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Year : 2022  |  Volume : 25  |  Issue : 2  |  Page : 171-176

Asymptomatic carotid stenosis: Several guidelines with unclear answers

Department of Neurology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission19-Jun-2021
Date of Acceptance01-Sep-2021
Date of Web Publication13-Jan-2022

Correspondence Address:
Deepti Vibha
Room No 707, 7th Floor, Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, New Delhi - 110 049
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.aian_566_21

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How to cite this article:
Sudheer P, Vibha D, Misra S. Asymptomatic carotid stenosis: Several guidelines with unclear answers. Ann Indian Acad Neurol 2022;25:171-6

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Sudheer P, Vibha D, Misra S. Asymptomatic carotid stenosis: Several guidelines with unclear answers. Ann Indian Acad Neurol [serial online] 2022 [cited 2023 Feb 5];25:171-6. Available from:

Asymptomatic carotid stenosis (ACS) is commonly defined as the presence of atherosclerotic narrowing of the proximal internal carotid artery by ≥50% at the level of bifurcation in individuals with no history of recent (within the last six months) ischemic stroke/TIA involving ipsilateral carotid territory.[1] Although the presence of 50%–69% narrowing is considered as moderate stenosis, narrowing ≥70% is generally considered as severe stenosis.[2] However, there are no standard criteria proposed on the severity of stenosis and duration of recent ischemic event and definitions vary among studies depending on the method used for assessment of stenosis. Some criteria also use >60% definition. [Table 1] summarises the definitions of all major trials addressing the management of ACS.
Table 1: Definitions of asymptomatic carotid stenosis used in major studies

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The importance of optimal management ACS comes from the fact that it is not just a risk factor for stroke but to coronary artery disease and mortality as well. Results from the Second Manifestations of ARTerial disease (SMART) study provides evidence that patients with ACS should be treated optimally as they are at risk of vascular events (HR 1.5; 95% CI 1.1–2.1) and mortality (HR 1.8; 95% CI 1.2–2.6).[8] However, the management of ACS remains controversial, largely because only a small proportion of patients are ever destined to suffer a stroke, along with growing evidence that the risk of stroke declines with modern medical therapy, risk factors control and statin use.

   What Do the Guidelines Say? Top

A significant controversy in the management of patients with ACS is the selection of patients for carotid revascularisation, notably in the face of evidence that ipsilateral strokes on optimal medical therapy have declined significantly over time. [Table 2] summarises all the available guidelines published till date addressing the management of ACS.[9] The evidence supporting these recommendations is largely drawn from the randomised controlled trials (RCTs) explained below. The 2017 European Society of Vascular Surgery guidelines (ESVS) suggest that carotid endarterectomy (CEA) (class IIa recommendation, level of evidence B) or carotid stenting (class IIb, level of evidence B) should be considered for patients with ACS (60%–99%) at average surgical risk, provided the documented perioperative stroke/death rate is less than 3% and the patient's life expectancy exceeds 5 years.[10] This is in line with the other guidelines.[11],[12],[13],[14] Although all the guidelines suggest forming a multidisciplinary team for the management of these patients, the recommendations are not clear when it comes to carotid artery stenting (CAS) in both patients at average risk and high risk of complications of CEA.
Table 2: Summary of recommendations on the management of asymptomatic carotid stenosis

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   Carotid Revascularisation and the Evolution of Medical Management Top

The current evidence on management of ACS is based on several landmark trials. Three randomised controlled trials (RCTs) conducted in the 1990s investigated whether CEA could reduce the risk of stroke in patients with asymptomatic carotid stenosis, namely VA cooperative study group, Asymptomatic carotid atherosclerosis study (ACAS) and Asymptomatic carotid surgery trial 1 (ACST-1) trials.[3],[4],[15] [Table 3] These trials predominantly recruited participants with a stenosis ≥50%, although ACST-1 had no fixed minimum cut- off. All these trials reported significant benefit in favour of CEA. Although there are no direct RCTs evaluating the safety and efficacy of CAS over medical therapy, three RCTs compared the safety and efficacy of CAS with CEA, namely Stenting and angioplasty with protection in patients at high risk for endarterectomy (SAPPHIRE), Carotid revascularisation endarterectomy versus stenting trial (CREST-1) and Asymptomatic carotid trial 1 (ACT-1) trials.[5],[6],[16] [Table 4] None of the three studies showed a difference in event rates between CEA and CAS, providing evidence that carotid artery stenting with embolic protection is a reasonable alternative to endarterectomy in patients at average risk for CEA. However, the major limitation across all surgical trials in ACS is that the best medical management was not well established. Although aggressive medical treatment in ACAS trial constituted only aspirin[17], current concept of aggressive medical treatment includes lipid lowering therapy[18],[19] and optimal medical management of comorbidities like diabetes mellitus[20],[21], hypertension[22],[23], modification of life style including smoking cessation, moderation of alcohol intake, change in dietary habits and physical exercise[24],[25],[26],[27] [Table 5].
Table 3: Randomised controlled trials comparing CEA vs medical treatment alone in patients with asymptomatic carotid stenosis

