Stroke: tissue plasminogen activator had no clear effect.

Clinical bottom line (level 1b-)

  1. Patients with acute ischaemic stroke who were given tissue plasminogen activator had no clear difference in favourable outcome, than those given placebo.
  2. Patients who were given tissue plasminogen activator had no clear difference in death, than those given placebo.
Kwiatkowski et al: New England Journal of Medicine 1999; 340: 1781-1787
Expires December 2002

The study

Double-blinded ?concealed randomised trial with intention-to-treat
Setting: multicentre, USA

624 patients (aged ?, ?% male) acute ischaemic stroke and able to be treated within three hours after onset of symptoms, and with a measurable neurologic deficit according to the National Institutes of Health Stroke Scale
Note:
  • Randomisation was stratified according to the time since onset of the stroke (about half were enrolled within 90 minutes of symptom onset) and the clinical centre


    • Control Group: (n = 312, 312 analysed): placebo
    Experimental Group: (n = 312, 312 analysed): tissue plasminogen activator

    96% followed for 12 months
    Outcome notes:
    • favourable outcome with Barthel Index : minimal or no disability- scores of 95 or 100 on the Barthel Index
    • favourable outcome on modified Rankin scale : minimal or no disability- score of 0 or 1
    • favourable outcome on Glasgow Outcome Scale : minimal or no disability- score of 1

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    favourable outcome with Barthel Index 12 months 38
    (12.2%)    		 50
    (16.0%)    		 4.00%
    (-2% to 10%)    		 3.85%
    (-1.61% to 9.30%)    		 26
    (NNT = 11 to infinity;
    NNH = 62 to infinity)
    favourable outcome on modified Rankin scale 12 months 28
    (8.97%)    		 41
    (13.1%)    		 5.00%
    (-1.00% to 10%)    		 4.17%
    (-0.74% to 9.08%)    		 24
    (NNT = 11 to infinity;
    NNH = 134 to infinity)
    favourable outcome on Glasgow Outcome Scale 12 months 32
    (10.3%)    		 43
    (13.8%)    		 4.00%
    (-2.00% to 9.00%)    		 3.53%
    (-1.57% to 8.62%)    		 28
    (NNT = 12 to infinity;
    NNH = 64 to infinity)
    total death 12 months 87
    (27.9%)    		 76
    (24.4%)    		 13.0%
    (-14.0% to 33.0%)    		 3.53%
    (-3.36% to 10.4%)    		 28
    (NNT = 10 to infinity;
    NNH = 30 to infinity)
    cerebrovascular death 12 months 26
    (8.33%)    		 28
    (8.97%)    		 -8.00%
    (-79.0% to 35.0%)    		 -0.64%
    (-5.05% to 3.77%)    		 -156
    (NNT = 27 to infinity;
    NNH = 20 to infinity)
    cardiovascular death 12 months 39
    (12.5%)    		 28
    (8.97%)    		 28.0%
    (-14.0% to 55.0%)    		 3.53%
    (-1.32% to 8.38%)    		 28
    (NNT = 12 to infinity;
    NNH = 75 to infinity)

    Citation

    1. Kwiatkowski TG, Libman RB, Frankel M, et al: Effects of tissue plasminogen activator for acute ischemic stroke at one year. New England Journal of Medicine 1999; 340: 1781-1787
    Contributor: Clare Wotton and Musab Hayatli, December 1999
    Reviewer:

    Clinical Question.
    Patient acute ischaemic stroke
    Intervention or Exposure tissue plasminogen activator
    Comparison placebo
    Outcome minimal or no disability