title: Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials.
abstract: OBJECTIVE
  To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice.
  
  
  METHODS
  A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany.
  
  
  METHODS
  All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants.
  
  
  METHODS
  Data from 84,439 patients with acute ischaemic stroke were analysed, 10,263 (12%) were treated with thrombolytic therapy and 74,176 (88%) were not treated.
  
  
  METHODS
  Primary endpoint was the dichotomised score on a modified Rankin scale at discharge ("favourable outcome" score 0 or 1 or "unfavourable outcome" score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis).
  
  
  RESULTS
  After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92).
  
  
  CONCLUSIONS
  The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy.
authors.affiliation: Department of Neurology Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gumbinger
authors.affiliation: Department of Neurology Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Reuter
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stock
authors.affiliation: Department of Neurology Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Tamara
authors.initials: T
authors.lastname: Sauer
authors.affiliation: 70376 Stuttgart, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Wiethölter
authors.affiliation: Office for Quality Assurance in Hospitals (GeQiK) Stuttgart at Baden-Wuerttembergische Hospital Federation, 70191 Stuttgart, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Bruder
authors.affiliation: Office for Quality Assurance in Hospitals (GeQiK) Stuttgart at Baden-Wuerttembergische Hospital Federation, 70191 Stuttgart, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rode
authors.affiliation: Department of Neurology Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kern
authors.affiliation: Department of Neurology Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Ringleb
authors.affiliation: Department of Neurology Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hennerici
authors.affiliation: Department of Neurology Heidelberg, University of Heidelberg, 69120 Heidelberg, Germany werner.hacke@med.uni-heidelberg.de.
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000401:mortality; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005858:Germany; D017052:Hospital Mortality; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D011785:Quality Assurance, Health Care; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D061665:Time-to-Treatment; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator