title: Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.
abstract: BACKGROUND
  Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy.
  
  
  METHODS
  Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470.
  
  
  RESULTS
  1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7.
  
  
  CONCLUSIONS
  The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions.
  
  
  BACKGROUND
  Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.
authors.affiliation: Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ederle
authors.affiliation: Lysholm Department of Neuroradiology, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Indran
authors.initials: I
authors.lastname: Davagnanam
authors.affiliation: Utrecht Stroke Center, Departments of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, the Netherlands.
authors.forename: H Bart
authors.initials: HB
authors.lastname: van der Worp
authors.affiliation: Neurology Department, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Venables
authors.affiliation: Department of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Lyrer
authors.affiliation: Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: Roland L
authors.initials: RL
authors.lastname: Featherstone
authors.affiliation: Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK. Electronic address: martin.brown@ucl.ac.uk.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Brown
authors.affiliation: Stroke Research Group, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK; Lysholm Department of Neuroradiology, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: H Rolf
authors.initials: HR
authors.lastname: Jäger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016893:Carotid Stenosis / Q000473:pathology / Q000601:surgery*; D002548:Cerebral Revascularization / Q000009:adverse effects*; D016894:Endarterectomy, Carotid / Q000009:adverse effects*; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000150:complications* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology* / Q000473:pathology; D012306:Risk; D016037:Single-Blind Method; D015607:Stents / Q000009:adverse effects*; D020521:Stroke / Q000145:classification / Q000209:etiology* / Q000473:pathology; D016896:Treatment Outcome