Carotid and Cerebrovascular Disease

Background

Carotid artery stenosis is a leading cause of ischemic stroke, accounting for approximately 15–20% of all ischemic events worldwide (Sacco 2013)📄. Stroke remains the second most common cause of death globally and the primary cause of long-term disability in adults.

• Asymptomatic carotid stenosis (ACS): highly prevalent in aging populations, affecting ~5–10% of men >65 years [2]📄.
• Symptomatic carotid stenosis (SCS): presents with transient ischemic attack (TIA), minor stroke, or amaurosis fugax. The risk of stroke recurrence is highest in the first 2 weeks after a symptomatic event.
• Intervention: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) reduce stroke risk in selected patients.
• Modern evolution: improvements in medical therapy (statins, antiplatelets, antihypertensives) have lowered the absolute benefit of surgery in ACS (Abbott 2009)📄.

Atherosclerosis (most common)

• Progressive lipid accumulation and plaque formation, remaining the leading cause of cardiovascular disease (CVD) and stroke globally (Martin 2024).
• Hemodynamic stress at bifurcations promotes turbulence → plaque localization.

Non-atherosclerotic causes

• Carotid dissection (spontaneous or traumatic).
• Fibromuscular dysplasia (FMD): string-of-beads appearance, often in young women.
• Vasculitis: Takayasu arteritis, giant cell arteritis.
• Radiation-induced stenosis: after neck irradiation.

Risk factors

• Non-modifiable: age, male sex, genetics, and race/ethnicity (Repella 2025).
• Modifiable: smoking, hypertension, diabetes mellitus (DM), dyslipidemia (including elevated Lipoprotein(a) [Lp(a)]), obesity, and chronic kidney disease (CKD) (Das 2025)^,(Yang 2026).
• Systemic association: many patients with carotid disease also have 10PAD or coronary artery disease (CAD), a risk profile significantly influenced by the presence of DM (Das 2025).

Pathophysiology

1. Plaque development
2. * Endothelial injury → LDL infiltration → oxidation → foam cell formation.
3. * Plaque composition: lipid-rich necrotic core, fibrous cap, calcification.
4. Plaque vulnerability
5. * Thin fibrous cap, neovascularization, intraplaque hemorrhage.
6. * “Vulnerable plaques” are more prone to rupture and embolization.
7. Hemodynamic consequences
8. *Moderate stenosis (50–69%):** may be compensated.
9. *Severe stenosis (>70%):** turbulent flow, risk of thrombus formation, distal embolization, cerebral hypoperfusion.

Clinical Presentation

• Asymptomatic stenosis: discovered by bruit or imaging.
• transient ischemic attack (TIA): transient focal neurological deficit <24 h (usually <1 h).
• Stroke: persistent neurological deficit >24 h.
• Amaurosis fugax: transient monocular blindness, classic sign of ipsilateral carotid disease.

Stroke Risk by Category

• Symptomatic ≥70% stenosis: ~25% 2-year risk without treatment (NASCET 1991).
• Asymptomatic ≥60% stenosis: annual stroke risk ~0.5–1% with modern therapy (Halliday 2004)^,(Tessarek 2023).

Clinical assessment

• Full neurological exam (NIHSS, modified Rankin scale).
• Cardiovascular risk evaluation.
• Risk stratification: asymptomatic vs symptomatic is the key determinant of management.

Duplex Ultrasound

Duplex ultrasound is the first-line modality for screening and surveillance. Laboratory-validated velocity criteria should be used; the Society for Radiologists in Ultrasound (SRU) consensus suggests peak systolic velocity (PSV) ≥230 cm/s as a guide to ≥70% NASCET stenosis, though thresholds should be validated locally and interpreted in conjunction with end-diastolic velocity (EDV) and ICA/CCA ratios (Grant 2003). Stenosis should always be reported using the NASCET method to align with clinical trial and guideline thresholds.

