with symptomatic carotid stenosis employed medical treatments, which are now considered outdated [11,22]. In addition, the £6% 30-day periprocedural risk of stroke or death considered to confer an overall procedural stroke prevention benefit is now considered too high [11]. Thus, a leading priority is to perform research to better risk stratify symptomatic patients and to examine if the recommendations based on the landmark randomized CEA trials still apply using today’s practice standards. The Second European Carotid Surgery Trial is a welcome start in this regard [23]. Patients with asymptomatic carotid artery stenosis
The optimal stroke prevention management of patients with asymptomatic carotid artery stenosis has been a subject of extensive debate [24–28]. The justification for CEA for patients with asymptomatic carotid artery stenosis was based on the results of the Asymptomatic Carotid Atherosclerosis Study [29], the Asymptomatic Carotid Surgery Trial [30] and to a lesser extent the Veterans Affairs Cooperative Study [31] showing that, compared with BMT alone, CEA plus BMT reduced the average annual stroke rate by 0.5–1.0% in patients with 50–99% or 60–99% asymptomatic carotid artery stenosis. Patients were entered into these two trials between 1983 and 2003 [29–31]. Medical treatment at that time consisted of risk factor identification and modification, which usually included hypertension and aspirin therapy, although an increasing number of patients Expert Rev. Cardiovasc. Ther. 12(4), (2014)
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Optimal management of patients with symptomatic & asymptomatic CAS
in the Asymptomatic Carotid Surgery Trial were also subsequently given statins [30]. However, since recruitment began in these trials, definition of heart and vascular disease risk factors have become more sensitive, more patients have stopped smoking and new and more effective drugs, including statins, have become increasingly used in patients with carotid stenosis [24]. Several international groups have now reported falls in average annual rate of ipsilateral stroke by up to 80% with medical treatment alone since the early 1980s to a level of about 1.0% or less [24–27,32,33]. Because of this, a mass surgical approach for asymptomatic carotid artery disease has been challenged and some questioned the need for any invasive procedure in most, if not all, asymptomatic patients [24–27,32,33]. Nevertheless, CEA may be justified in asymptomatic patients at high risk for a future cerebrovascular event, despite receiving current BMT. These high-risk patient groups remain to be clearly defined, and reliable risk stratification methods are required. Promising preliminary risk stratification results have come from examining silent embolic infarcts on brain CT scans [34], a combination of clinical characteristics and ultrasonic plaque characteristics [35], the presence of carotid plaque ulceration on 3D ultrasound [36] and a combination of ultrasonic plaque echolucency and microemboli on transcranial Doppler [37]. However, the use of transcranial Doppler embolus detection alone as a means to identify high ipsilateral stroke risk asymptomatic patients remains controversial, with several unresolved issues [38,39]. Although some guidelines give recommendations for CAS in asymptomatic patients [1,7], others clearly state that there is currently no evidence to support routine CAS in these patients [2,40]. This is because available data indicate the likelihood of higher stroke rates with CAS compared with CEA, as has already been found in symptomatic patients [9,11]. Despite the absence of adequately powered randomized trials of CAS versus CEA in asymptomatic patients, the direction of effect was toward twice the risk of stroke or death in the largest and most relevant trial, CREST [8]. In addition, CAS has been associated with significantly higher rates of stroke and death in large registries of asymptomatic patients [41–43]. Future trials should aim at developing risk stratification systems able to identify asymptomatic patients with sufficiently high ipsilateral stroke risk, despite current BMT alone. Once these asymptomatic patients have been reliably identified, randomized trials of additional procedures should investigate if and to what extent these procedures provide an overall stroke prevention benefit. The future in carotid revascularization will use pre-intervention parameters that will reduce the number of interventions in symptomatic patients and hopefully will identify the percentage of asymptomatic patients who really have a high risk for stroke and will therefore benefit from a carotid revascularization procedure. Meanwhile, randomized controlled trials comparing the outcomes of CEA versus CAS versus BMT alone in relatively nonrisk stratified patients with asymptomatic carotid stenosis are planned or already under way [44–46]. Their results are not informahealthcare.com
Special Report
expected soon. Thus, some uncertainty in this area will continue. Until the availability of new evidence, current BMT is probably indicated for all asymptomatic patients and those who are considered at high ipsilateral stroke risk despite current BMT should be referred to appropriate studies. Conclusion
