- ACRONYMS AND DEFINITIONS
- ACC - American College of Cardiology
- AHA - American Heart Association
- ASA - American Stroke Association
- Amaurosis Fugax - a type of TIA where vision is temporarily lost in one eye
- CAS - Carotid artery stenting
- CEA - Carotid endarterectomy (procedure where atherosclerotic plaque is surgically removed)
- CTA - CT Angiography (CT scan with arterial contrast)
- MRA - MR Angiography (MRI scan with arterial contrast)
- RCT - Randomized controlled trial
- TIA - Transient Ischemic Attack (syndrome where a person experiences stroke symptoms that resolve in < 24 hours)
- USPSTF - United States Preventive Services Task Force
- PHYSIOLOGY
- There are two carotid arteries on either side of the neck. The common carotid artery bifurcates into the internal and external carotid artery.
- The internal carotid artery is one of the main blood supplies to the brain
- Carotid artery stenosis is a condition where one or both of the carotid arteries in the neck are narrowed due to atherosclerotic plaque
- A common place for the stenosis to occur is at the bifurcation of the common carotid artery. The bifurcation is the place where the common carotid artery bifurcates into the external and internal carotid arteries.
- Carotid stenosis increases a person's risk for stroke
- Carotid stenosis is typically diagnosed with a carotid ultrasound
- RISK FACTORS
- Overview
- Risk factors for carotid stenosis are the same as those for other diseases that are caused by atherosclerosis (e.g. coronary artery disease, peripheral artery disease, cerebrovascular disease)
- Risk factors for carotid stenosis:
- Diabetes
- High blood pressure
- High cholesterol
- Family history of early-onset CAD (defined as CAD in a first-degree male relative < 55 years old, or CAD in a first-degree female relative < 65 years old)
- Smoking
- Physical inactivity
- Obesity
- Male sex
- History of stroke or peripheral artery disease
- Age (men > 45 years old, women > 55 years)
- STROKE RISK
- Stroke risk
- The risk of stroke with carotid stenosis depends on the degree of stenosis and whether the stenosis is asymptomatic or symptomatic. Asymptomatic carotid stenosis is defined as stenosis in a person who has never had a stroke or TIA on the affected side. Symptomatic stenosis is stenosis in a person who has had a stroke or TIA on the affected side. The degree of stenosis is typically quantified with a carotid ultrasound.
- The risk of stroke for symptomatic patients has been evaluated in a number of studies. The risk for asymptomatic patients is not well defined. The first table below gives the annual stroke risk for different degrees of stenosis in patients who were taking daily aspirin. The second table shows the risk of stroke in a cohort of asymptomatic patients diagnosed with severe stenosis between 2008 and 2012. The use of antiplatelet therapy in these patients was not assessed.
| Symptomatic carotid stenosis | |
|---|---|
| Degree of stenosis | Annual stroke rate |
| ≥ 70% | 13% |
| 50 - 69% | 4.4% |
| ≤ 50% | 3.74% |
| Asymptomatic carotid stenosis | |
| Degree of stenosis | Annual stroke rate |
| ≥ 60% | 2 - 3% |
| Asymptomatic severe (70 - 99%) carotid stenosis | |
|---|---|
| Outcome | Stroke risk |
| Annual stroke risk | 0.9% |
| Estimated 5-year risk | 4.7% |
- SCREENING
- Primary prevention
- USPSTF
- In 2014, the USPSTF recommended against screening for asymptomatic carotid stenosis in the general population
- AHA/ACC/ASA
- The AHA, ACC, and ASA all recommended against screening for asymptomatic carotid stenosis in the general population
- Secondary prevention
- Because carotid stenosis is a potentially treatable source of stroke, all patients who have experienced an ischemic stroke or TIA that is thought to be of thromboembolic origin should be screened for carotid stenosis
- DIAGNOSIS
- Symptoms
- The primary symptom of carotid stenosis is stroke or transient ischemic attack (TIA)
- One type of TIA that is often associated with carotid stenosis is a syndrome referred to as "amaurosis fugax." Amaurosis fugax has been described as a shade being pulled down or up over the visual field in one eye. Carotid stenosis is the most common cause of amaurosis fugax.