Advantages: Non-invasive, repeatable, and inexpensive.

Limitations: Operator-dependent interpretation and artifacts from heavy calcification.

CT Angiography

• Gold standard for anatomic assessment.
• Defines stenosis, plaque morphology (calcified vs soft vs mixed), and intracranial vessels.
• Provides surgical/endovascular planning.

MR Angiography

• Magnetic resonance angiography (MRA) is a Class 1 recommendation for the anatomic assessment of lower extremity peripheral artery disease (PAD) when revascularization is planned (Gornik 2024).
• It serves as an alternative when computed tomography angiography (CTA) is contraindicated due to renal dysfunction or iodinated contrast allergy (Gornik 2024).
• Contrast-enhanced magnetic resonance angiography (CE-MRA) provides high-resolution images for both PAD and aortic disease, including aneurysms and dissections (Isselbacher 2022)^,(Gornik 2024).
• MRA is particularly useful for serial surveillance of aortic disease to minimize ionizing radiation exposure (Isselbacher 2022).
• For patients with severe chronic kidney disease (CKD), non-contrast MRA techniques may be utilized to avoid the risk of nephrogenic systemic fibrosis (NSF) associated with certain gadolinium-based contrast agents (Gornik 2024).

Digital Subtraction Angiography

• Historically reference standard.
• Now reserved for intervention.
• Risk: 0.5–1% stroke.

Plaque Imaging

In asymptomatic carotid stenosis (ACS), high-risk plaque features identify patients at elevated ipsilateral stroke risk and may support consideration of revascularization in otherwise borderline cases. These features include MRI-detected intraplaque hemorrhage, plaque ulceration, echolucency on ultrasound, and transcranial Doppler (TCD) microembolic signals (Tessarek 2023).

Optimal Medical Therapy

Antiplatelet therapy: For carotid endarterectomy (CEA), single antiplatelet therapy (aspirin 75–325 mg daily) should be administered preoperatively and continued indefinitely. For carotid artery stenting (CAS) and transcarotid artery revascularization (TCAR), dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is recommended for at least 1 month (often extended to 3 months), followed by single antiplatelet therapy (Tessarek 2023). Given the variability in clopidogrel metabolism, CYP2C19 genotype-guided therapy may be considered to identify poor metabolizers who may require alternative antiplatelet strategies (Lee 2022). In patients with high-risk transient ischemic attack (TIA) or minor stroke, short-term DAPT reduces early stroke recurrence (CHANCE, POINT trials) (Johnston 2018)📄^,(Wang 2013).

Lipid management: High-intensity statin therapy is indicated for all patients with atherosclerotic carotid disease. The SPARCL trial demonstrated that intensive statin therapy reduces stroke recurrence (Amarenco 2006)📄. Consider adding ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors if low-density lipoprotein (LDL) cholesterol remains above target (Tessarek 2023).

Blood pressure control: Target blood pressure <130/80 mmHg in most patients with prior stroke or TIA if tolerated (Kleindorfer 2021)📄.

Diabetes management: Individualized glycemic control (often hemoglobin A1c (HbA1c) <7%) with comprehensive cardiovascular risk reduction (Kleindorfer 2021)📄.

Lifestyle modifications: Smoking cessation, weight management, Mediterranean-style diet, and regular physical activity are essential components of secondary prevention (Kleindorfer 2021)📄. Despite the proven benefits of optimal medical therapy (OMT), adherence remains suboptimal in many patients undergoing carotid interventions; however, consistent OMT is associated with significantly smaller areas of cerebral infarction in the event of a subsequent stroke (Teter 2024).

