Is there any benefit from thrombolysis in an extended time window in patients with acute ischemic stroke? Critical appraisal of IST-3 study (The Third International Stroke Study)

Vasileios Papavasileiou, George Ntaios, Konstantinos Makaritsis, Kostas Vemmos, Haralampos Milionis



Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke (AIS) is an established and effective evidence-based therapy that improves long-term functional outcome. According to current international guidelines, intravenous rt-PA can be administered up to 4.5 hours after the onset of symptoms. IST-3 (Third International Stroke Study), the largest study of intravenous thrombolysis in AIS, had a negative primary outcome (significantly improved dichotomized Oxford Handicap Score at six-months). However, based mainly on the positive secondary ordinal shift analysis, the IST-3 collaborative group presents the study as one with a positive outcome. Moreover, the controversial design of IST-3 flares the debate on whether the interpretation of the findings of the study is the one presented by the researchers or the one supported by the various study censurers. Herein, we present a critical appraisal of the study in order to explore whether its results can promote any changes with regard to the standard treatment of patients with AIS.