- Physical exam
- Some patients with carotid stenosis will have a finding on physical exam called a carotid bruit
- A carotid bruit is a flow murmur heard over the carotid artery during systole
- Carotid bruits have a low sensitivity and specificity for significant carotid stenosis. Over a third of patients with high-grade carotid stenosis (70 - 99%) will not have a carotid bruit on physical exam. [2]
- Ultrasound
- Most patients are diagnosed with carotid stenosis when they have a stroke or TIA and a carotid ultrasound is performed
- When angiography is used as the reference standard, ultrasound has a sensitivity of 85% and a specificity of 90% for detecting significant stenosis (≥ 70%) [1]
- TREATMENT
- Overview
- There are 3 ways to treat carotid stenosis:
- Medical therapy - antiplatelet therapy, statins, stroke risk factor management
- Carotid endarterectomy (CEA) - surgical removal of the occluding atherosclerotic plaque
- Carotid artery stenting (CAS) - stenting of the carotid occlusion
- Asymptomatic patients
- Most carotid endarterectomies in the U.S. are performed on asymptomatic patients. A 5-year study (N=513) published in 2022 found that optimal medical therapy was noninferior to CEA or CAS for a composite of stroke or death in patients with asymptomatic stenosis ≥ 70%. [PMID 36115360]. However, the trial was plagued by poor enrollment and ended up being underpowered to detect a meaningful difference. A larger trial of similar design (www.crest2trial.org) is currently underway and should provide some much-needed guidance on treating these patients. Recommendations from the AHA are provided below.
- AHA 2011 recommendations for all patients with asymptomatic carotid stenosis
- Antiplatelet therapy - Daily aspirin 75 - 325 mg. Clopidogrel and Aggrenox® (aspirin + dipyridamole) are acceptable alternatives.
- Statin therapy - target LDL < 100 mg/dl
- Blood pressure control - target blood pressure < 140/90
- AHA 2011 recommendations for patients with asymptomatic carotid stenosis that is ≥ 70%
- CEA or CAS is "reasonable" in patients at low risk for surgical complications
- No recommendation is made in favor of either procedure [1]
- Symptomatic patients
- Treatment of carotid stenosis in symptomatic patients depends on the degree of stenosis
- All patients with symptomatic carotid stenosis should receive medical therapy. Patients with stenosis ≥ 70% should have CEA or CES if they are good surgical candidates.
- The table below compares the risks of surgery vs medical therapy stratified by the degree of stenosis
- Carotid endarterectomy (CEA) vs medical therapy
- Several large trials have compared CEA to medical therapy for significant outcomes in symptomatic patients
- Pooled results from three of the most well-known trials are presented below
- NOTE: These trials were performed before the widespread use of potent statins and other medications that affect stroke risk factors. It is unclear what the difference in outcomes would be with current therapy.
| Degree of stenosis | Absolute risk reduction in the primary outcome✝ after 5 years (CEA minus medical therapy) |
|---|---|
| 90 - 99% | 32.4% |
| 80 - 89% | 17.7% |
| 70 - 79% | 15.8% |
| 60 - 69% | 5.9% (nonsignificant) |
| 50 - 59% | 4% (nonsignificant) |
| 30 - 49% | 3.2% (nonsignificant) |
| < 30% | -2.2% (worse outcome for CEA) (nonsignificant) |
| Near-occlusion (defined as 95% stenosis) |
-1.7% (worse outcome for CEA) (nonsignificant) See occlusion below |
- AHA 2011 recommendations for all patients with symptomatic carotid stenosis
- Antiplatelet therapy - Daily aspirin 75 - 325 mg. Clopidogrel and Aggrenox® (aspirin + dipyridamole) are acceptable alternatives.
- Statin therapy - target LDL < 100 mg/dl
- Blood pressure control - target blood pressure < 140/90
- AHA 2011 recommendations for symptomatic carotid stenosis that is ≥ 70% on ultrasound or > 50% on angiography
- CEA or CAS in appropriate patients who have a perioperative mortality risk < 6%
- No recommendation is made in favor of either procedure [1]
- TREATMENT | Studies
- Overview
- Four large trials detailed below have compared CEA to CAS in the treatment of carotid stenosis. The trials vary by whether they enrolled asymptomatic patients (ACT I, ACST-2), symptomatic patients (ICSS), or both (CREST).
