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Earlier tissue plasminogen activator treatment improves ischemic stroke outcome, but aspects of the time-benefit relationship still not well delineated are: (1) the degree of additional benefit accrued with treatment in the first 60 minutes after onset, and (2) the shape of the time-benefit curve through 4.5 hours.

We analyzed patients who had acute ischemic stroke treated with intravenous tissue plasminogen activator within 4.5 hours of onset from the Get With The Guidelines-Stroke US national program. Onset-to-treatment time was analyzed as a continuous, potentially nonlinear variable and as a categorical variable comparing patients treated within 60 minutes of onset with later epochs.

Among 65 384 tissue plasminogen activator–treated patients, the median onset-to-treatment time was 141 minutes (interquartile range, 110–173) and 878 patients (1.3%) were treated within the first 60 …