Carotid Endarterectomy

Carotid endarterectomy (CEA) is the gold standard surgical treatment for symptomatic carotid stenosis. Landmark trials established its efficacy: North American Symptomatic Carotid Endarterectomy Trial (NASCET) (1991) demonstrated that CEA reduced stroke risk in patients with symptomatic stenosis ≥70% (NASCET 1991), and European Carotid Surgery Trial (ECST) (1998) confirmed this benefit (Rothwell 1998). Beyond clinical efficacy, CEA remains more cost-effective than carotid artery stenting (CAS) in most clinical scenarios (Akkara 2025). In asymptomatic patients, Asymptomatic Carotid Atherosclerosis Study (ACAS) (1995) and Asymptomatic Carotid Surgery Trial (ACST) (2004) showed a small benefit for stenosis ≥60%, though this advantage is less pronounced with modern medical therapy.

CEA is recommended for symptomatic stenosis of 50–99% when performed within 14 days of transient ischemic attack (TIA) or non-disabling stroke, provided the perioperative stroke or death risk is <6% [@society2021; @esvs2023]. In asymptomatic carotid stenosis (ACS), routine CEA is not indicated. However, it may be considered in highly selected patients with ≥60% stenosis who have a life expectancy >3–5 years, low perioperative risk (<3%), and high-risk imaging features [@society2021; @esvs2023].

Acceptable perioperative complication rates are crucial: <6% stroke or death for symptomatic patients and <3% for asymptomatic patients (Abu 2021).

Carotid Artery Stenting

• Minimally invasive alternative to carotid endarterectomy (CEA).
• CREST (2010): 7Carotid vs 7Carotid → no difference in long-term stroke/myocardial infarction (MI)/death, but 7Carotid had higher peri-procedural stroke, lower MI (Brott 2010).
• ICSS (2010): higher peri-procedural stroke with 7Carotid.
• Indications: high surgical risk, restenosis after 7Carotid, radiation-induced stenosis.
• Embolic protection devices (EPD) are strongly recommended for transfemoral CAS.
• Transcarotid Artery Revascularization (TCAR): A hybrid approach utilizing direct carotid access and dynamic flow reversal for embolic protection. Systematic reviews support the role of TCAR in managing symptomatic carotid stenosis (Liapis 2026). Long-term data from a decade of community practice demonstrate that TCAR provides durable outcomes and a favorable safety profile (Kenny 2025).

Transcarotid Artery Revascularization

• Hybrid technique: surgical exposure of common carotid + stent via direct puncture + flow reversal neuroprotection.
• ROADSTER trial (2019): low peri-procedural stroke rates (Malas 2019)📄.
• Emerging alternative in high-risk patients.

Follow-up

Post-procedure surveillance: Duplex ultrasound surveillance should be tailored to individual risk factors, including early residual stenosis, periprocedural complications, and contralateral severe disease. A common surveillance schedule includes imaging at 1, 6, and 12 months, followed by annual examinations if findings remain stable (Tessarek 2023).

Medical therapy: Lifelong secondary prevention with optimal medical therapy is mandatory regardless of revascularization, including antiplatelet agents, statins, blood pressure control, and lifestyle modifications (Tessarek 2023)^,(Kleindorfer 2021)📄.

Restenosis: Patch closure during carotid endarterectomy (CEA) reduces restenosis rates compared with primary closure. Clinically significant restenosis after CEA or carotid artery stenting (CAS) is uncommon, occurring in approximately 10–15% after CEA and 5–10% after CAS. Symptomatic or high-grade (≥70%) restenosis, including in-stent restenosis (ISR), should be managed with reintervention (repeat CEA, CAS, TCAR, or endovascular treatment for ISR) in experienced centers (Tessarek 2023).

Tables

Table 7.1. Indications for Carotid Revascularization (Guidelines)

Table 7.2. CEA vs CAS – Comparative Outcomes

Asymptomatic carotid stenosis (ACS): contemporary selection for intervention vs best medical therapy (BMT)

Best medical therapy (BMT) is the first-line approach for most patients with asymptomatic carotid stenosis (ACS) in the contemporary era. Intervention may be considered for patients with ≥60% ACS only when perioperative risk is <3%, life expectancy exceeds 3–5 years, and one or more high-risk features are present. These high-risk features include rapid stenosis progression, ipsilateral silent cerebral infarcts, intraplaque hemorrhage or ulceration on imaging, echolucent plaque characteristics, microembolic signals on transcranial Doppler (TCD), or contralateral internal carotid artery (ICA) occlusion.

