What is the tPA (tissue plasminogen activator) window for ischemic stroke?

tPA Window for Ischemic Stroke

The standard window for intravenous tPA administration in acute ischemic stroke is within 3 hours of symptom onset, with an extended window of 3-4.5 hours for carefully selected patients who meet specific criteria. 1, 2

Standard 0-3 Hour Window

• IV tPA should be offered to acute ischemic stroke patients who meet National Institute of Neurological Disorders and Stroke (NINDS) inclusion/exclusion criteria and can be treated within 3 hours after symptom onset 1
• Treatment within this window increases the probability of better long-term functional outcomes with a Number Needed to Treat (NNT) of 8 (95% CI 4 to 31) 1
• Earlier treatment within this window is associated with better outcomes, as the opportunity for improvement is greater with earlier treatment 2
• The risk of symptomatic intracerebral hemorrhage (sICH) within 36 hours is approximately 6.4% with tPA versus 0.6% with placebo in the 0-3 hour window 3

Extended 3-4.5 Hour Window

• IV tPA should be considered in acute ischemic stroke patients who meet European Cooperative Acute Stroke Study (ECASS) III inclusion/exclusion criteria and can be treated between 3-4.5 hours after symptom onset 1

• The extended window has additional exclusion criteria beyond the standard 0-3 hour window 1:

  • Patients older than 80 years
  • Those taking oral anticoagulants with an international normalized ratio ≤1.7
  • Those with a baseline National Institutes of Health Stroke Scale score >25
  • Those with both a history of stroke and diabetes

• Treatment in the 3-4.5 hour window has a lower efficacy with NNT of 14 (95% CI 7 to 244) 1

• The risk of sICH is higher in the extended window, with rates of 7.9% in tPA-treated patients versus 3.5% in placebo patients 2

Clinical Implementation

• Despite FDA approval only for the 0-3 hour window, the American Heart Association/American Stroke Association provides a Class I Recommendation, Level of Evidence B for the extended 3-4.5 hour window 1, 2
• Once the decision is made to administer IV tPA within either time window, treatment should be initiated as rapidly as possible 1
• The effectiveness of tPA has been less well established in institutions without systems in place to safely administer the medication 1
• Community implementation studies have shown similar safety and efficacy outcomes between the standard and extended windows when protocols are properly followed 4

Shared Decision-Making

• When feasible, shared decision-making between the patient (or surrogate) and healthcare team should include discussion of potential benefits and harms prior to tPA administration 1
• Patients tend to overestimate benefits and underestimate harms associated with sICH 1
• The risk-benefit ratio changes over time, with benefits of reperfusion outweighing risks of complications within the approved window periods 2

Common Pitfalls

• Delaying treatment within the window period reduces chances of good outcomes 2
• Administering tPA outside the recommended time windows significantly increases bleeding risk without established benefit 5
• Failing to recognize contraindications specific to the extended time window 1
• Not considering that mortality at three months is not significantly different between tPA and placebo groups (17% vs 21%, p=0.30) despite the functional benefits 3