ISCHEMIC STROKE / PREVENTION

Management of asymptomatic carotid stenosis

Created 03/01/2022, last revision 07/11/2023

  • carotid artery atherosclerotic disease is a substantial stroke risk factor (classified as 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 CV 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

Carotid artery stenosis (ultrasound, CTA, MRA, DSA)
  • 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

Management of patients with carotid artery stenosis undergoing surgical intervention

  • 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
  • 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)
  • 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)

→ antiplatelet drugs

Anticoagulant drugs

  • antiplatelet + low-dose anticoagulant:
    • ASA + rivaroxaban 2×2.5 mg in selected patients
      • in the COMPASS trial, carotid disease included both asymptomatic stenoses 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
  • 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
  • lipid-lowering therapy 
  • 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 (e.g., Med-Diet)
    • physical activity
      • 150 min/wk of moderate aerobic or 75 min/wk of vigorous aerobic activity

→ overview of most important vascular risk factors

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  Microembolic signal detected on TCCD Microembolic signal detected on power motion-mode Doppler (PMD-TCD)  [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]

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 Impaired intracranial flow in a patient with high-grade carotid stenosis [Gupta, 2012]
    • ~4x higher risk of stroke/TIA (5.7% per year with an average follow-up of 24 months)
  • methods used to assess CVR (VMR):
    • transcranial doppler (TCD/TCCD)
      • hyperventilation/apnea test
      • breath holding test
      • acetazolamide (ACZ)
    • other imaging methods performed before and after administration of the vasodilatory agent (acetazolamide-challenged methods)

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Management of asymptomatic carotid stenosis
link: https://www.stroke-manual.com/asymptomatic-carotid-stenosis/