Patients with symptomatic carotid stenosis who are considered at low or average surgical risk should receive current BMT (including appropriate antiplatelet and statin therapy) plus CEA as soon as possible after the index event [1–5]. CEA is preferred over CAS in such patients. CAS may be considered for those symptomatic patients who are at high surgical risk or in whom CEA is contraindicated. However, good measurements of stroke risk according to intervention strategy (BMT alone vs additional CEA or CAS) are needed for these high-risk subgroups. For asymptomatic patients, all should be placed on current BMT. Offering routine CEA to asymptomatic patients is currently inappropriate. Future trials should investigate whether or not CEA has a role in specific asymptomatic subgroups at high ipsilateral stroke risk, despite receiving current BMT. Differences in grading systems might explain some of the apparent differences in the recommendations between the various guidelines. Use of a specific grading system may help resolve some of these conflicting recommendations. Research to address current uncertainties regarding optimal management of carotid stenosis is much needed and, if performed well, will be cost-effective given that carotid artery disease is a major public health concern. Improvements in CAS technology (better access techniques, embolic protection and stents) and more targeted patient selection may justify the procedure’s increased usage in the future. An additional priority is to organize routine practice so that real-world patient outcomes (including 30-day procedural rates of stroke or death) are reliably measured wherever carotid procedures are performed. Evidence gained from routine clinical practice will complement that obtained from other research settings. Expert commentary
The optimal management of patients with symptomatic and asymptomatic carotid artery stenosis is still debatable. Current evidence suggests that CEA plus BMT comprises the treatment-of-choice for the majority of patients with symptomatic carotid artery stenosis. CAS may be indicated for specific symptomatic patients, namely those at high-risk for surgery or in whom CEA is contraindicated. For asymptomatic patients, all should be placed on current BMT. Future research should aim to identify the percentage of asymptomatic patients at high risk for stroke despite BMT who will possibly benefit from a carotid revascularization procedure. Five-year view
Most controversies in the management of patients with asymptomatic carotid artery stenosis will hopefully be resolved in 5 years. The results of randomized controlled trials investigating 439
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Paraskevas, Abbott & Veith
the results of CEA versus CAS versus BMT alone for asymptomatic patients will hopefully be published. These will help guide clinical practice and accurately define the optimal management of these patients. Furthermore, improvements in CAS equipment and expertise may lead to improved results. CAS may then prove to be equivalent with (or even superior to) CEA for the management of specific symptomatic patients.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.
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Key issues • The optimal management of patients with symptomatic and asymptomatic carotid stenosis is currently debatable. • Carotid endarterectomy plus best medical treatment (BMT) comprise the treatment-of-choice for the majority of symptomatic patients, while carotid artery stenting should be reserved for those symptomatic patients at high risk for surgery or in whom surgery is contraindicated. • All asymptomatic patients should be placed on current BMT. • For some asymptomatic patients, current BMT alone may not be adequate for stroke prevention. • Research should aim to identify those asymptomatic patients at high risk for stroke despite current BMT and initiate trials to investigate, if these patients will benefit from an additional carotid revascularization procedure.
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THEMED ARTICLE y Vascular Disease
Special Report
Optimal management of patients with symptomatic and asymptomatic carotid artery stenosis: work in progress Expert Rev. Cardiovasc. Ther. 12(4), 437–441 (2014)
Kosmas I Paraskevas*1, Anne L Abbott2 and Frank J Veith3 1 Department of Vascular Surgery, Larissa University Hospital, Larissa, Greece 2 School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia 3 Divisions of Vascular Surgery, The Cleveland Clinic and New York University Langone Medical Center, New York, NY, USA *Author for correspondence: [email protected]
informahealthcare.com
The optimal management of patients with symptomatic and asymptomatic carotid artery stenosis remains a subject of extensive debate. Several international societies and associations have published guidelines for the management of carotid patients. Although these recommendations are based on the same randomized trials, differences in interpretation of available knowledge have often led to different (or even conflicting) recommendations. This special report summarizes the current evidence-based optimal management of patients with symptomatic and asymptomatic carotid stenosis and compares key international guidelines. Finally, issues requiring further research are identified and discussed. KEYWORDS: carotid artery stenosis • carotid artery stenting • carotid endarterectomy • stroke • transient ischemic attack
