Prevalence, predictors, and prognosis of symptomatic intracranial stenosis in patients with transient ischaemic attack or minor stroke: a population-based cohort study

Robert Hurford, Frank J Wolters, Linxin Li, Kui Kai Lau, Wilhelm Küker, Peter M Rothwell, Oxford Vascular Study Phenotyped Cohort, Robert Hurford, Frank J Wolters, Linxin Li, Kui Kai Lau, Wilhelm Küker, Peter M Rothwell, Oxford Vascular Study Phenotyped Cohort

Abstract

Background: Symptomatic intracranial stenosis was perceived to convey a high risk of recurrent stroke, but two previous trials (SAMMPRIS and VISSIT) did not show superiority of intracranial stenosis stenting over intensive medical management alone. These findings were partly due to a lower than expected risk of recurrent stroke without stenting, possibly reflecting the young age of recruits (median age <60 years), and raise questions about generalisability to routine clinical practice. We therefore studied the age-specific prevalence, predictors, and prognosis of symptomatic intracranial stenosis in a population-based cohort of patients with transient ischaemic attack and minor stroke on intensive medical management.

Methods: The Oxford Vascular Study (OXVASC) is a prospective incidence cohort study of all vascular events in a population of 92 728 people residing in Oxfordshire, UK. All patients, irrespective of age, with transient ischaemic attack and minor ischaemic stroke occurring between March 1, 2011, and March 1, 2018 (follow-up to Sept 28, 2018), were ascertained with multiple methods, including assessment in a dedicated daily emergency clinic and daily review of all hospital admissions. Imaging was by MR angiography of the intracranial and cervicocranial arteries, by CT angiography if MR angiography was contraindicated, and by transcranial Doppler and carotid ultrasound if CT angiography was contraindicated. All patients received intensive medical treatment without stenting, and those with intracranial vascular imaging were analysed in our study, which assessed the age-specific prevalence of 50-99% intracranial stenosis and the associated stroke risk of 50-99% and 70-99% stenosis (adjusted for age and vascular risk factors) during follow-up to Sept 28, 2018.

Findings: Of 1368 eligible patients with intracranial vascular imaging, 241 (17·6%) had 385 50-99% symptomatic or asymptomatic intracranial stenosis. The prevalence of symptomatic 50-99% intracranial stenosis increased from 29 (4·9%) of 596 at younger than 70 years to 10 (19·6%) of 51 at 90 years or older (ptrend<0·0001). Of 94 patients with 50-99% symptomatic intracranial stenosis, 14 (14·9%) had recurrent strokes (12 ischaemic and two haemorrhagic) during a median follow-up of 2·8 years (IQR 1·5-4·6). Although symptomatic intracranial stenosis conveyed an increased risk of ischaemic stroke compared with no intracranial stenosis (adjusted hazard ratio 1·43, 95% CI 1·04-1·96), the risk of same-territory ischaemic stroke in patients with 70-99% symptomatic intracranial stenosis tended to be less than those reported in the non-stenting groups of the previous trials (1-year risk 5·6% [95% CI 0·0-13·0] vs 9·4% [3·1-20·7] in VISSIT; 2-year risk 5·6% [0·0-13·0] vs 14·1% [10·1-19·4] in SAMMPRIS).

Interpretation: The 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.

Funding: Wellcome Trust, Wolfson Foundation, British Heart Foundation, National Institute for Health Research, National Institute for Health Research Oxford Biomedical Research Centre, Association of British Neurologists.

Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1
Figure 1
Age-specific prevalence of extracranial and intracranial stenosis (A) 50–99% symptomatic, asymptomatic, and no intracranial stenosis. (B) Proximal extracranial internal carotid artery stenosis, extracranial vertebral artery stenosis, 50–99% intracranial stenosis, and any stenosis (extracranial or intracranial).
Figure 2
Figure 2
Risk of recurrent ischaemic stroke in patients with 50–99% symptomatic intracranial stenosis and those without intracranial stenosis Graphs show the 7-year risk of recurrent ischaemic stroke in all patients (A) and excluding those with atrial fibrillation or cardioembolic cause (B).

