Thrombolytic Therapy During The Early ‘90s: Part 1

The early ‘90s witnessed the rise of thrombolytic RCTs for acute ischemic stroke. This article focuses on the impact of these trials on the development of the tPA time window for acute ischemic stroke treatment.


The first tPA trial was a double-blinded RCT of acute ischemic stroke sufferers presenting within six hours of the onset of symptoms. Data analysis was conducted through modified intention to treat and intention-to-treat strategies.

There was a clinically relevant improvement in patients who took tPA, but it was not statistically significant. However, the modified analysis saw statistical significance in the functional independence improvement.


This well-known stroke trial examined the results after patients took tPA within a three-hour window of the onset of symptoms. There was a statistically significant absolute difference in no or minimal disability favoring tPA. This is considered the impetus for the original 3-hour time window.


The RCT examined patients who presented between 0-3 hours and 3-6 hours. It dichotomized patients to poor (mRS 2-6) or excellent (mRS 0-1) outcomes. This grouping among stroke patients proved optimistic. tPA recipients saw a non-significant benefit.

Upon reexamination of the data using different standards for dichotomization, tPA recipients witnessed a statistically significant benefit of 8.3%.

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