For procedure selection in patients deemed appropriate for revascularization, carotid endarterectomy (CEA) is preferred in average-risk patients, while carotid artery stenting (CAS) or TCAR may be favored when anatomic considerations or surgical risk factors support an endovascular approach. The ACST-2 randomized controlled trial demonstrated that CEA and CAS provide similar medium-term outcomes in asymptomatic patients selected for revascularization. The ongoing CREST-2 trial is evaluating BMT alone versus revascularization plus BMT in patients with asymptomatic carotid stenosis.

Modern CEA vs CAS evidence synthesis and patient selection (ACT-1/ACST-2; age/anatomy modifiers)

Recent evidence has refined the comparative outcomes of carotid endarterectomy (CEA) versus carotid artery stenting (CAS). In asymptomatic patients, the ACST-2 trial demonstrated similar medium-term non-procedural stroke rates for CEA versus CAS, with acceptably low rates of procedural disabling stroke or death for both approaches. In mixed symptomatic and asymptomatic cohorts, the CREST trial showed similar long-term composite outcomes, though with important differences in perioperative events: CAS was associated with higher periprocedural stroke rates, while CEA had higher myocardial infarction rates. Patient age significantly modifies these outcomes, with older patients generally achieving better results with CEA compared to CAS.

These findings inform contemporary patient selection for revascularization strategy. CEA remains preferred for most average-risk patients, particularly those of advanced age. CAS or TCAR may be favored in patients with high surgical risk, unfavorable neck anatomy for surgery, prior neck irradiation, or recurrent stenosis after previous CEA.

Timing of carotid intervention after TIA/minor stroke and after thrombolysis

The timing of carotid revascularization after neurological events is critical to balancing stroke prevention against procedural risk. For symptomatic stenosis of 50–99%, carotid endarterectomy (CEA) should be performed as soon as feasible within 14 days of the index transient ischemic attack (TIA) or non-disabling stroke, with an ideal window of within 7 days. In experienced centers, urgent CEA (<48–72 hours) may be considered for patients with crescendo TIA or neurologically unstable symptoms.

Special considerations apply after acute stroke treatment or in the setting of large cerebral infarction. Following intravenous thrombolysis or in cases of large infarction with hemorrhagic transformation, carotid intervention should be deferred until the patient is neurologically and radiographically stable. While carotid artery stenting (CAS) timing follows similar principles, hyperacute CAS is generally avoided due to elevated periprocedural stroke risk in this setting.

Imaging criteria: stenosis grading standards and plaque vulnerability features

Standardized stenosis grading is essential for consistent clinical decision-making and comparison with clinical trial evidence. Carotid stenosis should be reported using the NASCET (North American Symptomatic Carotid Endarterectomy Trial) method. If alternative grading methods are employed, they should be explicitly specified, and direct cross-conversion between methods should be avoided due to inherent measurement differences.

Duplex ultrasound velocity thresholds should follow laboratory-specific validation protocols. The Society for Radiologists in Ultrasound (SRU) consensus suggests peak systolic velocity (PSV) ≥230 cm/s as a guide for identifying ≥70% NASCET stenosis, though local validation with correlation to other imaging modalities is recommended.

High-risk plaque features have emerged as important modifiers of stroke risk in asymptomatic carotid stenosis. These features include intraplaque hemorrhage (IPH) on MRI, plaque ulceration, echolucent plaque characteristics on ultrasound, microembolic signals on transcranial Doppler (TCD), rapid stenosis progression, and ipsilateral silent cerebral infarcts on imaging. The presence of these features increases stroke risk and may influence decision-making regarding revascularization in otherwise borderline cases.

