Time Window for Thrombolysis in Acute Ischemic Stroke
Intravenous tPA should be administered within 3 hours of stroke symptom onset as the primary treatment window, with an extended window of 3-4.5 hours available for carefully selected patients who meet additional exclusion criteria. 1, 2
Standard Treatment Window (0-3 Hours)
The 0-3 hour window represents the strongest evidence for benefit, with high-quality data showing that tPA increases the likelihood of good functional outcome (154 more excellent outcomes per 1,000 patients treated) with no increase in overall mortality. 1, 2
The dose is 0.9 mg/kg (maximum 90 mg), with 10% given as initial bolus and remainder infused over 1 hour. 1
Symptomatic intracranial hemorrhage occurs in approximately 7.9% of tPA-treated patients versus 3.5% in placebo patients within this window. 1
Earlier treatment within the 3-hour window produces superior outcomes - delays should be minimized with a target door-to-needle time of 30 minutes (median), with 90th percentile at 60 minutes. 1, 2
Extended Treatment Window (3-4.5 Hours)
The 3-4.5 hour window is supported by high-quality evidence (Class I Recommendation, Level B) but shows smaller treatment effect than the 0-3 hour window (69 more favorable events per 1,000 patients versus 154 per 1,000 in the earlier window). 1, 2
The ECASS-3 trial demonstrated that 52.4% of tPA-treated patients achieved excellent outcome (mRS 0-1) versus 45.2% with placebo in this extended window. 1, 2
Additional Exclusion Criteria for 3-4.5 Hour Window
The following patients must be excluded from treatment in the 3-4.5 hour window (but may be eligible in the 0-3 hour window): 1, 2
- Age >80 years
- Patients taking oral anticoagulants
- Baseline NIHSS score >25
- Combination of previous stroke AND diabetes mellitus
Beyond 4.5 Hours
IV tPA should NOT be administered beyond 4.5 hours based on lack of proven benefit and potential harm. 3
For patients presenting 4.5-6 hours after onset, treatment should focus on aspirin 160-325 mg within 48 hours and supportive care including VTE prophylaxis. 3
Intra-arterial thrombolysis may be considered for proximal cerebral artery occlusions within 6 hours in select cases, though this represents a different treatment modality. 1, 3
Critical Safety Considerations
Symptomatic ICH risk increases with delayed treatment: 2.4% (ECASS-3 definition) to 7.9% (NINDS definition) in the 3-4.5 hour window for tPA-treated patients. 1
Fatal ICH occurs significantly more often with thrombolytic therapy across all time-to-treatment strata up to 6 hours (OR 3.70,95% CI 2.36-5.79), with absolute risks of 3.5% with tPA versus 0.8% with placebo. 1
Real-world implementation data from SITS-MOST showed symptomatic ICH rates of 7.3% in routine clinical practice, comparable to randomized trial results. 1
Key Clinical Pitfalls to Avoid
Do not delay treatment to wait for the extended window - approximately 45% of patients treated in the 3-4.5 hour window in registry data actually arrived within 2 hours of symptom onset and could have been treated earlier. 4
Do not use tPA beyond 4.5 hours in routine practice - the evidence shows harm without benefit in this timeframe. 3
Do not forget the additional exclusion criteria when treating in the 3-4.5 hour window - protocol violations in ECASS-I resulted in 42% mortality in those who received tPA inappropriately. 1