title: Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial.
abstract: BACKGROUND
  Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14·7%) of 224 patients in the stenting group and 13 (5·8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial.
  
  
  METHODS
  We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70-99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00576693.
  
  
  RESULTS
  During a median follow-up of 32·4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0·0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7·1% at year 1 (95% CI 0·2 to 13·8%; p=0·0428), 6·5% at year 2 (-0·5 to 13·5%; p=0·07) and 9·0% at year 3 (1·5 to 16·5%; p=0·0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group: any stroke (59 [26%] of 224 patients vs 42 [19%] of 227 patients; p=0·0468) and major haemorrhage (29 [13%]of 224 patients vs 10 [4%] of 227 patients; p=0·0009).
  
  
  CONCLUSIONS
  The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis.
  
  
  BACKGROUND
  National Institute of Neurological Disorders and Stroke (NINDS) and others.
authors.affiliation: Mallinckrodt Institute of Radiology and the Departments of Neurology and Neurosurgery, Washington University School of Medicine, St Louis, MO, USA. Electronic address: derdeync@wustl.edu.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Derdeyn
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Marc I
authors.initials: MI
authors.lastname: Chimowitz
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public, Health, Atlanta, GA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lynn
authors.affiliation: Department of Neurosurgery, State University of New York, Stony Brook, NY, USA.
authors.forename: David
authors.initials: D
authors.lastname: Fiorella
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Turan
authors.affiliation: National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD, USA.
authors.forename: L Scott
authors.initials: LS
authors.lastname: Janis
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public, Health, Atlanta, GA, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Montgomery
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public, Health, Atlanta, GA, USA.
authors.forename: Azhar
authors.initials: A
authors.lastname: Nizam
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public, Health, Atlanta, GA, USA.
authors.forename: Bethany F
authors.initials: BF
authors.lastname: Lane
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Helmi L
authors.initials: HL
authors.lastname: Lutsep
authors.affiliation: Department of Neurological Surgery and the Dotter Interventional Institute, Oregon Health Sciences University, Portland, OR, USA.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Barnwell
authors.affiliation: Departments of Neurology and Neuroscience, University of Florida, Gainesville, FL, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Waters
authors.affiliation: Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hoh
authors.affiliation: Dent Neurological Institute, Buffalo, NY, USA.
authors.forename: J Maurice
authors.initials: JM
authors.lastname: Hourihane
authors.affiliation: Department of Neurosurgery, University of Buffalo, NY, USA.
authors.forename: Elad I
authors.initials: EI
authors.lastname: Levy
authors.affiliation: Department of Neurology, University of Alabama, Birmingham, AL, USA.
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
authors.affiliation: Department of Neurosurgery, University of Alabama, Birmingham, AL, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Harrigan
authors.affiliation: Department of Neurology, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chiu
authors.affiliation: Department of Radiology, Houston Methodist Hospital, Houston, TX, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Klucznik
authors.affiliation: Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
authors.forename: Joni M
authors.initials: JM
authors.lastname: Clark
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA.
authors.forename: Cameron G
authors.initials: CG
authors.lastname: McDougall
authors.affiliation: Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Departments of Radiology and Neurosurgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: G Lee
authors.initials: GL
authors.lastname: Pride
authors.affiliation: Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Lynch
authors.affiliation: Departments of Neurology, Radiology, and Neurosurgery, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Osama O
authors.initials: OO
authors.lastname: Zaidat
authors.affiliation: Department of Radiology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Rumboldt
authors.affiliation: Department of Radiology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Cloft
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017130:Angioplasty / Q000009:adverse effects / Q000379:methods*; D001241:Aspirin / Q000627:therapeutic use; D016893:Carotid Stenosis / Q000150:complications / Q000628:therapy; D000077144:Clopidogrel; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000150:complications / Q000628:therapy*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention; D016037:Single-Blind Method; D015607:Stents; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin