title: Analysis of the National Institute of Neurological Disorders and Stroke tissue plasminogen activator studies following European Cooperative Acute Stroke Study III patient selection criteria.
abstract: BACKGROUND
  In 1995 two studies by the National Institute of Neurological Disorders and Stroke (NINDS) proved that intravenous tissue plasminogen activator (t-PA) was superior to placebo in patients with stroke of less than 3 hours' duration. The recently published European Cooperative Acute Stroke Study (ECASS) III introduced new patient selection criteria and treatment between 3 and 4.5 hours. Using these criteria, t-PA was shown effective at the later time window. Both analyses used the 3-month modified Rankin scale (mRS) score as main primary outcome. We sought to study the effect of applying the ECASS III selection criteria to the original NINDS cohort.
  
  
  METHODS
  We analyzed the subgroup of patients from NINDS sample who matched the ECASSS III criteria. We examined 3-month outcomes adjusted and unadjusted for confounding factors.
  
  
  RESULTS
  The NINDS t-PA study included 624 patients. A total of 200 in the t-PA-treated group and 199 in the placebo group were selected after applying ECASS III criteria. Of these selected patients, 52% in the t-PA group versus 31% had mRS score of 0 or 1 at 3 months (P < .001). The unadjusted odds ratio for t-PA treatment versus placebo on day-90 mRS score 0 to 1 versus 2 to 6 was 2.45 (95% confidence interval: 1.63-3.69). When adjusted for baseline National Institutes of Health Stroke Scale score, smoking status, time to treatment, and history of hypertension, the odds ratio was 2.14 (95% confidence interval: 1.34-3.41) (P < .001).
  
  
  CONCLUSIONS
  Using the ECASS III criteria in patients treated in less than 3 hours, 52% of t-PA-treated patients had a favorable outcome at 3 months.
authors.affiliation: Department of Neuroscience, University of California, San Diego, San Diego, CA 92103-8466, USA. themmen@ucsd.edu
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hemmen
authors.forename: Karen S
authors.initials: KS
authors.lastname: Rapp
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Emond
authors.forename: Rema
authors.initials: R
authors.lastname: Raman
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Lyden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D016017:Odds Ratio; D020521:Stroke / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome; D014481:United States
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
references.citation: JAMA. 1995 Oct 4;274(13):1017-25
references.pmid: 7563451
references.citation: Neurology. 2001 Aug 14;57(3):474-80
references.pmid: 11502916
references.citation: Lancet. 1995 Dec 9;346(8989):1509-14
references.pmid: 7491044
references.citation: J Stroke Cerebrovasc Dis. 2009 Jan;18(1):78-9
references.pmid: 19110151
references.citation: N Engl J Med. 2008 Sep 25;359(13):1393-5
references.pmid: 18815401
references.citation: N Engl J Med. 1995 Dec 14;333(24):1581-7
references.pmid: 7477192
references.citation: Lancet. 1995 Jan 7;345(8941):57
references.pmid: 7799716
references.citation: Lancet. 1998 Oct 17;352(9136):1245-51
references.pmid: 9788453
references.citation: N Engl J Med. 2008 Sep 25;359(13):1317-29
references.pmid: 18815396
references.citation: JAMA. 1996 Sep 25;276(12):961-6
references.pmid: 8805730
references.citation: Lancet Neurol. 2009 Feb;8(2):141-50
references.pmid: 19097942
references.citation: Age Ageing. 2006 Nov;35(6):572-80
references.pmid: 17047006
references.citation: JAMA. 1999 Dec 1;282(21):2019-26
references.pmid: 10591384