Published online by Cambridge University Press: 26 August 2009
The landmark NINDS IV tPA trial showed that treatment with tPA within 3 hours of symptom onset improved neurologic impairment and functional outcome. Despite an increase in symptomatic hemorrhages from 0.6% in the placebo treated group to 6.4% in the active treatment group, mortality was not increased and functional outcome improved, even among patients with the most severe strokes.
The NINDS trial was subsequently criticized because it subjected some patient groups who were assumed to be unlikely to benefit from thrombolytic agents to a potentially harmful treatment. For instance, patients with proximal ICA-occlusions are unlikely to benefit from IV-tPA. Similarly, it has been suggested that patients with small, deep infarcts should not receive thrombolytics because of the generally favourable outcome and the presumed different pathological processes underlying small vessel occlusions.
In the NINDS trial, no patient subgroups could be identified that appeared not to benefit from tPA. However, in this trial stroke subtype was established based on clinical impression. Many studies suggest that the identification of stroke subtypes cannot be made reliably on clinical criteria and early CT alone.
In the NINDS trial, the only factor that appeared to improve the favourable response to tPA was the time between symptom onset and treatment.