In 2011, the American College of Cardiology/ American Heart Association (ACC/AHA) guideline (endorsed by 12 other Associations) recommended carotid artery stenting (CAS) as an ‘alternative’ to carotid endarterectomy (CEA) for the management of symptomatic patients at average or low endovascular risk with >70% carotid stenosis as documented by noninvasive imaging or >50% carotid stenosis as documented by catheter angiography (class I; level of evidence B). In this guideline, ‘class I’ meant CAS ‘should be performed’ as the benefits strongly outweigh the risks, while ‘level of evidence B’ meant the recommendation is derived from a single randomized trial or nonrandomized studies [1]. However, ‘level of evidence B’ ‘did not mean the recommendation was weak’ because many important clinical questions do not lend themselves to clinical trials [1]. These guidelines also gave a ‘class IIb, level of evidence B’ recommendation for prophylactic CAS in patients with >60% (by angiography) or >70% (by validated Doppler ultrasound) asymptomatic carotid artery stenosis [1]. The ‘class IIb’ recommendation meant 10.1586/14779072.2014.893826
CAS ‘may be considered’ for patient management as the benefits are at least equal to the risks and that additional studies are needed [1]. These ACC/AHA recommendations are considerably different from those of other national or international societies [2–4] and at odds with aspects of the evidence base. For instance, according to the revised Society for Vascular Surgery guidelines [2], CEA is preferred to CAS in most symptomatic patients with carotid stenosis (class I; level of evidence B). CAS is preferred over CEA in specific symptomatic patients, namely, those with tracheal stoma, scarred necks from prior ipsilateral surgery or external beam radiotherapy, prior cranial nerve injury and lesions that extend proximal to the clavicle or distal to the C2 vertebral body (grade II; level of evidence B), as well as in patients with severe uncorrectable coronary artery disease, congestive heart failure or chronic obstructive pulmonary disease (grade II; level of evidence C) [2]. Differences in interpretation of available knowledge may cause confusion regarding the management of patients with carotid stenosis.
2014 Informa UK Ltd
ISSN 1477-9072
437
Special Report
Paraskevas, Abbott & Veith
This article summarizes the current evidence-based optimal management of patients with symptomatic and asymptomatic carotid stenosis and compares key international guidelines. Finally, issues requiring further research are identified and discussed.
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Patients with symptomatic carotid artery stenosis
Several major guidelines, including the 2011 ACC/AHA guideline, recommend CEA for patients with symptomatic 70–99% internal carotid artery stenosis, if patients are considered at low or average surgical risk (class I; level of evidence A or B) [1–5]. CEA should ideally be performed within 2 weeks or as soon as possible following the cerebrovascular event (stroke, transient ischemic attack or amaurosis fugax) [1–5]. Emerging evidence suggests that CEA performed within 48 h after the cerebrovascular event may be associated with additional recurrent stroke prevention benefits [6]. In addition, guidelines recommend all symptomatic patients should be placed on current best medical treatment (BMT), generally consisting of encouraging smoking cessation, weight optimization, regular exercise, antiplatelet therapy and optimal blood pressure, glycemic and lipid control (including statins). The ACC/AHA guideline [1], an AHA/American Stroke Association guideline (class I; level of evidence B) [5] and, with lesser conviction, the European Society of Cardiology guideline (class IIB; level of evidence B [7]) have recommended CAS as an ‘alternative’ to CEA for the treatment of symptomatic carotid stenosis. These recommendations, which are based largely on the results of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) [8], have been viewed with growing concern [9–11]. The problem is that ‘alternative’ may be easily viewed as meaning that CAS is an ‘equivalent’ option to CEA for the management of symptomatic patients [10]. However, based on available evidence, CAS should not be viewed as an ‘equivalent’ option. Even in the best academic centers, rates of stroke and stroke/death associated with CAS in symptomatic patients are about double to those compared with CEA [9,11–13]. These differential rates are three-times higher within 7 days of symptoms [14], 2.5-times higher in women (at least in CREST) [12,15] and 2.5-times higher in patients over 70 years of age [16]. Additionally, CAS has no stroke prevention advantage in symptomatic patients £65–70 years of age [12,16–18]. Although periprocedural rates of myocardial infarction (MI) have been used by some to argue clinical equivalence between CEA and CAS [19], this rational is highly questionable. MI is a safety outcome, not an efficacy outcome. Moreover, in past randomized trials, 30-day periprocedural strokes (which were more commonly caused by CAS) were about four-times more common than 30-day periprocedural clinically defined MIs. Even if 30-day periprocedural MIs are included with 30-day stroke or death rates as a primary outcome measure, a metaanalysis of all past randomized trials (including CREST) showed that for symptomatic patients the results still favored CEA (odds ratio: 1.49; 95% CI: 1.15–1.80; p = 0.002) [12]. 438
