ECASS III Criteria for Administering Intravenous Alteplase in Acute Ischemic Stroke
The ECASS III criteria define specific parameters for administering intravenous alteplase in the 3-4.5 hour time window after acute ischemic stroke onset, including age restrictions, stroke severity limitations, and additional exclusion criteria beyond those used for the standard 0-3 hour window. 1
Time Window and Basic Inclusion Criteria
- Treatment with IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 min with initial 10% of dose given as bolus over 1 min) is recommended for selected patients who can be treated within 3-4.5 hours of ischemic stroke symptom onset or when the patient was last known to be at baseline state 1
- Stroke symptoms must be present for at least 30 minutes without significant improvement prior to treatment 1
- Treatment should be initiated as quickly as possible within this time frame as outcomes are strongly time-dependent 1
ECASS III-Specific Exclusion Criteria (Beyond Standard 0-3 Hour Criteria)
The ECASS III trial applied additional exclusion criteria for the 3-4.5 hour window that weren't applicable to the 0-3 hour window:
- Age >80 years 1
- Severe stroke (NIHSS score >25) 1
- Any oral anticoagulant use regardless of INR or PT 1
- History of both diabetes mellitus AND prior stroke 1
- Imaging evidence of ischemic injury involving more than one-third of the middle cerebral artery territory 1
Standard Exclusion Criteria (Applicable to Both 0-3 and 3-4.5 Hour Windows)
- Unclear time of symptom onset or unwitnessed symptom onset with time last known to be at baseline state >4.5 hours 1
- Acute intracranial hemorrhage on CT scan 1
- Extensive regions of clear hypoattenuation on CT scan (representing irreversible injury) 1
- Prior ischemic stroke within 3 months 1
- Recent severe head trauma within 3 months 1
- Intracranial/spinal surgery within prior 3 months 1
- History of intracranial hemorrhage 1
- Symptoms consistent with subarachnoid hemorrhage 1
- GI malignancy or GI bleeding within 21 days 1
- Coagulopathy (platelets <100,000/mm³, INR >1.7, aPTT >40 s, or PT >15 s) 1
- Treatment dose of LMWH within previous 24 hours 1
- Direct thrombin inhibitors or factor Xa inhibitors unless laboratory tests are normal or patient has not received a dose for >48 hours (with normal renal function) 1
- Concurrent use of glycoprotein IIb/IIIa receptor inhibitors 1
- Infective endocarditis 1
- Aortic arch dissection 1
- Intra-axial intracranial neoplasm 1
Blood Pressure Requirements
- IV alteplase is recommended in patients whose BP can be lowered safely to <185/110 mmHg with antihypertensive agents 1
- The physician should assess the stability of the BP before starting IV alteplase 1
Efficacy and Safety Considerations
- The ECASS III trial demonstrated that alteplase administered between 3-4.5 hours after stroke onset improved clinical outcomes compared to placebo (52.4% vs. 45.2% favorable outcome) 2
- However, symptomatic intracranial hemorrhage was more frequent with alteplase than with placebo (2.4% vs. 0.2%) 2
- A 2020 reanalysis of ECASS III data adjusting for baseline imbalances questioned the efficacy findings, suggesting no significant benefits when controlling for baseline differences 3
- Despite this controversy, current AHA/ASA guidelines still recommend IV alteplase in the 3-4.5 hour window for eligible patients 1
Important Clinical Considerations
- For patients >80 years presenting in the 3-4.5 hour window, IV alteplase may be safe and effective despite being excluded from the original ECASS III criteria 1
- For patients with mild stroke symptoms presenting in the 3-4.5 hour window, IV alteplase may be reasonable with careful consideration of risks versus benefits 1
- Every effort should be made to treat patients as early as possible within the therapeutic window, as earlier treatment is associated with better outcomes 1, 4