title: Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials.
abstract: BACKGROUND
  Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups.
  
  
  METHODS
  In this meta-analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis.
  
  
  RESULTS
  Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2·7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65-69 years compared with patients younger than 60 years was 2·16 (95% CI 1·13-4·13), with HRs of roughly 4·0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0·34). These changes underpinned a CAS-versus CEA periprocedural HR of 1·61 (95% CI 0·90-2·88) for patients aged 65-69 years and an HR of 2·09 (1·32-3·32) for patients aged 70-74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p≥0·09 for CAS and 0·83 for CEA), or between treatment groups (p=0·84).
  
  
  CONCLUSIONS
  In these RCTs, CEA was clearly superior to CAS in patients aged 70-74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure.
  
  
  BACKGROUND
  None.
authors.affiliation: Department of Biostatistics, UAB School of Public Health, Birmingham, AL, USA. Electronic address: ghoward@uab.edu.
authors.forename: George
authors.initials: G
authors.lastname: Howard
authors.affiliation: Cardiovascular Associates of the Southeast, Birmingham, AL, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Roubin
authors.affiliation: Clinic for Radiology and Neuroradiology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Olav
authors.initials: O
authors.lastname: Jansen
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hendrikse
authors.affiliation: Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Oxford, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Halliday
authors.affiliation: Department of Vascular Surgery, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Gustav
authors.initials: G
authors.lastname: Fraedrich
authors.affiliation: Department of Vascular and Endovascular Surgery, Vascular Center, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
authors.forename: Hans-Henning
authors.initials: HH
authors.lastname: Eckstein
authors.affiliation: Department of Neurology, Hôpital Sainte-Anne, Université Paris-Descartes, DHU Neurovasc Sorbonne Paris Cité, INSERM U894, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Calvet
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Oxford University, Oxford, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Bulbulia
authors.affiliation: Department of Neurology and Stroke Center, University Hospital Basel, Basel, Switzerland; Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Leo H
authors.initials: LH
authors.lastname: Bonati
authors.affiliation: Department of Vascular Surgery, University of Paris, XII, Hôpital Henri Mondor, Paris, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Becquemin
authors.affiliation: Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus and 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 Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Martin M
authors.initials: MM
authors.lastname: Brown
authors.affiliation: Department of Neurology, University of Heidelberg Medical School, Heidelberg, Germany.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ringleb
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Brott
authors.affiliation: Department of Neurology, Hôpital Sainte-Anne, Université Paris-Descartes, DHU Neurovasc Sorbonne Paris Cité, INSERM U894, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mas
mesh_terms: D000367:Age Factors; D002339:Carotid Arteries / Q000601:surgery*; D016894:Endarterectomy, Carotid / Q000009:adverse effects* / Q000401:mortality*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D015607:Stents / Q000009:adverse effects*; D020521:Stroke / Q000209:etiology* / Q000401:mortality*