ISCHEMIC STROKE / PREVENTION
Management of asymptomatic carotid stenosis
Created 03/01/2022, last revision 04/02/2023
Stroke risk and prevalence of asymptomatic carotid stenosis
Stroke risk and prevalence of asymptomatic carotid stenosis
- besides the increased risk of stroke, patients with asymptomatic carotid stenosis have a higher risk of MI as well ⇒ intensive systemic therapy is essential
- the prevalence of asymptomatic stenosis > 50% is 2-8%, the prevalence of asymptomatic stenosis > 80% is 1-2%
- the prevalence of stenosis > 50% increases with age
- < 60 years – 0.5% , > 80 years – 10%
- risk of stroke in patients with asymptomatic carotid stenosis > 50% is about 1-2%/year
- according to a population-based study and meta-analysis, the risk of stroke increases with the degree of stenosis – the risk of 80-99% stenosis is higher than that of 50-79% stenosis [Howard, 2021]
- see below for individual parameters of high-risk plaques
- relevant revascularization trials
- ACAS
- ARR 6% /5 years (5.1% vs 11%)
- ACST-1
- ARR 5.4% /5 years (6.4 vs 11.8%) with an operative risk of 2.8% [Halliday, 2004]
- ARR 4.5% /10 years (13.4% vs 17.9%) [ [Halliday, 2010]
- ACST-2
- n=3625 ( 1811 allocated to CAS, 1814 to CEA)
- procedural stroke: 1% disabling stroke/death, 2% had a non-disabling procedural stroke
- Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke
- the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable
- SPACE-2 trial was terminated prematurely due to the lack of funding
- ACAS
- major ongoing trials:
- CREST-2 (medication vs. CEA+medication/CAS + medication)
→ management of patients with carotid stenosis undergoing surgery in GA or in ECC
Best medical therapy
- best medical therapy (BMT) is the mainstay of carotid stenosis management (at the same time, it leads to a reduced risk of MI)
- antiplatelet drugs
- intensive vascular risk factors treatment
- relatively low risk of stroke was reported with such approach (~1.68%/year) [Raman, 2013]
Antiplatelet drugs
- aspirin 100-300 mg/d
- aspirin intolerance or contraindication: clopidogrel or ticlopidine
- clopidogrel resistance/allergy: consider ticagrelor (BRILIQUE)
→ antiplatelet drugs
Management of vascular risk factors
- target BP < 135/85 mm Hg (130/80 mm Hg in diabetes)
- prefer ACE-I or sartans
- prefer ACE-I or sartans
- statin → target lipid values
- target glycosylated Hb < 53 mmol/mol in diabetes + management of insulin resistance
- no smoking
- obesity control
- according to some recommendations, the target BMI is <20!)
- waist circumference female/ male <80/<94 cm
- physical activity (>30 min/day)
Carotid artery revascularization
- carotid artery revascularisation (CAR) = carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS)
- carotid revascularisation should be performed only in a ward with low perioperative complications (<3% in asymptomatic stenoses)
- CEA/CAS has similar safety, but CEA seems little safer (ACST-2)
- the SAPPHIRE and CREST trials demonstrated the similar safety of CAS and CEA
- ACT 1 and ACST-2 trials demonstrated comparable safety even in asymptomatic stenoses [Rosenfield, 2016]
- on the other hand, according to an analysis of 5 randomized trials, CEA appears somewhat safer than CAS [Moresoli, 2017]
- patients with more extensive white matter lesions on CT/MRI (ARWMC score ≥ 7) should rather be managed with CEA (ICSS trial)
- when considering any intervention, take into account several aspects which may help to select patients with the highest profit from revascularisation (→ see here)
- degree of stenosis + plaque vulnerability should be evaluated (Brinjikji, 2016)
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All cited markers of high stroke risk in relation to asymptomatic carotid stenosis:
- lack specificity
- have not been assessed in conjunction with the current optimal medical intervention
- have not been shown in randomized trials to identify those who benefit from a carotid revascularization procedure in addition to optimal medical intervention
Stenosis degree
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Progression over time
- risk of progression of carotid stenosis is substantial and increases with time
- several studies show a higher risk of stroke in progressive stenoses > 80%
- rapidly progressive stenoses, in particular, seem to be associated with a higher risk of ischemic stroke
- the data justify the use of serial duplex scans to follow carotid stenosis; there is no consensus on appropriate intervals
- according to different recommendations, the scan should be repeated every 6-12 months in case of stenosis > 50% (AHA/ASA 2014 IIa/C)
Plaque morphology
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Proof of microembolization on TCD/TCCD
- the association of embolic signals with the risk of infarction has been demonstrated in both symptomatic and asymptomatic stenoses
[Markus, 2017]
- detection of ≥ 2 embolic signals per hour indicates an unstable plaque or plaque with thrombosis
- annual stroke risk is up to 8%
- embolic signals are more common in unstable, hypoechoic, exulcerated, poorly calcified plaques
- using TCD Holter could be helpful in these conditions
Evidence of silent ischemia
- according to some authors, the incidence of silent ischemia on CT/MRI correlates with the degree of stenosis and the type of plaque (especially exulcerated plaques)
- MRI is more sensitive than CT
- according to the ACSRS trial, for stenosis > 60%, the average incidence of stroke in patients with silent ischemia is 3.6%/year compared to 1.3%/year in those without silent ischemia
- no difference was demonstrated for stenosis < 60%
- in contrast, in the ACAS trial, silent ischemia was not related to stenosis severity
- although the benefit of revascularisation in patients with silent lesions has not been demonstrated by studies, in clinical practice, their findings are usually considered a supportive factor for the indication of CEA/CAS
Impact of contralateral carotid stenosis or occlusion
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Gender
- in the ACAS trial, women had a higher operative risk than men ( 3.6% vs. 1.7%); some other smaller studies have reported similar results
- other studies have not confirmed those findings
- there is no solid consensus, but there is a tendency toward greater restraint in women
Age
- the advanced age is not an absolute contraindication to CEA/CAS; the patient’s biological status, life expectancy, and other factors must be considered
- surgery is more common among patients < 75 years of age
- in the ACAS trial, age > 80 years was a contraindication
- in the ACST trial, the benefit was relatively small in patients > 75 years (ARR 3.3%/5 years)
- for asymptomatic stenoses, a higher mortality rate was reported in patients >75 years compared to those <75 years of age [Rajamani, 2013]
- in the ACAS trial, age > 80 years was a contraindication
Intracranial flow and vasomotor reactivity (CVR)
- the data indicate a higher risk of stroke in patients with impaired cerebral vasomotor reactivity (VMR or CVR) and impaired intracranial flow
[Gupta, 2012]
- ~4x higher risk of stroke/TIA (5.7% per year with an average follow-up of 24 months)
- methods used to assess VMR:
- neurosonological examinations
- hyperventilation/apnea test during TCCD examination
- acetazolamide (ACZ) test
- hyperventilation/apnea test during TCCD examination
- MRA+MR perfusion
- CT perfusion performed after i.v. acetazolamide challenge
[Kang, 2008]
- severe stenosis may sometimes manifest as a false ischaemic penumbra (FIP) on baseline CTP [Mosqueira, 2017]
- SPECT performed after i.v. acetazolamide challenge
- neurosonological examinations
