ISCHEMIC STROKE / PREVENTION
Management of asymptomatic carotid stenosis
Created 03/01/2022, last revision 27/02/2023
- carotid artery atherosclerotic disease is a substantial stroke risk factor (TOAST 1)
- classification of carotid artery disease
- asymptomatic x symptomatic (signs/symptoms of cerebral or ocular ischemia in the past 6 months)
- low risk x high risk
- high risk features:
- significant carotid stenosis of ≥ 50% or an increased carotid IMT of 1.5 mm
- detection of vulnerable plaque (characteristics are discussed below)
- additional uncontrolled CV risk factors (atrial fibrillation, diabetes mellitus, metabolic syndrome, etc.)
Stroke risk and prevalence of asymptomatic carotid stenosis
- the prevalence of carotid artery atherosclerotic disease depends on the population studied and the stenosis threshold used for inclusion
- the prevalence of asymptomatic stenosis > 50% is 2-8%, and the prevalence of asymptomatic stenosis > 80% is 1-2%
- the prevalence of stenosis > 50% increases with age
- < 60 years – 0.5% , > 80 years – 10%
- the risk of stroke in patients with asymptomatic carotid stenosis > 50% is about 1-2%/year (rate of coronary events is 7%)
- compared to symptomatic stenosis, the risk is much lower
- 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
- in addition to the increased risk of stroke, patients with asymptomatic carotid stenosis also have an increased risk of MI ⇒ intensive systemic therapy is essential
- in general, prophylactic CEA is not required before surgery using general anesthesia (GA) or extracorporeal circulation (ECC) → carotid endarterectomy
Screening for asymptomatic carotid stenosis
- screening for asymptomatic carotid stenosis in the general population is not recommended by the U.S. Preventive Services Task Force (unknown cost-benefit)
- the situation may vary from country to country.
- it is recommended to screen selected patients with:
- symptomatic peripheral artery disease (PAD), coronary artery disease (CAD), or atherosclerotic aortic aneurysm
- ≥ 2 of the following CV risk factors, including arterial hypertension, hyperlipidemia, smoking, family history of early-onset atherosclerotic disease in a first-degree relative, or family history of ischemic stroke
- symptomatic peripheral artery disease (PAD), coronary artery disease (CAD), or atherosclerotic aortic aneurysm
- repeated duplex examination:
- annually assess patients with carotid stenosis >50% for progression or regression and response to therapeutic intervention
- patients with normal/mildly increased baseline IMT should not have repeat carotid Doppler (because of the very slow rate of IMT increase)
Best medical therapy
- best medical therapy (BMT) is the mainstay of carotid stenosis management (it also leads to a reduced risk of MI)
- antiplatelet drugs
- intensive management of vascular risk factors
- the relatively low risk of stroke was reported with such an approach (~1.68%/year) [Raman, 2013]
Antithrombotic therapy
Antiplatelet drugs
- aspirin 75-325 mg/d
- aspirin intolerance or contraindication: clopidogrel (75mg) or ticlopidine
- clopidogrel resistance/allergy: consider ticagrelor (BRILIQUE)
Anticoagulant drugs
- antiplatelet + low-dose anticoagulant:
- ASA + rivaroxaban 2×2.5 mg in selected patients
- in the COMPASS trial, carotid disease included both asymptomatic stenosis and patients with previous revascularization. The combination was maximally effective in patients with ‘symptomatic PAD’ defined as the co-existence of symptomatic peripheral artery disease of lower
extremities and carotid artery disease
- in the COMPASS trial, carotid disease included both asymptomatic stenosis and patients with previous revascularization. The combination was maximally effective in patients with ‘symptomatic PAD’ defined as the co-existence of symptomatic peripheral artery disease of lower
- ASA + rivaroxaban 2×2.5 mg in selected patients
- anticoagulants alone: not recommended
- antiplatelets + standard-dose anticoagulants: not recommended
Vascular risk factors management
- target BP < 120/80 mm Hg (if possible concerning comorbidities)
- in therapy, prefer ACE-I or sartans
- in therapy, prefer ACE-I or sartans
- lipid-lowering therapy
- LDL cholesterol target according to cardiovascular risk → target lipid values
- tight glycemic control
- target glycosylated Hb < 53 mmol/mol in diabetes + management of insulin resistance
- lifestyle interventions:
- smoking cessation
- obesity control
- according to some recommendations, the target BMI <20-24!
- waist circumference female/ male <80/<94 cm
- a healthy diet (i.e. Med-Diet)
- physical activity
- 150 min/wk of moderate aerobic or 75 min/wk of vigorous aerobic activity
Carotid artery revascularization
- carotid artery revascularisation (CAR) = carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS)
- carotid revascularisation should only be performed in a unit with low perioperative complications (<3% for asymptomatic stenosis)
- CEA and CAS have similar safety, but CEA seems to be a 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, CEA appears somewhat safer than CAS according to an analysis of 5 randomized trials [Moresoli, 2017]
- patients with more extensive white matter lesions on CT/MRI (ARWMC score ≥ 7) should be treated with CEA (ICSS trial)
- when considering any intervention, several aspects should be considered that may help to select patients with the highest benefit 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 associated with asymptomatic carotid stenosis:
- lack specificity
- have not been assessed in conjunction with the current optimal medical therapy
- have not been shown in randomized trials to identify those who will benefit from a carotid revascularization procedure in addition to optimal medical therapy
Stenosis degree
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Progression over time
- risk of stenosis progression is substantial and increases with time
- several studies showed 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 the appropriate intervals
- according to various recommendations, the scan should be repeated every 6-12 months for 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 a plaque with concurrent thrombosis
- annual stroke risk is up to 8% in such condition
- embolic signals are more common in unstable, hypoechoic, exulcerated, poorly calcified plaques
- the use of TCD Holter may 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 seen for stenosis < 60%
- in contrast, silent ischemia was not related to stenosis severity in the ACAS trial
- although the benefit of revascularisation in patients with silent lesions has not been demonstrated in trials, their detection is a supportive factor for the indication of CEA/CAS in clinical practice
Impact of contralateral carotid stenosis or occlusion
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Gender
- in the ACAS trial, women had a higher surgical 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
- 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 in 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 [Rajamani, 2013]
- in the ACAS trial, age > 80 years was a contraindication
Intracranial flow and vasomotor reactivity (CVR)
- 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:
- neurosonologic examinations
- hyperventilation/apnea test during TCCD examination
- acetazolamide (ACZ) test
- hyperventilation/apnea test during TCCD examination
- MRA+MR perfusion
- CT perfusion performed after IV acetazolamide challenge
[Kang, 2008]
- severe stenosis may sometimes manifest as false ischemic penumbra (FIP) on baseline CTP [Mosqueira, 2017]
- SPECT performed after IV acetazolamide challenge
- neurosonologic examinations