Peri-procedural antithrombotic therapy for CEA/CAS/TCAR

Optimal periprocedural antithrombotic management is critical to preventing both thrombotic and hemorrhagic complications. For carotid endarterectomy (CEA), single antiplatelet therapy with aspirin (75–325 mg daily) should be administered preoperatively and continued indefinitely. For carotid artery stenting (CAS) and transcarotid artery revascularization (TCAR), dual antiplatelet therapy with aspirin plus clopidogrel is recommended for at least 1 month, with many centers extending this to 3 months, followed by single antiplatelet therapy thereafter.

High-intensity statin therapy should be initiated or optimized before the procedure in all patients. Patients on therapeutic anticoagulation require individualized management based on the specific procedure planned, indication for anticoagulation, and institutional protocols, with consideration of bridging strategies when appropriate.

Surveillance and restenosis management (including in-stent restenosis)

Surgical technique influences long-term outcomes after carotid endarterectomy (CEA). Patch closure reduces restenosis rates compared with primary arteriotomy closure and is widely employed in contemporary practice.

Post-procedure surveillance with duplex ultrasound should be tailored to individual risk profiles, with more intensive monitoring for high-risk subsets including patients with periprocedural complications, residual stenosis, or contralateral severe disease. Surveillance protocols typically include imaging at 1, 6, and 12 months, followed by annual examinations if stable.

In-stent restenosis (ISR) after carotid artery stenting (CAS) is diagnosed using duplex ultrasound criteria similar to those for native vessel stenosis, with PSV ≥230 cm/s generally corresponding to ≥70% stenosis, though stent type may influence velocity measurements. Reintervention is indicated for symptomatic ISR or high-grade (≥70%) asymptomatic ISR in selected patients. Treatment options include repeat angioplasty, drug-coated balloon angioplasty, or surgical revision, with choice dependent on anatomy, patient factors, and institutional expertise.

Role and Indications of TCAR Relative to CAS and CEA

Transcarotid artery revascularization (TCAR) represents a hybrid approach that combines direct surgical carotid access with endovascular stent placement. TCAR may be considered in patients at elevated risk for transfemoral carotid artery stenting (CAS) due to unfavorable aortic arch anatomy, severe arch tortuosity, hostile neck anatomy from prior surgery or radiation, or recurrent stenosis. Contemporary registry data suggest that TCAR achieves perioperative outcomes comparable to both carotid endarterectomy (CEA) and transfemoral CAS.

TCAR employs flow reversal through extracorporeal circulation as a neuroprotection strategy during stent deployment, reducing the risk of cerebral embolization. As with standard CAS, dual antiplatelet therapy with aspirin and clopidogrel is required for at least 1 month (often 3 months) following TCAR, followed by indefinite single antiplatelet therapy.

Evidence-based carotid revascularization overview

The optimal approach to carotid revascularization—carotid artery stenting (CAS) versus carotid endarterectomy (CEA)—has been extensively studied. The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar long-term composite outcomes for stroke, myocardial infarction, and death with both techniques (Brott 2010).

However, CREST identified important age-related differences in procedural risk. CAS was associated with lower perioperative risk in younger patients (< 70 years), while CEA showed superior outcomes in older patients. The periprocedural hazard profiles also differed: CAS carried higher stroke risk, while CEA was associated with higher myocardial infarction risk.

For symptomatic carotid stenosis ≥ 50%, both techniques are effective when performed by experienced operators. In asymptomatic disease, indications for intervention continue to evolve. Optimal medical therapy has improved substantially since foundational trials (ACAS, ACST) were conducted, narrowing the benefit of prophylactic intervention. Current practice emphasizes patient selection based on stenosis severity (≥ 60–70%), life expectancy, surgical risk, and institutional expertise.