Are thrombolytics (tissue plasminogen activators, tPA), such as alteplase (rtPA), effective in treating acute ischemic stroke?

Thrombolytics Are Effective in Acute Ischemic Stroke Treatment Within Specific Time Windows

Intravenous thrombolysis with alteplase (tPA) is both effective and safe for treating acute ischemic stroke when administered within appropriate time windows, significantly improving functional outcomes compared to placebo. 1

Efficacy of Thrombolytics

Time Windows for Treatment

• 0-3 hours after symptom onset: Strongest recommendation (Grade 1A) with highest efficacy 2
• 3-4.5 hours after symptom onset: Still effective but with additional exclusion criteria (Grade 2C) 2
  • Additional exclusion criteria for 3-4.5 hour window: patients >80 years, those on oral anticoagulants regardless of INR, baseline NIHSS >25, or patients with both history of stroke and diabetes 2
• Beyond 4.5 hours: Limited evidence supports use in selected patients with favorable imaging 1

Evidence of Benefit

• The ECASS-3 trial demonstrated that patients treated with alteplase between 3-4.5 hours had significantly better outcomes than those receiving placebo (52.4% vs 45.2% favorable outcomes; odds ratio 1.34) 3
• Earlier treatment leads to better outcomes, with a clear time-dependent effect on efficacy 1
• Meta-analyses of major trials confirm that thrombolysis improves functional outcomes when administered within appropriate time windows 2

Administration Protocol

Dosing and Administration

• Recommended dose: 0.9 mg/kg (maximum 90 mg) 1
• Administration method: 10% bolus over 1 minute, followed by 90% infusion over 60 minutes 1

Patient Selection Criteria

• Blood pressure must be <185/110 mmHg before treatment and maintained <180/105 mmHg after treatment 1
• No evidence of intracranial hemorrhage on initial neuroimaging 1
• Blood glucose should be evaluated and hypoglycemia (<60 mg/dL) treated before thrombolysis 1

Safety Considerations

Hemorrhagic Risk

• Symptomatic intracranial hemorrhage occurs in approximately 2.4% of patients treated with alteplase 1
• In ECASS-3, symptomatic intracranial hemorrhage was higher with alteplase than placebo (2.4% vs 0.2%), but mortality did not differ significantly (7.7% vs 8.4%) 3
• Risk of hemorrhage increases with delayed treatment, but benefits still outweigh risks within approved time windows 2

Contraindications

• Absolute contraindications include:
  • Intracranial hemorrhage on initial neuroimaging
  • Ischemic stroke within the last 3 months
  • Severe head trauma in the last 3 months
  • Unknown or unwitnessed symptom onset with last seen normal >4.5 hours
  • Active bleeding or recent major surgery 1

Alternative and Adjunctive Treatments

Mechanical Thrombectomy

• Can be considered for patients with large vessel occlusions, particularly those with contraindications to IV thrombolysis 1
• May be beneficial up to 24 hours in selected patients with favorable imaging 1

Antiplatelet Therapy

• Early aspirin therapy (160-325 mg) is recommended for patients not eligible for thrombolysis 2
• Not recommended as an alternative to thrombolysis for eligible patients within the treatment window 1

Monitoring and Follow-up

• Close neurological monitoring every 15 minutes for the first 2 hours after administration 1
• Blood pressure monitoring and management is critical to reduce hemorrhagic complications 1

Common Pitfalls to Avoid

• Delayed treatment: "Time is brain" – every minute counts in acute stroke treatment
• Rigid application of time windows: Consider individual benefit-risk profiles rather than strict cutoffs
• Overlooking contraindications: Careful patient selection is essential to minimize risks
• Inadequate blood pressure control: Failure to maintain BP targets increases hemorrhage risk
• Neglecting post-thrombolysis monitoring: Close observation is necessary to detect complications early

Thrombolytic therapy remains the cornerstone of acute ischemic stroke management, with clear evidence supporting its use within established time windows. The benefit-to-risk ratio is most favorable when treatment is initiated as early as possible after symptom onset.