Intensive medical management of intracranial arterial stenosis
Authors: Shinichiro Uchiyama
Journal: The Lancet Neurology (2020)

Intracranial arterial stenosis increases the risk of stroke, and stroke recurs more frequently in patients with symptomatic intracranial arterial stenosis than in those without.1Amarenco P Lavallee PC Tavares LM et al.Five-year risk of stroke after TIA or minor ischemic stroke.N Engl J Med. 2018; 378: 2182-2190Crossref PubMed Scopus (166) Google Scholar However, few vascular imaging studies of intracranial arterial stenosis have been done in Caucasian populations, because it is less common than in Asian populations.2Hoshino T Uchiyama S Wong LKS et al.Differences in characteristics and outcomes between Asian and non-Asian patients in the TIAregistry.org.Stroke. 2017; 48: 1779-1787Crossref PubMed Scopus (13) Google Scholar, 3Uchiyama S Hoshino T Sissani L et al.Japanese versus non-Japanese patients with transient ischemic attack or minor stroke: subanalysis of TIAregistry.org.J Stroke Cerebrovasc Dis. 2019; 28: 2232-2241Summary Full Text Full Text PDF PubMed Scopus (8) Google Scholar In The Lancet Neurology, Robert Hurford and colleagues4Hurford R Wolters FJ Li L et al.Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population-based cohort study.Lancet Neurol. 2020; 19: 413-421Summary Full Text Full Text PDF PubMed Scopus (43) Google Scholar report the results of a population-based longitudinal cohort study investigating the age-specific prevalence, predictors, and prognosis of intracranial arterial stenosis exclusively in Caucasian patients (the Oxford Vascular Study [OXVASC] cohort) with transient ischaemic attack or minor stroke on intensive medical management. This study also confirms the risk estimates for stroke recurrence from two previous randomised controlled trials (SAMMPRIS5Chimowitz MI Lynn MJ Derdeyn CP et al.Stenting versus aggressive medical therapy for intracranial arterial stenosis.N Engl J Med. 2011; 365: 993-1003Crossref PubMed Scopus (1269) Google Scholar and VISSIT6Zaidat OO Fitzsimmons B-F Woodward BK et al.Effect of balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial.JAMA. 2015; 313: 1240-1248Crossref PubMed Scopus (306) Google Scholar) in patients with intracranial arterial stenosis that compared stenting with intensive medical management, and supports the role of intensive medical management over stenting, irrespective of age. SAMMPRIS5Chimowitz MI Lynn MJ Derdeyn CP et al.Stenting versus aggressive medical therapy for intracranial arterial stenosis.N Engl J Med. 2011; 365: 993-1003Crossref PubMed Scopus (1269) Google Scholar and VISSIT6Zaidat OO Fitzsimmons B-F Woodward BK et al.Effect of balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial.JAMA. 2015; 313: 1240-1248Crossref PubMed Scopus (306) Google Scholar showed that stenting was not superior to intensive medical management in patients with intracranial arterial stenosis. However, the lower than expected rates of stroke recurrence in the intensive medical management groups were controversial because of the recruitment of patients younger than 60 years in these trials. Thus, stenting is still commonly done in many countries without clear evidence of its superiority. OXVASC reported an even lower rate of stroke than those in the intensive medical management groups of the SAMMPRIS and VISSIT trials (1-year risk 5·6% vs 9·4% in VISSIT; 2-year risk 5·6% vs 14·1% in SAMMPRIS), despite including patients older than 60 years, which supports the generalisability of the trial results to routine clinical practice for a wide age range of patients. Patients in OXVASC received intensive medical management similar to that of SAMMPRIS and VISSIT, which consisted of dual antiplatelet therapy with aspirin and clopidogrel for the first month, followed by monotherapy with aspirin or clopidogrel thereafter. Medical management also included aggressive statin treatment, strict blood pressure control (<130/80 mmHg), smoking cessation, and exercise and dietary advice. These multiple interventions might have contributed to the reduced risk of recurrent stroke in patients in the OXVASC cohort. However, the WEAVE trial7Alexander MJ Zauner A Chaloupka JC et al.WEAVE trial: final results in 152 on-label patients.Stroke. 