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Table 4: Randomised controlled trials comparing CEA vs CAS in patients with asymptomatic carotid stenosis

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Table 5: Summary of optimal medical therapy[27]

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In 1995, ACAS trial reported 5-year risk of “ipsilateral” stroke of 11.0% (2.2% per annum) in patients receiving medical treatment with aspirin.[3] By 2004, the 5-year risk in ACST was reduced to 5.3% (1.1% per annum), whereas in years 6 to 10, the risk of “ipsilateral stroke” has decreased further to 3.6% (0.7% per annum) with modern medical treatment.[4] Evolution of medical treatment in the last two decades, especially with the introduction of intensive lipid lowering therapy has revolutionised the management of these patients.[18],[29],[30] A meta-analysis of the three most recently published studies on ACS patients receiving the best medical treatment showed an annual risk of 0.49% which is even less compared to the annual risk recorded in the 6-10 years results of ACST-1 trial.[31] These results signify that RCTs done so far have not included the best medical treatment. To support this notion, use of lipid lowering therapy and antihypertensive drugs increased significantly towards the end of study period in ACST-1 trial.[4] In the OxVasc study, the risk of ipsilateral stroke was only 0.34% per year in ACS patients receiving contemporary medical therapy.[32] Spence et al.[33] showed that intensive medical therapy based on treating arteries instead of treating risk factors was associated with lower risk of stroke and myocardial infarction (MI).

So had the medical treatment been optimal in the earlier RCTs, the results might have been different. There have been claims that advances in technology and increased experience may have led to reduction in risks following CAS and CEA which may increase the benefit of intervention in these patients. Naylor et al.[34] reanalysed the 5 and 10-years data from the ACAS and ACST trial with an assumption of 0% procedural risk. Modelling for a 0% procedural risk meant that more than 90% of these procedures were still unnecessary. On the contrary, in some cohort studies that included all three treatment groups, the results are conflicting [Table 6]. All these factors highlight the need for studies that can evaluate the efficacy of optimal medical management in comparison with CEA and CAS.
Table 6: Cohort studies comparing carotid revascularisation versus medical therapy in patients with asymptomatic carotid stenosis

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   Risk Stratification Top

Offering routine carotid revascularisation to every patient with asymptomatic carotid artery stenosis is no longer considered as the optimal management. Equally suboptimal, however, is the policy of offering only best medical treatment to these patients and not considering any of them for revascularisation. Some patients may not respond to medical management, and they may benefit from carotid revascularisation. It is essential to identify these subsets of patients who are at high risk of recurrence of events. Degree of stenosis alone may not be the best approach for identification of these patients. In the last few years, several methods have been proposed as reliable predictors for the identification of patients at high risk of stroke.[39] For some of these predictors, the evidence is adequate and robust, whereas for others it is weaker. Micro embolic signals detected on transcranial Doppler is a simple, convenient and cost-effective method that can help in risk stratification of these patients.[40]

[Table 7] summarises the clinical and imaging features that are associated with increased risk of stroke/TIA in ACS patients.[41]
Table 7: Clinical/imaging features associated with an increased risk of stroke in patients with ACS[41],[42]

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   Need for Future Trials Top

Although there are trials supporting revascularisation and emerging evidence towards best medical therapy, there is a lack of consensus as reflected in the guidelines addressing the management of these patients. Though guidelines recommend CEA in management of ACS patients, the data is based on trials that appear to be of only historical importance. However, intervention in every patient with ACS is not worthwhile. AHA recognises that only highly selected patients should undergo carotid revascularisation but have not defined what is highly selected population.[13] Risk stratification through various methods has been proposed for identifying the high risk population but there are no studies to suggest that selective screening will reduce fatal or disabling strokes. Finally, the recent decline in stroke rates with optimal medical management has not been evaluated in an RCT. It is difficult to frame guidelines for management of these patients with the existing controversies. With the recent publication of studies suggesting an association between ACS and cognitive decline the clinical decision-making is going to become worse.[43] Hence there is a need for trials which can clear the existing controversies. CREST-2,[44] ECST-2,[45] and ACST-2[46] are some of the ongoing RCTs in patients with ACS. [Table 8] provides characteristics of these ongoing trials. The results of these trials should answer the role of optimal medical treatment, indications for revascularisation (CEA/CAS) and risk stratification of patients with ACS. In the meantime, patients referred for revascularisation should have evidence of vulnerable plaque.
Table 8: Summarised characteristics of the on-going RCTs in patients with ACS

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   Conclusion Top

Asymptomatic carotid stenosis is a risk factor for stroke, myocardial infarction and mortality. Improvements in medical therapy have reduced the risk of cerebrovascular events possibly below a threshold where carotid revascularisation would still benefit the average risk patient. Although the results of the ongoing trials CREST-2,[44] ECST-2,[45] and ACST-2[46] awaited, all patients with ACS should receive optimal medical management for control of risk factors and comorbidities and patients with vulnerable plaque should be considered for revascularisation.

   References Top

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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]


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