- The ACT I trial enrolled 1453 patients with asymptomatic carotid stenosis
Main inclusion criteria
- Age ≤ 79 years
- Asymptomatic carotid stenosis defined as having been free, in the ipsilateral hemisphere, from stroke, TIA, and amaurosis fugax for 180 days before enrollment
- Stenosis of 70 - 99% in the absence of substantial (> 60%) contralateral stenosis
Main exclusion criteria
- High risk for operative complications
- Intracranial hemorrhage or hemorrhagic stroke within 1 year
Baseline characteristics
- Average age 68 years
- History of stroke ∼ 5.7%
- History of TIA - 7%
- Average % stenosis - 74%
- Average lesion length - 18.5 mm
- History of CAD - 52%
Randomized treatment groups
- Group 1 (1089 patients) - CAS
- Group 2 (364 patients) - CEA
- All patients received aspirin 325 mg once daily starting 3 days before the procedure and continued indefinitely
- Patients who had CAS received clopidogrel 75 mg once daily starting 3 days before the procedure and for 30 days thereafter
Primary outcome: Composite of death, stroke (ipsilateral or contralateral, major or minor) or myocardial infarction during the
30 days after the procedure or ipsilateral stroke during the 365 days after the procedure
Results
| Duration: 365 days | |||
| Outcome | CAS | CEA | Comparisons |
|---|---|---|---|
| Primary outcome | 3.8% | 3.4% | p=0.69 |
| Periprocedural stroke (within 30 days) | 2.8% | 1.4% | p=0.23 |
| Periprocedural heart attack (within 30 days) | 0.5% | 0.9% | p=0.41 |
| Overall mortality (estimated 5-year) | 12.9% | 10.6% | p=0.21 |
| Any stroke (estimated 5-year) | 6.9% | 5.3% | p=0.44 |
|
|||
Findings: In this trial involving asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications, stenting was noninferior
to endarterectomy with regard to the rate of the primary composite end point at 1 year. In analyses that included up to 5 years of follow-up, there were no significant differences between the
study groups in the rates of non-procedure-related stroke, all stroke, and survival.
- STUDY
- Design: Randomized, controlled trial (N=3625 | length = 5 years) in asymptomatic patients with severe (> 60%) unilateral or bilateral carotid stenosis
- Treatment: CAS vs CEA
- Primary outcome: Procedural stroke and MI (within 30 days after the intervention) and non-procedural stroke
- Results:
- Primary outcome (procedural stroke): CAS - 3.6%, CEA - 2.4% (p=0.06)
- Primary outcome (procedural MI): CAS - 0.3%, CEA - 0.7% (p=0.15)
- Primary outcome (non-procedural stroke): CAS - 5.3%, CEA - 4.5% (p=0.33)
- Findings: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable.
- The ICSS trial enrolled 1713 patients with symptomatic carotid stenosis
Main inclusion criteria
- Symptomatic carotid artery stenosis with ≥ 50% stenosis of the carotid artery
- Eligible for CEA and CAS
Main exclusion criteria
- History of major stroke
Baseline characteristics
- Average age 70 years
- ≥ 70% stenosis - 90% of subjects
- Most recent event: Ipsilateral ischemic stroke - 45% | Ipsilateral TIA - 33% | Amaurosis fugax - 17%
Randomized treatment groups
- Group 1 (855 patients) - CAS
- Group 2 (858 patients) - CEA
Primary outcome: Fatal or disabling stroke in any territory after randomisation to the end of follow-up
Results
| Duration: Median of 4.2 years | |||
| Outcome | CAS | CEA | Comparisons |
|---|---|---|---|
| Primary outcome | 6.4% | 6.5% | HR 1.06, 95%CI [0.72 – 1.57], p=0.77 |
| Any stroke | 15.2% | 9.4% | HR 1.71, 95%CI [1.28 – 2.30], p<0.001 |
| Overall mortality | 17.4% | 17.2% | HR 1.17, 95%CI [0.92 – 1.48], p=0.19 |
Findings: Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis
- The CREST trial enrolled 2522 patients with symptomatic or asymptomatic carotid stenosis
Main inclusion criteria
- Symptomatic patients - stroke or TIA within 180 days of study entry, stenosis ≥ 70% (ultrasound, CTA, MRA) or ≥ 50% on angiography
- Asymptomatic patients - carotid stenosis ≥ 60% on angiography, ≥ 70% on ultrasound, ≥ 80% on CTA or MRA
Main exclusion criteria
- Previous severe stroke
- A fib
- MI within 30 days
Baseline characteristics
- Average age 69 years
- Asymptomatic carotid stenosis - 47%
- Severe stenosis (≥ 70%) - 86%
Randomized treatment groups
- Group 1 (1262 patients) - CAS
- Group 2 (1240 patients) - CEA
Primary outcome: Composite of stroke, heart attack, periprocedural all-cause mortality, and same-sided stroke within
4 years of randomization (estimated with Kaplan-Meier curve)
Results
| Duration: Median of 2.5 years | |||
| Outcome | CAS | CEA | Comparisons |
|---|---|---|---|
| Primary outcome | 7.2% | 6.8% | HR 1.11, 95%CI [0.81 - 1.51], p=0.51 |
| Periprocedural stroke (within 30 days) | 4.1% | 2.3% | HR 1.79, 95%CI [1.14 - 2.82], p=0.01 |
| Periprocedural heart attack (within 30 days) | 1.1% | 2.3% | HR 0.50, 95%CI [0.26 - 0.94], p=0.03 |
| Overall mortality | 11.3% | 12.6% | HR 1.12, 95%CI [0.83 - 1.51], p=0.45 |
|
|||
Findings: Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ
significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with
stenting and a higher risk of myocardial infarction with endarterectomy.
