title: Impact of time to treatment on tissue-type plasminogen activator-induced recanalization in acute ischemic stroke.
abstract: OBJECTIVE
  Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke.
  
  
  METHODS
  Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point.
  
  
  RESULTS
  Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >270 minutes. Recanalization occurred in 36.1% of patients. There was no linear association between time to treatment and time to recanalization, but sequential analysis showed that patients treated >270 minutes had a lower recanalization rate. Lower National Institutes of Health Stroke Scale score on admission (odds ratio [OR], 0.305; 95% confidence interval [CI], 0.1-0.933) and time to treatment ≤270 minutes (OR, 0.995; 95% CI, 0.99-0.999) emerged as independent predictors of recanalization. In patients with proximal occlusion, 41.8% recanalized. Time to treatment >90 minutes was associated with lower recanalization rate. However, only younger age (OR, 0.975; 95% CI, 0.952-0.999) and lower baseline National Institutes of Health Stroke Scale score (OR, 0.921; 95% CI, 0.855-0.993) independently predicted recanalization. In distal occlusion patients, male sex was the only independent predictor of recanalization (OR, 0.416; 95% CI, 0.195-0.887). None recanalized >270 minutes.
  
  
  CONCLUSIONS
  The effect of tPA on recanalization may decrease over time. Treatment >270 minutes predicted lack of recanalization, especially in distal occlusions.
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Muchada
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Rodriguez-Luna
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pagola
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Alan
authors.initials: A
authors.lastname: Flores
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Sanjuan
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Meler
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Boned
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Alvarez-Sabin
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Ribo
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.affiliation: From the Stroke Unit, Department of Neurology, Vall d'Hebron University Hospital Barcelona, Spain; Vall d'Hebron Research Institute, Barcelona, Spain; and Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain. mrubifu@hotmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Rubiera
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D061665:Time-to-Treatment; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D010959:Tissue Plasminogen Activator
keywords: stroke; time-to-treatment; tissue-type plasminogen activator