When is thrombolysis with tissue plasminogen activator (tPA) indicated for acute stroke?

Thrombolysis for Acute Ischemic Stroke

IV recombinant tissue plasminogen activator (r-tPA) should be administered to patients with acute ischemic stroke within 3 hours of symptom onset if they meet NINDS inclusion/exclusion criteria, and should be considered for patients between 3-4.5 hours if they meet ECASS III criteria. 1, 2

Time Windows for Thrombolysis

• IV r-tPA is strongly recommended for patients with acute ischemic stroke when treatment can be initiated within 3 hours of symptom onset (Grade 1A evidence) 1, 2
• IV r-tPA should be considered for patients when treatment can be initiated between 3-4.5 hours after symptom onset, though with a lower level of evidence (Grade 2C) 1
• IV r-tPA is not recommended for patients when treatment cannot be initiated within 4.5 hours of symptom onset (Grade 1B) 1
• Once the decision is made to administer IV tPA, the patient should be treated as rapidly as possible 1

Dosing

• The recommended dose is 0.9 mg/kg of r-tPA (maximum dose 90 mg) 1, 2
• 10% of the total dose should be administered as a bolus and the remaining 90% infused over 60 minutes 1

Patient Selection Criteria

• Patients must meet NINDS inclusion/exclusion criteria for treatment within 3 hours 1, 2
• Patients must meet ECASS III inclusion/exclusion criteria for treatment between 3-4.5 hours 1
• Patient selection is crucial to minimize hemorrhagic complications 2
• Patients must have no evidence of intracranial hemorrhage on initial imaging 2

Contraindications and Safety Considerations

• Careful assessment for contraindications to thrombolysis is essential to minimize risk of symptomatic intracerebral hemorrhage (ICH) 2
• The risk of symptomatic ICH is significantly increased with r-tPA treatment (7.0% vs 1.1% in placebo within 3-5 hours) 3
• Fatal ICH is also increased with r-tPA treatment (3.0% vs 0.3% in placebo) 3
• Patients with major early infarct signs on initial CT scan should be excluded due to increased risk of hemorrhagic complications 4

Alternative Approaches for Ineligible Patients

• For patients with acute ischemic stroke due to proximal cerebral artery occlusions who don't meet eligibility criteria for IV r-tPA, intraarterial (IA) r-tPA may be considered if initiated within 6 hours of symptom onset (Grade 2C) 1
• IV r-tPA is suggested over combination IV/IA r-tPA (Grade 2C) 1
• Mechanical thrombectomy is generally not recommended (Grade 2C), though carefully selected patients may choose this intervention 1

Adjunctive Treatments

• Early aspirin therapy (160-325 mg) is recommended within 48 hours of stroke onset (Grade 1A) 1, 2
• For patients with restricted mobility, prophylactic-dose subcutaneous heparin (preferably LMWH) or intermittent pneumatic compression devices are suggested (Grade 2B) 1, 2
• LMWH is preferred over unfractionated heparin for DVT prophylaxis (Grade 2B) 1, 2

Efficacy Outcomes

• Treatment with r-tPA within 3 hours improves functional outcomes at 90 days 1
• The odds ratio for a favorable outcome (defined as minimal or no disability at 90 days) is 1.7 (95% CI 1.2 to 2.6) for patients treated with r-tPA compared to placebo 1
• Absolute improvement in favorable outcome (modified Rankin Scale score 0-1) is approximately 13% (39% vs 26%) 1
• No significant benefit has been demonstrated for r-tPA treatment between 3-5 hours in the ATLANTIS study 3

Institutional Considerations

• The effectiveness of tPA has been less well established in institutions without systems in place to safely administer the medication 1
• Protocols for rapid assessment, imaging, and treatment decision-making are essential for safe and effective implementation of thrombolysis 2