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Pooled Analysis of ATLANTIS, ECASS, and NINDS Trials

Summary:

  • This meta-analysis of several large clinical trials was important in showing that the earlier the initiation of tPA from the onset of symptoms the better odds of a favorable outcome.
  • The greatest chance for a favorable outcome occurs when tPA is given within 90 minutes of symptom onset.
  • This meta-analysis also contributed to the further evaluation of tPA beyond the 3 hour window time frame and contributed to the recommendations of offering treatment to those up to 4.5 hours of onset of symptoms.

Pooled Analysis of ATLANTIS, ECASS, and NINDS Trials

  • Hacke W et al. Association of outcome with early stroke treatment: pooled analysis of Atlantis, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363:768-774. PubMed
    Study Design Meta-analysis of 6 large, prospective, multicenter, randomized, clinical trials
    Sample Size N = 27,775
    Population Adult patients from > 300 hospitals and 18 countries
    Inclusion Criteria
    • NINDS Parts 1 and 2 at the 3 hour window of presentation
    • ECASS parts 1 and 2 at the 6 hour window of presentation
    • ATLANTIS trials Part A (the 6 hour window) and B (the 5 hour window)
    Exclusion Criteria
    • Preceding stroke
    • Head trauma
    • Major surgery
    • History of intracerebral hemorrhage
    • Elevated blood pressure
    • Use of anticoagulants
    • Thrombocytopenia
    • Anemia
    Interventions
    • Various doses of r-tPA
    • Placebo
    Primary Endpoint Favorable 3 month neurologic outcome as defined by a score on Modified Rankin scale of 0 or 1, Barthel Index 95 or 100, and NIHSS ( 0 or 1)
    Secondary Endpoint Intracerebral hemorrhage and death
    Results

    The odds ratios (OR) of r-tPA vs placebo based on time of treatment in relation to symptoms onset for a favorable outcome were:

    • 2.8 between 0 - 90 min
    • 1.6 between 91 - 180 min
    • 1.4 between 181 - 270 min
    • 1.2 between 271 - 360 min

    The hazards ratio (HR) for death was only significant for the 271 - 360 min group; HR 1.45

    The risk of intracerebral hemorrhage was associated with tPA use and the age, but not the timing of treatment in relation to symptom onset

    Conclusions

    There appears to be a relationship between the onset of symptoms and timing of tPA with patients presenting earlier receiving more benefit in neurologic outcome at 90 days, but not mortality.

    Comments

    This meta-analysis not only reaffirmed earlier findings that those presenting within 3 hours of symptoms onset appear to benefit, but it also contributed to the further evaluation of tPA beyond the 3 hour window time frame and contributed to the recommendations of offering treatment to those up to 4.5 hours of onset of symptoms.

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MESH Terms & Keywords

  • tPA Alteplase, Acute Ischemic Stroke, Meta Analysis Atlantis ECASS NINDS