With better patient selection, improvements in CAS technology and expertise and centralization of CAS procedures, CAS may become an ‘alternative’ to CEA for selected symptomatic patients in the future [10]. With the possible exception of centers of CAS excellence, this is not currently the case [13]. CAS may be a sensible choice over CEA in symptomatic patients with severe comorbidities (such as severe uncorrectable coronary heart disease, congestive heart failure or chronic obstructive pulmonary disease) [1,2,5]. In addition, CAS has been recommended over CEA in certain symptomatic patients with >50% stenosis who are considered at high surgical risk for anatomical reasons, such as those with tracheal stoma, prior cranial nerve injury or scarred necks from radiotherapy or surgery [1–3,5]. However, emerging evidence suggests that CAS may not be preferable over CEA for patients with carotid stenosis after previous cervical radiation therapy [20]. A recent systematic review and meta-analysis on patients undergoing a carotid revascularization procedure after previous cervical radiation therapy showed higher rates of cerebrovascular adverse events (p = 0.014) and higher restenosis rates (p < 0.003) when CAS was compared with CEA [20]. In addition, there are no trial data that establish a stroke prevention advantage of CAS over CEA or for either procedure over BMT alone in such high surgical risk patients [11]. Such patients were generally excluded from previous adequately powered trials. Using past randomized trial results, symptomatic patients are most likely to benefit from CEA if their expected survival is at least 3 years [21]. Finally, the landmark randomized CEA trials that demonstrated a stroke prevention benefit of CEA over BMT alone for selected patients with symptomatic carotid stenosis employed medical treatments, which are now considered outdated [11,22]. In addition, the £6% 30-day periprocedural risk of stroke or death considered to confer an overall procedural stroke prevention benefit is now considered too high [11]. Thus, a leading priority is to perform research to better risk stratify symptomatic patients and to examine if the recommendations based on the landmark randomized CEA trials still apply using today’s practice standards. The Second European Carotid Surgery Trial is a welcome start in this regard [23]. Patients with asymptomatic carotid artery stenosis
The optimal stroke prevention management of patients with asymptomatic carotid artery stenosis has been a subject of extensive debate [24–28]. The justification for CEA for patients with asymptomatic carotid artery stenosis was based on the results of the Asymptomatic Carotid Atherosclerosis Study [29], the Asymptomatic Carotid Surgery Trial [30] and to a lesser extent the Veterans Affairs Cooperative Study [31] showing that, compared with BMT alone, CEA plus BMT reduced the average annual stroke rate by 0.5–1.0% in patients with 50–99% or 60–99% asymptomatic carotid artery stenosis. Patients were entered into these two trials between 1983 and 2003 [29–31]. Medical treatment at that time consisted of risk factor identification and modification, which usually included hypertension and aspirin therapy, although an increasing number of patients Expert Rev. Cardiovasc. Ther. 12(4), (2014)
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Optimal management of patients with symptomatic & asymptomatic CAS
in the Asymptomatic Carotid Surgery Trial were also subsequently given statins [30]. However, since recruitment began in these trials, definition of heart and vascular disease risk factors have become more sensitive, more patients have stopped smoking and new and more effective drugs, including statins, have become increasingly used in patients with carotid stenosis [24]. Several international groups have now reported falls in average annual rate of ipsilateral stroke by up to 80% with medical treatment alone since the early 1980s to a level of about 1.0% or less [24–27,32,33]. Because of this, a mass surgical approach for asymptomatic carotid artery disease has been challenged and some questioned the need for any invasive procedure in most, if not all, asymptomatic patients [24–27,32,33]. Nevertheless, CEA may be justified in asymptomatic patients at high risk for a future cerebrovascular event, despite receiving current BMT. These high-risk patient groups remain to be clearly defined, and reliable risk stratification methods are required. Promising preliminary risk stratification results have come from examining silent embolic infarcts on brain CT scans [34], a combination of clinical characteristics and ultrasonic plaque characteristics [35], the presence of carotid plaque ulceration on 3D ultrasound [36] and a combination of ultrasonic plaque echolucency and microemboli on transcranial Doppler [37]. However, the use of transcranial Doppler embolus detection alone as a means to identify high ipsilateral stroke risk asymptomatic patients remains controversial, with several unresolved issues [38,39]. Although some guidelines give recommendations for CAS in asymptomatic patients [1,7], others clearly state that there is currently no evidence to support routine CAS in these patients [2,40]. This is because available data indicate the likelihood of higher stroke rates with CAS compared with CEA, as has already been found in symptomatic patients [9,11]. Despite the absence of adequately powered randomized trials of CAS versus CEA in asymptomatic patients, the direction of effect was toward twice the risk of stroke or death in the largest and most relevant trial, CREST [8]. In addition, CAS has been associated with significantly higher rates of stroke and death in large registries of asymptomatic patients [41–43]. Future trials should aim at developing risk stratification systems able to