What are the benefits of thrombolysis with alteplase (tissue plasminogen activator) in patients with acute ischemic stroke?

Benefits of Thrombolysis with Alteplase in Acute Ischemic Stroke

Intravenous alteplase (tPA) significantly improves functional outcomes and reduces disability when administered within 4.5 hours of stroke symptom onset, with greatest benefits seen when given as early as possible. 1

Time Windows and Efficacy

• 0-3 hour window: Strongest recommendation (Class I, Level A) with greatest benefit-to-risk ratio 1

  • 52.4% of patients achieve favorable outcomes (modified Rankin Scale 0-1) with alteplase versus 45.2% with placebo (odds ratio 1.34) 2

• 3-4.5 hour window: Still recommended (Class I, Level B) but with additional exclusion criteria 3, 1

  • Significant improvement in clinical outcomes compared to placebo
  • Global analysis shows improved outcomes (odds ratio 1.28) 2

• Extended windows (4.5-9 hours): May be beneficial in select patients with CT or MRI core/perfusion mismatch 1

  • Wake-up strokes may benefit if MRI shows DWI-FLAIR mismatch 1

Mortality and Functional Outcomes

• No significant difference in 90-day mortality between alteplase and placebo (7.7% vs 8.4%) 2
• Improved distribution of modified Rankin Scale scores across all categories 2
• Benefits seen across stroke severity ranges, including mild strokes that may still be disabling 3, 1
• Patients with preexisting disability may still benefit from treatment 3

Risk of Hemorrhagic Complications

• Symptomatic intracerebral hemorrhage (SICH) occurs in approximately 2.4% of treated patients versus 0.2% with placebo 2
• Risk of SICH is higher with standard dose (0.9 mg/kg) compared to lower doses (2.1% vs 1.0%) 4
• However, standard dose (0.9 mg/kg) remains recommended as it has proven efficacy in improving functional outcomes 3, 1

Special Considerations

• Vertebrobasilar (brainstem) strokes have high mortality (>80%) without treatment, making thrombolysis particularly important 1
• Patients with seizure at stroke onset can benefit if evidence suggests residual impairments are due to stroke rather than postictal phenomena 3
• Early improvement that still leaves moderate impairment is not a reason to withhold treatment 3
• Patients >80 years of age can safely receive treatment in the 3-4.5 hour window 3

Administration Protocol

• Dose: 0.9 mg/kg (maximum 90 mg) 3, 1
• Administration: 10% as bolus, remaining 90% as infusion over 60 minutes 3
• Pre-treatment requirements: Blood pressure <185/110 mmHg, blood glucose assessment, neuroimaging to exclude hemorrhage 1

Important Caveats

• Time is critical - earlier treatment leads to better outcomes 1
• Delaying treatment for additional tests beyond necessary neuroimaging should be avoided 1
• Excluding patients with mild but potentially disabling deficits is not recommended 1
• For patients eligible for both intravenous alteplase and endovascular thrombectomy (EVT), both treatments should be administered, with alteplase initiated while preparing for EVT 3

When consenting patients for thrombolysis, emphasize that treatment offers the best chance of achieving functional independence and reducing disability, with benefits far outweighing the risks for eligible patients when administered within the appropriate time window.