ECASS III

Population

• Patients with acute ischemic stroke treated between 3 and 4.5 hours after onset, after CT exclusion of brain hemorrhage or major infarction.

Intervention

Intravenous alteplase 0.9 mg per kilogram.

Comparator

Placebo.

Key results

• Favorable outcome occurred in 52.4% with alteplase vs 45.2% with placebo (OR 1.34; 95% CI 1.02-1.76; p=0.04).
• The global outcome analysis also favored alteplase (OR 1.28; 95% CI 1.00-1.65; p<0.05).
• Median time to alteplase was 3 hours 59 minutes.
• Mortality was 7.7% with alteplase and 8.4% with placebo (p=0.68).

Harms

• Any intracranial hemorrhage was more common with alteplase than placebo (27.0% vs 17.6%; p=0.001).
• Symptomatic intracranial hemorrhage occurred in 2.4% with alteplase vs 0.2% with placebo (p=0.008).
• Other serious adverse events did not differ significantly.

Practice impact

• Eligible patients presenting between 3 and 4.5 hours should still be considered for intravenous alteplase after CT exclusion of hemorrhage and large infarction.

Applicability

• Most applicable to acute ischemic stroke without CT hemorrhage or major infarction when treatment can start between 3 and 4.5 hours after onset.

Limitations

• The trial tested a 3-to-4.5-hour window after CT screening, not an open-ended late window.
• Benefit was disability, not survival; mortality did not differ.
• Alteplase increased symptomatic intracranial hemorrhage.

Common misinterpretations

• ECASS III does not make alteplase hemorrhage-free; symptomatic intracranial hemorrhage was more frequent.
• This is not a license to treat beyond 4.5 hours without additional selection.