- A follow-up to the CREST trial was published in 2016. It tracked 2502 patients from the original trial for up to 10 years.
| Duration: Median 7.4 years | |||
| Outcome (10-year estimated) | CAS | CEA | Comparisons |
|---|---|---|---|
| Primary outcome | 11.8% | 9.9% | HR 1.10, 95%CI [0.83 - 1.44], p=0.51 |
| Stroke or periprocedural death | 11% | 7.9% | HR 1.37, 95%CI [1.01 - 1.86], p=0.04 |
| Any stroke | 10.8% | 7.9% | HR 1.33, 95%CI [0.98 - 1.80], p=0.07 |
| Postprocedural ipsilateral stroke | 6.9% | 5.6% | HR 0.99, 95%CI [0.64 - 1.52] |
|
|||
Findings: Over 10 years of follow-up, we did not find a significant difference between patients who underwent stenting and those who underwent endarterectomy
with respect to the risk of periprocedural stroke, myocardial infarction, or death and subsequent ipsilateral stroke. The rate of postprocedural ipsilateral stroke also did not differ between groups.
- AHA recommendations
- The AHA 2011 carotid stenosis recommendations do not make definitive recommendation one way or the other for CEA or CAS in any patient population [1]
- Summary
- CAS and CEA appear to be equally effective treatments in most patients
- In the CREST trial that enrolled both symptomatic and asymptomatic patients, CAS had a higher risk of stroke in the periprocedural period, where CEA had a higher risk of heart attack. Patients older than 70 did better with CEA, while patients younger than 70 did better with CAS.
- In the ACT I and ACST-2 trials, asymptomatic patients did equally well with CAS or CEA. In the ICSS trial that enrolled symptomatic patients, CEA and CAS were equivalent for the primary outcome, but CEA was superior for the secondary outcome of any stroke.
- CAROTID ARTERY OCCLUSION AND NEAR-OCCLUSION
- Overview
- In some cases, the carotid artery may be completely occluded or near-occlusion. In the medical literature, the definition of near-occlusion is not standardized.
- On ultrasound, near-occlusion is sometimes mistaken for total occlusion. If occlusion or near-occlusion is seen on ultrasound, the AHA recommends further studies with CT angiography, MR angiography, or angiography.
- In patients with chronic total occlusion, CEA or CAS is not recommended
- In patients with near-occlusion, the treatment will depend on the experience of the treating surgeon. In the pooled analysis of CEA trials involving symptomatic patients (see pooled analysis of CEA trials above), patients with near-occlusion were defined as 95% stenosis. Patients with near-occlusion who underwent CEA had worse outcomes at 5 years, although the results were not statistically significant.
- An observational study published in 2015 followed 316 patients who developed carotid artery occlusion. Of those patients, only 1 experienced a stroke at the time of occlusion. During an average follow-up of 2.56 years, only 3 patients experienced an ipsilateral stroke. This low incidence of stroke (1.2%) is less than the risk that occurs with carotid stenting or endarterectomy. [PubMed abstract]
- Summary
- While complete carotid artery occlusion sounds quite ominous, it does not appear to portend a detrimental outcome
- Carotid stenting and endarterectomy in patients with near-occlusion may be harmful
- For now, all patients with occlusion or near-occlusion should have optimal medical therapy that includes antiplatelet drugs, statins, and other risk factor management
- BIBLIOGRAPHY
- 1 - PMID 21282493
- 2 - PMID 8133624 - JAMA bruit study
- 3 - USPSTF website
- 4 - PMID 12531577 - pooled analysis of CEA studies
- 5 - PMID 15135594 - ACST study
- 6 - PMID 20505173 - CREST study
- 7 - PMID 25453443 - ICSS study
- 8 - PMID 26890472 - CREST 10 year f/u
- 9 - PMID 26886419 - ACT I trial
- 10 - PMID 35608581 - Incidence of Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention, JAMA (2022)