Optimal Stroke Risk Management in Carotid Atherosclerotic Disease: A Patient-Centered Multidisciplinary Approach

A multispecialty Consensus statement recently released by the European Society of Cardiology (ESC) Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Disease covers several key aspects of the diagnosis and management of carotid artery stenosis. ¹ The expert panel included opinion leaders from different specialties that deliver primary and secondary care for patients with asymptomatic carotid stenosis (AsxCS) and carotid-related strokes. ¹ This multispecialty participation minimized “surgical” versus “endovascular” versus “exclusively pharmacological” bias by defining a common knowledge base and delivering a balanced Consensus.

Several issues are now clear in the management of patients with AsxCS and symptomatic carotid stenosis (SxCS), such as:

i) Not all AsxCS patients carry the same stroke risk. Consequently, their management should be individualized.

ii) SxCS patients presenting with carotid-related strokes, or radiologic signs of cerebral injury, may benefit from individualized management.

iii) Procedural results and patient adherence may differ between randomized controlled trials (RCTs), registries, and routine clinical settings.

This Editorial considers these three issues.

Stratification of Stroke Risk and Individualized Management of AsxCS Patients

Once AsxCS is detected, intensive risk factor modification and best medical treatment (BMT) should be rigorously implemented in all patients. ² BMT is the cornerstone of the management of AsxCS and consists of various components. These include lifestyle changes (e.g., smoking cessation, weight loss, minimal alcohol consumption, moderate exercise, and adopting a healthy diet) and pharmacological measures, for example, blood pressure and diabetes control, antiplatelet agents, and lipid-lowering treatment with statins/ezetimibe and possibly with proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors. ²

Risk prediction scores and stratification algorithms are necessary to calculate the future stroke risk of each AsxCS patient. ³ The largest natural history study on patients with 50%–99% AsxCS, the Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS), provided evidence that not all AsxCS patients carry the same stroke risk, and that a combination of features (namely, carotid plaque type, gray scale median, carotid plaque area, juxtaluminal black area without a visible echogenic cup, discrete white areas in an echolucent part of the carotid plaque, silent embolic infarcts on brain CT scans, and/or a combination of these features) can stratify patients into various categories regarding their stroke risk.^4,5 The best stroke risk stratification was provided by a combination of plaque texture features (e.g., juxtaluminal black area of ≥8 mm² without a visible echogenic cap and discrete white areas in hypoechoic plaques) with percentage of AsxCS stenosis severity, as well as a history of contralateral transient ischemic attack (TIA) or stroke.^4,5

The 2017 European Society of Cardiology/European Society for Vascular Surgery guidelines and the 2023 European Society for Vascular Surgery guidelines for the management of patients with AsxCS listed specific clinical/imaging features associated with increased risk of late ipsilateral stroke in patients with 50%–99% AsxCS.^6,7 These include silent ipsilateral infarction on brain CT/MRI scans, spontaneous embolization on transcranial Doppler monitoring, stenosis progression, a large juxtaluminal black area on computerized plaque analysis, intraplaque hemorrhage on MRI, impaired cerebrovascular reserve, plaque echolucency on duplex ultrasound, and history of contralateral TIA/stroke.^6,7 These and other features of increased carotid-related risk of stroke are discussed in more detail in the Consensus document. ¹ According to the 2023 ESVS Guidelines, ⁶ for AsxCS patients with clinical/imaging features associated with an increased risk of future stroke, carotid endarterectomy (CEA) should (Class IIa; Level of Evidence: B) and carotid artery stenting (CAS) may be considered (Class IIb; Level of Evidence: B), provided the patient’s life expectancy exceeds 5 years and 30-day stroke/death rates associated with the intervention are ≤3%. There is evidence suggesting that the management of AsxCS patients should be individualized, taking into consideration individual patient needs and characteristics, including life expectancy and comorbidities, ethnic, cultural and social characteristics, as well as personal preferences. ⁸ Stratification of future stroke risk and a patient-centered approach taking into consideration local expertise should therefore guide the management of AsxCS patients, as highlighted in the Consensus document, along with the evidence from the emerging RCTs and registries for the safety and efficacy of novel CAS technologies, such as improved intraprocedural cerebral protection (e.g., flow reversal, “mesh” stents) and post-procedural prevention of plaque-related embolism with “mesh” stents.^1,9

Individualized Treatment for SxCS Patients

Besides AsxCS individuals, ⁸ the management of patients with a recent cerebrovascular event (TIA/stroke) should also be individualized, albeit to a lesser extent. Both the European ⁵ and the American^7,10 guidelines on the management of carotid patients clearly indicate that although CEA should be the treatment-of-choice for recent SxCS patients, CAS should be considered as an alternative, particularly in specific patient subgroups (e.g., those with high carotid bifurcation, tracheal stoma, scarred neck from previous radiotherapy, and other conditions that place patients at “high risk” with CEA). With several studies already published, and several more on-going, novel carotid stent technologies and improved intraprocedural cerebral protection may increase (“2^nd generation”) CAS applicability to SxCS. ¹

Besides CAS and CEA, a novel hybrid technique has emerged for the management of carotid patients, namely, transcarotid artery revascularization (TCAR). Indirect comparisons suggest that TCAR may be associated with better outcomes compared with CAS and with equal stroke/death rates with CEA.^11,12 However, TCAR has never been compared with either CAS or CEA within an RCT. Other drawbacks are a 1^st generation (single-layer) stent in TCAR today, the relatively high cost, and the lack of wide availability of TCAR equipment. These limitations may be addressed in the near future.

Procedural Results and Patient Adherence in RCTs and in Clinical Settings

The Consensus document underscores that while RCTs are essential for comparing the efficacy of CAS versus CEA, certain drawbacks are relevant to everyday clinical practice. ¹ Such drawbacks include patient selection bias, superior (or inferior) outcomes of surgeons/interventionalists participating in RCTs compared with usual clinical practice, and lack of generalizability of the results of RCTs to everyday clinical settings.^1,13 Although RCT conclusions are valid for specific patient subgroups (i.e., those included in the RCTs), they are often applied to a broader population. ¹ In contrast to RCTs, registries may report worse (or better) procedural outcomes in "real-life" settings. Therefore, RCTs may often not reflect reality and may be misleading. ¹³ Therefore, when making treatment decisions, the existing evidence should be considered in the context of local expertise and patient preferences. ¹

Besides procedural risk, due to the strict management and rigorous follow-up of patients within RCTs, patient adherence is superior compared with everyday clinical practice. ¹³ Expecting that all patients will be constantly and fully adherent with the advice provided by their vascular surgeons/physicians is unrealistic. Drug intolerance and discontinuation rates for some agents (e.g., statins)^14–16 may be high in everyday clinical practice, thus resulting in inadequate and suboptimal stroke prevention measures. Risks with other drugs (e.g., potential bleeding risk with antiplatelet agents) need to be weighed against patient benefit. ¹ These issues are also covered in the Consensus document ¹ and highlight the importance of patient-centered care.

In conclusion, the recent Consensus statement defines contemporary knowledge and provides a balanced discussion of the current issues concerning the management of both AsxCS and SxCS patients. ¹ It recognizes the fundamental role of lifestyle modification and pharmacological therapy for AsxCS and SxCS patients and provides guidance for clinicians who aim to achieve patient-centered, evidence-based care.