identify asymptomatic patients with sufficiently high ipsilateral stroke risk, despite current BMT alone. Once these asymptomatic patients have been reliably identified, randomized trials of additional procedures should investigate if and to what extent these procedures provide an overall stroke prevention benefit. The future in carotid revascularization will use pre-intervention parameters that will reduce the number of interventions in symptomatic patients and hopefully will identify the percentage of asymptomatic patients who really have a high risk for stroke and will therefore benefit from a carotid revascularization procedure. Meanwhile, randomized controlled trials comparing the outcomes of CEA versus CAS versus BMT alone in relatively nonrisk stratified patients with asymptomatic carotid stenosis are planned or already under way [44–46]. Their results are not informahealthcare.com
Special Report
expected soon. Thus, some uncertainty in this area will continue. Until the availability of new evidence, current BMT is probably indicated for all asymptomatic patients and those who are considered at high ipsilateral stroke risk despite current BMT should be referred to appropriate studies. Conclusion
Patients with symptomatic carotid stenosis who are considered at low or average surgical risk should receive current BMT (including appropriate antiplatelet and statin therapy) plus CEA as soon as possible after the index event [1–5]. CEA is preferred over CAS in such patients. CAS may be considered for those symptomatic patients who are at high surgical risk or in whom CEA is contraindicated. However, good measurements of stroke risk according to intervention strategy (BMT alone vs additional CEA or CAS) are needed for these high-risk subgroups. For asymptomatic patients, all should be placed on current BMT. Offering routine CEA to asymptomatic patients is currently inappropriate. Future trials should investigate whether or not CEA has a role in specific asymptomatic subgroups at high ipsilateral stroke risk, despite receiving current BMT. Differences in grading systems might explain some of the apparent differences in the recommendations between the various guidelines. Use of a specific grading system may help resolve some of these conflicting recommendations. Research to address current uncertainties regarding optimal management of carotid stenosis is much needed and, if performed well, will be cost-effective given that carotid artery disease is a major public health concern. Improvements in CAS technology (better access techniques, embolic protection and stents) and more targeted patient selection may justify the procedure’s increased usage in the future. An additional priority is to organize routine practice so that real-world patient outcomes (including 30-day procedural rates of stroke or death) are reliably measured wherever carotid procedures are performed. Evidence gained from routine clinical practice will complement that obtained from other research settings. Expert commentary
The optimal management of patients with symptomatic and asymptomatic carotid artery stenosis is still debatable. Current evidence suggests that CEA plus BMT comprises the treatment-of-choice for the majority of patients with symptomatic carotid artery stenosis. CAS may be indicated for specific symptomatic patients, namely those at high-risk for surgery or in whom CEA is contraindicated. For asymptomatic patients, all should be placed on current BMT. Future research should aim to identify the percentage of asymptomatic patients at high risk for stroke despite BMT who will possibly benefit from a carotid revascularization procedure. Five-year view
Most controversies in the management of patients with asymptomatic carotid artery stenosis will hopefully be resolved in 5 years. The results of randomized controlled trials investigating 439
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Paraskevas, Abbott & Veith
the results of CEA versus CAS versus BMT alone for asymptomatic patients will hopefully be published. These will help guide clinical practice and accurately define the optimal management of these patients. Furthermore, improvements in CAS equipment and expertise may lead to improved results. CAS may then prove to be equivalent with (or even superior to) CEA for the management of specific symptomatic patients.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.
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Key issues • The optimal management of patients with symptomatic and asymptomatic carotid stenosis is currently debatable. • Carotid endarterectomy plus best medical treatment (BMT) comprise the treatment-of-choice for the majority of symptomatic patients, while carotid artery stenting should be reserved for those symptomatic patients at high risk for surgery or in whom surgery is contraindicated. • All asymptomatic patients should be placed on current BMT. • For some asymptomatic patients, current BMT alone may not be adequate for stroke prevention. • Research should aim to identify those asymptomatic patients at high risk for stroke despite current BMT and initiate trials to investigate, if these patients will benefit from an additional carotid revascularization procedure.
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Medicare and Medicaid Services (CMS) should not extend reimbursement indications for carotid artery angioplasty/ stenting. Eur J Vasc Endovasc Surg 2012; 43(3):247-51
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