2019; 50: 889-894Crossref PubMed Scopus (144) Google Scholar has shown a low rate of periprocedural stroke, bleeding, and death in patients with symptomatic intracranial arterial stenosis. The WEAVE trial is a post-market surveillance trial mandated by the US Food and Drug Administration (FDA) to assess the periprocedural safety of the Wingspan Stent system in patients who met the FDA on-label usage criteria, which included age 22–80 years, stenosis of 70–99%, modified Rankin Scale score of 3 or less, and two or more strokes in the vascular territory of the stenotic lesion with at least one stroke while on medical therapy, and stenting of the lesion 8 days or more after the last stroke. SAMMPRIS, however, included patients who did not meet the FDA on-label usage criteria for stenting. Stroke due to intracranial arterial stenosis or carotid stenosis is classified as large artery atherosclerosis in the subtypes of ischaemic stroke. Data from TIAregistry.org, an international observational registry of patients with acute transient ischaemic attack or minor stroke, showed that the rate of recurrent stroke is higher in patients with large artery atherosclerosis (atherothrombotic stroke and transient ischaemic attack) than in those with other stroke subtypes.1Amarenco P Lavallee PC Tavares LM et al.Five-year risk of stroke after TIA or minor ischemic stroke.N Engl J Med. 2018; 378: 2182-2190Crossref PubMed Scopus (166) Google Scholar This registry-based analysis also showed a sustained risk of cardiovascular events over a period of 5 years, with half of the events occurring during years 2–5, despite adherence to current guidelines.1Amarenco P Lavallee PC Tavares LM et al.Five-year risk of stroke after TIA or minor ischemic stroke.N Engl J Med. 2018; 378: 2182-2190Crossref PubMed Scopus (166) Google Scholar Overall, this evidence suggests that the frequency of recurrent strokes needs to be reduced through more intensive secondary prevention strategies. Atherothrombosis is a polyvascular disease, which includes atherothrombotic stroke, transient ischaemic attack, coronary artery disease, and peripheral artery disease. The risk of vascular events in patients with atherothrombosis increases as the number of involved vascular beds increases.8Bhatt DL Steg PG Ohman EM et al.International prevalence, recognition and treatment of cardiovascular risk factors in out-patients with atherothrombosis.JAMA. 2006; 295: 180-189Crossref PubMed Scopus (1347) Google Scholar In the OXVASC cohort, any vascular disease, history of stroke or transient ischaemic attack, peripheral vascular disease, and ischaemic heart disease were more common in patients with intracranial arterial stenosis than in those without.4Hurford R Wolters FJ Li L et al.Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population-based cohort study.Lancet Neurol. 2020; 19: 413-421Summary Full Text Full Text PDF PubMed Scopus (43) Google Scholar In a subgroup analysis of TIAregistry.org,9Hoveanu C Lavellee PC Rothwell PM et al.Symptomatic patients remain at substantial risk of arterial disease complications before and after endarterectomy or stenting.Stroke. 2017; 48: 1005-1010Crossref PubMed Scopus (7) Google Scholar the risk of vascular events remained high after carotid endarterectomy or stenting in patients with symptomatic carotid stenosis. Thus, the risk of vascular events in vascular beds might not be reduced by local stenting in patients with symptomatic intracranial arterial stenosis. Taken together, to reduce the residual risk of composite vascular events in patients with intracranial arterial stenosis, more intensive antiplatelet therapy and total risk management are needed regardless of concomitant stenting. I declare no competing interests. Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population-based cohort studyThe prevalence of 50–99% symptomatic intracranial stenosis increases steeply with age in predominantly Caucasian patients with transient ischaemic attack and minor ischaemic stroke. However, the risk of recurrent stroke on intensive medical treatment of symptomatic intracranial stenosis is consistent with the two previous randomised controlled trials in younger cohorts, supporting the generalisability of the trial results to routine practice. Full-Text PDF Open Access