What is the recommended treatment for acute ischemic stroke using thrombolysis with tissue plasminogen activator (tPA)?

Thrombolysis for Acute Ischemic Stroke

For acute ischemic stroke, IV recombinant tissue plasminogen activator (r-tPA) is strongly recommended if treatment can be initiated within 3 hours of symptom onset (Grade 1A evidence), with a weaker recommendation for treatment between 3-4.5 hours after onset (Grade 2C evidence). 1

Primary Treatment Recommendations

Time-Based Treatment Algorithm

• IV r-tPA (0.9 mg/kg, maximum dose 90 mg) is the recommended first-line treatment for eligible patients with acute ischemic stroke 1
• Treatment timing windows:
  • 0-3 hours: Strongly recommended (Grade 1A evidence) 1, 2
  • 3-4.5 hours: Suggested but with lower level of evidence (Grade 2C evidence) 1, 3
  • Beyond 4.5 hours: Not recommended (Grade 1B evidence) 1, 4

Alternative Approaches

• For patients with proximal cerebral artery occlusions who are ineligible for IV r-tPA, intraarterial (IA) r-tPA is suggested if treatment can be initiated within 6 hours of symptom onset (Grade 2C) 1
• IV r-tPA alone is preferred over combination IV/IA r-tPA (Grade 2C) 1
• Mechanical thrombectomy is generally not recommended (Grade 2C), though carefully selected patients may benefit 1

Efficacy and Safety Considerations

Efficacy Evidence

• Treatment within 3 hours:

  • Strong evidence shows improved clinical outcomes at 3 months 2
  • Patients treated with r-tPA are at least 30% more likely to have minimal or no disability at 3 months 2

• Treatment between 3-4.5 hours:

  • Moderate evidence shows improved outcomes (52.4% favorable outcome with alteplase vs. 45.2% with placebo) 3
  • Meta-analysis confirms benefit in this extended time window (odds ratio 1.31 for favorable outcome) 5

Safety Considerations

• Risk of symptomatic intracerebral hemorrhage:

  • Within 3 hours: 6.4% with r-tPA vs. 0.6% with placebo 2
  • 3-4.5 hours: 2.4% with alteplase vs. 0.2% with placebo 3
  • Beyond 5 hours: Significantly increased risk without proven benefit 4

• Mortality:

  • No significant difference in mortality between r-tPA and placebo when used within appropriate time windows 3, 5

Adjunctive Treatments

• Early aspirin therapy (160-325 mg) is recommended within 48 hours of stroke onset (Grade 1A) 1
• For patients with restricted mobility:
  • Prophylactic-dose subcutaneous heparin (preferably LMWH) or intermittent pneumatic compression devices are suggested (Grade 2B) 1
  • LMWH is preferred over unfractionated heparin (Grade 2B) 1
  • Elastic compression stockings are not recommended (Grade 2B) 1

Common Pitfalls and Practical Considerations

• Time is critical - delays in treatment significantly reduce effectiveness 1, 6

• Key time metrics to monitor:

  • Stroke onset to emergency department arrival (target <60 minutes) 6
  • Emergency department arrival to CT scan (target <40 minutes) 6
  • CT scan to treatment administration (target <60 minutes) 6

• Patient selection is crucial to minimize hemorrhagic complications:

  • Exclude patients with evidence of intracranial hemorrhage on imaging 1
  • Carefully assess for contraindications to thrombolysis 1
  • Consider risk factors for hemorrhagic transformation 1

• Implementation challenges:

  • In real-world practice, only a small percentage of stroke patients receive r-tPA (6% at university hospitals, 1.1% at community hospitals in one study) 6
  • Establishing efficient stroke protocols can improve treatment rates and outcomes 6