References

    1. Holmstedt CA, Turan TN, Chimowitz MI. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2013;12:1106–1114.
    1. Amarenco P, Lavallée PC, Monteiro Tavares L. Five-year risk of stroke after TIA or minor ischemic stroke. N Engl J Med. 2018;378:2182–2190.
    1. Suwanwela NC, Chutinetr A. Risk factors for atherosclerosis of cervicocerebral arteries: intracranial versus extracranial. Neuroepidemiology. 2003;22:37–40.
    1. Huang YN, Gao S, Li SW. Vascular lesions in Chinese patients with transient ischemic attacks. Neurology. 1997;48:524–525.
    1. Liu HM, Tu YK, Yip PK, Su CT. Evaluation of intracranial and extracranial carotid steno-occlusive diseases in Taiwan Chinese patients with MR angiography: preliminary experience. Stroke. 1996;27:650–653.
    1. Wong KS, Li H. Long-term mortality and recurrent stroke risk among Chinese stroke patients with predominant intracranial atherosclerosis. Stroke. 2003;34:2361–2366.
    1. Chimowitz MI, Lynn MJ, Derdeyn CP. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med. 2011;365:993–1003.
    1. Zaidat OO, Fitzsimmons B-F, Woodward BK. Effect of a balloon-expandable intracranial stent vs medical therapy on risk of stroke in patients with symptomatic intracranial stenosis: the VISSIT randomized clinical trial. JAMA. 2015;313:1240–1248.
    1. Derdeyn CP, Chimowitz MI, Lynn MJ. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet. 2014;383:333–341.
    1. Kernan WN, Ovbiagele B, Black HR. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2014;45:2160–2236.
    1. Intercollegiate Stroke Working Party . Royal College of Physicians; London: 2016. National clinical guideline for stroke.
    1. Turan TN, Cotsonis G, Lynn MJ. Intracranial stenosis: impact of randomized trials on treatment preferences of US neurologists and neurointerventionists. Cerebrovasc Dis. 2014;37:203–211.
    1. Schillinger G, Hagenmeyer E-G, Pritzkau A, Friedrich J. Do study results translate into practice? Intracranial stenting in Germany. Int J Technol Assess Health Care. 2017;33:222–226.
    1. Qureshi AI. Interpretation and implications of the prematurely terminated Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in the Intracranial Stenosis (SAMMPRIS) trial. Neurosurgery. 2012;70:E264–E268.
    1. Abou-Chebl A, Steinmetz H. Critique of “Stenting versus aggressive medical therapy for intracranial arterial stenosis” by Chimowitz et al in the new England Journal of Medicine. Stroke. 2012;43:616–620.
    1. Chimowitz MI, Lynn MJ, Howlett-Smith H. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352:1305–1316.
    1. Chaturvedi S, Turan TN, Lynn MJ. Do patient characteristics explain the differences in outcome between medically treated patients in SAMMPRIS and WASID? Stroke. 2015;46:2562–2567.
    1. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project—1981–86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 1990;53:16–22.
    1. Rothwell PM, Coull AJ, Silver LE. Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study) Lancet. 2005;366:1773–1783.
    1. Béjot Y, Mehta Z, Giroud M, Rothwell PM. Impact of completeness of ascertainment of minor stroke on stroke incidence: implications for ideal study methods. Stroke. 2013;44:1796–1802.
    1. Coull AJ, Silver LE, Bull LM, Giles MF, Rothwell PM. Direct assessment of completeness of ascertainment in a stroke incidence study. Stroke. 2004;35:2041–2045.
    1. Adams HPJ, Jr, Bendixen BH, Kappelle LJ. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24:35–41.
    1. WHO . World Health Organization; Geneva: 1971. Cerebrovascular diseases—prevention, treatment, and rehabilitation.
    1. Feldmann E, Wilterdink JL, Kosinski A. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial. Neurology. 2007;68:2099–2106.
    1. Lau K-K, Li L, Lovelock CE. Clinical correlates, ethnic differences, and prognostic implications of perivascular spaces in transient ischemic attack and ischemic stroke. Stroke. 2017;48:1470–1477.
    1. Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol. 2000;21:643–646.
    1. Mazighi M, Tanasescu R, Ducrocq X. Prospective study of symptomatic atherothrombotic intracranial stenoses: the GESICA study. Neurology. 2006;66:1187–1191.
    1. Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?”. Lancet. 2005;365:82–93.
    1. Turan TN, Nizam A, Lynn MJ. Relationship between risk factor control and vascular events in the SAMMPRIS trial. Neurology. 2017;88:379–385.
    1. NICE . National Institute for Health and Care Excellence; 2019. Stroke and transient ischaemic attack in over 16s: Diagnosis and initial management.
    1. Sharma M, Hart RG, Connolly SJ. Stroke outcomes in the COMPASS trial. Circulation. 2019;139:1134–1145.
    1. Koopman C, Vaartjes I, Heintjes EM. Persisting gender differences and attenuating age differences in cardiovascular drug use for prevention and treatment of coronary heart disease, 1998–2010. Eur Heart J. 2013;34:3198–3205.
    1. Salami JA, Warraich H, Valero-Elizondo J. National trends in statin use and expenditures in the US adult population from 2002 to 2013: insights from the Medical Expenditure Panel Survey. JAMA Cardiol. 2017;2:56–65.
    1. Hurford R, Li L, Lovett N, Kubiak M, Kuker W, Rothwell PM. Prognostic value of “tissue-based” definitions of TIA and minor stroke: population-based study. Neurology. 2019;92:e2455–ee261.
    1. Nederkoorn PJ, Elgersma OEH, Mali WPTM, Eikelboom BC, Kappelle LJ, van der Graaf Y. Overestimation of carotid artery stenosis with magnetic resonance angiography compared with digital subtraction angiography. J Vasc Surg. 2002;36:806–813.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi