This analysis piece in the BMJ looks into the evidence supporting the recommendations for thrombolysis with alteplase in the 3 to 4.5 hour window following ischaemic stroke.
They identify limited direct evidence for this group, consisting of 2 trials ECASS-III and IST-3, as well as a meta-analysis of individual patient data from other stroke thrombolysis trials.
The evidence on the effects of alteplase at 3-4.5 hours after stroke on functional outcomes is inconsistent. Some data support an increase in good functional outcome at three months, and others show a worse functional outcome at six months; any single estimate of effect from currently available data is therefore likely to be unreliable. However, data from the same trials show a clear increase in the risks of symptomatic intracranial haemorrhage and fatal intracranial haemorrhage and suggest an increase in mortality at 90 days
Unless and until there are data showing unequivocal benefits to outweigh known harms, we believe that there should not be any strong recommendation or encouragement for use of alteplase beyond three hours after stroke.
Worth the Read
It's hard to further summarise the already summarised summary, so it's probably best just to read it yourself: