title: Stenting versus medical treatment in patients with symptomatic vertebral artery stenosis: a randomised open-label phase 2 trial.
abstract: BACKGROUND
  Patients with a recent vertebrobasilar transient ischaemic attack or ischaemic stroke and vertebral artery stenosis of at least 50% have a high risk of future vertebrobasilar stroke. Stenting of vertebral artery stenosis is promising, but of uncertain benefit. We investigated the safety and feasibility of stenting of symptomatic vertebral artery stenosis of at least 50%, and assessed the rate of vascular events in the vertebrobasilar supply territory to inform the design of a phase 3 trial.
  
  
  METHODS
  Between Jan 22, 2008, and April 8, 2013, patients with a recent transient ischaemic attack or minor stroke associated with an intracranial or extracranial vertebral artery stenosis of at least 50% were enrolled from seven hospitals in the Netherlands in a phase 2 open-label trial with masked assessment of outcome. Patients were randomly allocated in a 1:1 ratio to stenting plus best medical treatment or best medical treatment alone by the local investigators using a web-based randomisation system. The primary outcome was the composite of vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment. The secondary outcomes were stroke in the supply territory of the symptomatic vertebral artery during follow-up, the composite outcome during follow-up, and the degree of stenosis in the symptomatic vertebral artery at 12 months. The trial is registered, number ISRCTN29597900.
  
  
  RESULTS
  The trial was stopped after inclusion of 115 patients because of new regulatory requirements, including the use of a few prespecified stent types and external monitoring, for which no funding was available. 57 patients were assigned to stenting and 58 to medical treatment alone. Three patients in the stenting group had vascular death, myocardial infarction, or any stroke within 30 days after the start of treatment (5%, 95% CI 0-11) versus one patient in the medical treatment group (2%, 0-5). During a median follow-up of 3 years (IQR 1·3-4·1), seven (12%, 95% CI 6-24) patients in the stenting group and four (7%, 2-17) in the medical treatment group had a stroke in the territory of the symptomatic vertebral artery; 11 (19%) patients in the stenting group and ten (17%) in the medical treatment group had vascular death, myocardial infarction, or any stroke. The small size of the vertebral artery and stent artifacts did not allow exact grading of restenosis on CT angiography. During the complete period of follow-up, there were 60 serious adverse events (eight strokes) in the stenting group and 56 (seven strokes) in the medical treatment alone group.
  
  
  CONCLUSIONS
  Stenting of symptomatic vertebral artery stenosis is associated with a major periprocedural vascular complication in about one in 20 patients. In the population we studied, the risk of recurrent vertebrobasilar stroke under best medical treatment alone was low, questioning the need for and feasibility of a phase 3 trial.
  
  
  BACKGROUND
  Dutch Heart Foundation.
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands. Electronic address: a.compter@umcutrecht.nl.
authors.forename: Annette
authors.initials: A
authors.lastname: Compter
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: H Bart
authors.initials: HB
authors.lastname: van der Worp
authors.affiliation: Department of Neurology, St Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: Schonewille
authors.affiliation: Department of Radiology, St Antonius Hospital, Nieuwegein, Netherlands.
authors.forename: Jan Albert
authors.initials: JA
authors.lastname: Vos
authors.affiliation: Department of Neurology, Medical Center Haaglanden, Hague, Netherlands.
authors.forename: Jelis
authors.initials: J
authors.lastname: Boiten
authors.affiliation: Department of Neurology, Academic Medical Center, Amsterdam, Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nederkoorn
authors.affiliation: Department of Neurology, University Medical Center Groningen, Groningen, Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Uyttenboogaart
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Rob T
authors.initials: RT
authors.lastname: Lo
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Ale
authors.initials: A
authors.lastname: Algra
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: L Jaap
authors.initials: LJ
authors.lastname: Kappelle
mesh_terms: D000368:Aged; D003131:Combined Modality Therapy; D057510:Endovascular Procedures / Q000009:adverse effects / Q000379:methods*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011183:Postoperative Complications; D012008:Recurrence; D015607:Stents; D020521:Stroke / Q000209:etiology*; D016896:Treatment Outcome; D014715:Vertebrobasilar Insufficiency / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*
chemical_list: D005343:Fibrinolytic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors