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New insights in natural history and treatment of asymptomatic moderate carotid artery stenosis

A large retrospective community-based cohort study showed a modest risk for ipsilateral stroke in patients with moderate asymptomatic carotid stenosis

A recently published retrospective community-based cohort study (Kaiser Permanente, Northern California) aimed to assess the long-term risk of ipsilateral stroke in patients with asymptomatic moderate cervical internal carotid artery stenosis, defined as 50% to 69% vessel diameter reduction (per the NASCET criteria).

The cohort included 11614 arteries with moderate stenosis in 9803 patients (mean age 74.2±9.9 years, 51.4% women) investigated between 2008-2012. The mean follow-up time was 5.1±2.9 years. The overall mortality rate was 44.5% (4367 patients).

During the follow-up period, 180 ipsilateral ischemic strokes were attributed to carotid stenosis (crude annual risk 0.31% [95% CI, 0.21%–0.41%]), while a total of 599 ischemic strokes were attributed to other causes (due to occurrence in other/multiple territories or other identifiable aetiologies, such as atrial fibrillation).

Using a competing risk model, the cumulative risk for carotid-related stroke was 1.2% (95% CI, 1.0%–1.4%) at 5 years and 2.0% (95% CI, 1.7%–2.4%) at 10 years.

The study showed a moderate rate of disease progression, which was defined as progression of stenosis to 70% to 99% (severe stenosis) or 100% (occlusion) on subsequent imaging. Follow up studies performed in 5951 (60.7%) patients revealed stenosis progression in 1674 arteries (14.4% of the total number of arteries, 28% of those with follow-up studies). The mean time to stenosis progression was 2.6±2.1 years. Significant predictors of disease progression on multivariable analysis of the entire cohort included age at the initial diagnosis of moderate stenosis, current or former tobacco use and severe contralateral carotid artery stenosis/occlusion.

The core limitation of this study was the observational design.

The SPACE-2 trial, a multicentre, randomised controlled trial, compared carotid endarterectomy (CEA) to carotid artery stenting (CAS) and best medical therapy (BMT) alone for moderate-to-severe asymptomatic carotid artery stenosis. It included patients with asymptomatic carotid artery stenosis at the distal common carotid artery or the extracranial internal carotid artery of at least 70% according to ECST criteria (equivalent to 50–99% per the NASCET criteria).

The 5-year cumulative incidence of ipsilateral ischaemic stroke was 2·0% (95% CI 0·7–5·2) with CEA, 4·4% (2·2–8·6) with CAS, and 3·1% (95% CI 1·0–9·4) with BMT alone. Both CEA and CAS failed to show a clear advantage over BMT in SPACE-2.

In conclusion, moderate asymptomatic stenosis seems to be a poor predictor of occurrence of ipsilateral stroke and revascularisation does not show an advantage over BMT. By including recurrent stroke of other aetiologies, previous studies might have overestimated the risk of large vessel-associated stroke in this setting.


Key Points:

  • Moderate asymptomatic carotid stenosis is associated with a modest rate of ipsilateral stroke.
  • Interventions (both CEA and CAS) do not show any advantage over BMT alone in moderate-to-severe asymptomatic carotid artery stenosis.
  • By including recurrent stroke of other aetiologies, previous studies might have overestimated the risk of recurrent stroke.
  • Large clinical trials are needed to determine if CAS and CEA provide treatment benefits in comparison to present best medical therapy.


  • Gologorsky RC, Lancaster E, Tucker LY, Nguyen-Huynh MN, Rothenberg KA, Avins AL, Kuang HC, Chang RW. Natural History of Asymptomatic Moderate Carotid Artery Stenosis in a Large Community-Based Cohort. Stroke. 2022 Sep;53(9):2838-2846. doi: 10.1161/STROKEAHA.121.038426. Epub 2022 Jun 8. PMID: 35674045.
  • Reiff T, Eckstein HH, Mansmann U, Jansen O, Fraedrich G, Mudra H, Böckler D, Böhm M, Debus ES, Fiehler J, Mathias K, Ringelstein EB, Schmidli J, Stingele R, Zahn R, Zeller T, Niesen WD, Barlinn K, Binder A, Glahn J, Hacke W, Ringleb PA; SPACE-2 Investigators. Carotid endarterectomy or stenting or best medical treatment alone for moderate-to-severe asymptomatic carotid artery stenosis: 5-year results of a multicentre, randomised controlled trial. Lancet Neurol. 2022 Oct;21(10):877-888. doi: 10.1016/S1474-4422(22)00290-3. PMID: 36115360.

Dr. Cătălina Cîmpanu

Simon Fandler-Höfler, Medical University of Graz, Austria

Publish on behalf of the Scientific Panel on Stroke