From the Guidelines

Administration of Recombinant Tissue Plasminogen Activator (rtPA) within 3 hours of stroke onset is appropriate.

The use of intravenous rtPA is associated with improved outcomes for patients with acute ischemic stroke who can be treated within 3 hours of the last known well time before symptom onset 1.
Earlier treatment is more likely to result in a favorable outcome, with a significant increase in favorable outcome in patients treated with intravenous rtPA within 1.5 hours of symptom onset 1.
The dosing regimen for rtPA is 0.9 mg/kg (maximum of 90 mg), with 10% given as an initial bolus and the remainder infused over 1 hour 1.
The major risk of treatment is symptomatic brain hemorrhage, which occurred in 6.4% of patients treated with rtPA and 0.6% of patients given placebo 1.
The likelihood of favorable outcome is affected by the severity of deficits and the patient’s age, with those with mild-to-moderate strokes and those younger than 75 having the greatest possibility for a favorable response to treatment 1.

Benefits: improved outcomes, increased rate of excellent outcomes, and improved outcomes along the entire range of poststroke disability 1.
Risks: increased rates of intracranial hemorrhage, which may be fatal, and symptomatic brain hemorrhage 1.

The American Heart Association/American Stroke Association recommends intravenous administration of rtPA for treatment of carefully selected patients who can receive the medication within 3 hours of onset of stroke 1.
The European Medicines Agency has expanded approval of intravenous rtPA to the 3- to 4.5-hour window, while the US FDA has declined to do so 1.

From the Research

The administration of rtPA within 3 hours of stroke onset is a widely accepted treatment for acute ischemic stroke, as it has been shown to improve outcomes in patients 2.
A meta-analysis of clinical outcomes of intravenous recombinant tissue plasminogen activator for acute ischemic stroke found that treatment within 3 hours of symptom onset may not be more beneficial than treatment between 3-4.5 hours, in terms of favorable functional outcome and mortality 3.
However, another study found that while rtPA improves outcomes for patients with acute ischemic stroke, current approved use is limited to within 3 hours of symptom onset, and treatment beyond 3 hours may increase the risk of symptomatic intracranial hemorrhage 4.

The efficacy and safety of rtPA have been established in several studies, including the National Institutes of Neurological Disorders and Stroke (NINDS) study, which found that intravenous rtPA improves outcomes in acute ischemic stroke patients when administered within 3 hours of symptom onset 2.
A study published in the Journal of the American Medical Association (JAMA) found that rtPA does not provide a significant benefit when administered between 3 and 5 hours after symptom onset, and may increase the risk of symptomatic intracranial hemorrhage 4.
However, another study suggested that a subgroup of patients at low risk for thrombolysis-related intracranial hemorrhage may benefit from rtPA even when treated after 3 hours 5.

The therapeutic time window for rtPA administration is limited, and more than half of treated patients are not independent in the chronic stage 6.
The European Cooperative Acute Stroke Study III found that IV rtPA administered between 3 and 4.5 hours after stroke onset significantly improved clinical outcomes in stroke patients, leading to a renewal of recommendation in guidelines in Europe, Canada, and the United States 6.