What is the preferred approach between intravenous (IV) thrombolysis using alteplase (tissue plasminogen activator) and intraarterial thrombolysis for treating acute ischemic stroke?

Intravenous Thrombolysis vs. Intraarterial Thrombolysis for Acute Ischemic Stroke

Intravenous (IV) thrombolysis with alteplase should be the first-line treatment for eligible patients with acute ischemic stroke, initiated as soon as possible within the treatment window, while intraarterial thrombolysis should be reserved for specific scenarios such as rescue therapy when IV thrombolysis fails to achieve recanalization. 1

Standard Treatment Approach

IV Thrombolysis (First-Line Therapy)

• IV alteplase (0.9 mg/kg, maximum dose 90 mg over 60 minutes with initial 10% as bolus over 1 minute) is recommended for eligible patients within 4.5 hours of symptom onset or last known well 1
• Treatment should be initiated as quickly as possible as outcomes are strongly time-dependent 2
• Only blood glucose assessment must precede IV alteplase administration 1
• Patients with acute hypertension should have blood pressure lowered below 185/110 mmHg before initiating IV thrombolysis 1, 2
• Extended window (3-4.5 hours) has additional exclusion criteria: age >80 years, oral anticoagulant use regardless of INR, NIHSS >25, or history of both stroke and diabetes 1

Intraarterial Thrombolysis Considerations

• Intraarterial thrombolysis may be considered as rescue therapy when early recanalization with IV thrombolysis is not achieved 1
• Particularly applicable for strokes with large clot burden (proximal middle cerebral artery, carotid terminus, basilar artery occlusions) 1
• Provides higher rates of recanalization compared to IV thrombolysis alone 1
• In the PROACT II trial with intraarterial prourokinase, patients with baseline glucose >11.1 mmol/L experienced a 36% risk of symptomatic intracranial hemorrhage 1

Combined Approach

• Eligible patients should receive IV thrombolysis even if mechanical thrombectomy is being considered 1
• Do NOT evaluate responses to IV thrombolysis before proceeding with catheter angiography for mechanical thrombectomy 1
• Combined IV and intraarterial approach may be beneficial for patients with large vessel occlusions 1
• The Interventional Management of Stroke (IMS) study showed that patients receiving reduced-dose IV alteplase (0.6 mg/kg) followed by intraarterial alteplase had better outcomes than historical placebo controls 1
• Symptomatic intracerebral hemorrhage rates were similar between combined therapy (6.3%) and standard IV rtPA (6.6%) 1

Special Considerations

• Hyperglycemia significantly increases risk of hemorrhagic complications with both IV and intraarterial thrombolysis 1
• Blood glucose levels >11.1 mmol/L are associated with substantially increased risk of symptomatic intracerebral hemorrhage 1
• Patients with clinically suspected large vessel occlusion (LVO) should have non-invasive angiography (e.g., CTA) 1
• For patients with LVO in the anterior circulation within 6-24 hours of last known well, advanced imaging (CTP or DW-MRI) should determine eligibility for mechanical thrombectomy 1

Efficacy and Safety Considerations

• IV alteplase improves functional outcomes without increasing mortality, though it carries risk of intracerebral hemorrhage 3, 4
• IV alteplase is weakly effective in recanalizing major intracranial artery occlusions 3
• Low-dose alteplase (0.6 mg/kg) showed fewer symptomatic hemorrhages compared to standard dose (0.9 mg/kg) but did not meet non-inferiority criteria for efficacy 5
• Intraarterial approaches provide higher recanalization rates but require specialized centers with neurointerventional capabilities 1

Algorithm for Decision-Making

1. For all acute ischemic stroke patients presenting within 4.5 hours of symptom onset:

   • Administer IV alteplase if eligible (no contraindications) 1
   • Do not delay IV thrombolysis to assess for mechanical thrombectomy eligibility 1

2. For patients with suspected large vessel occlusion:

   • Obtain non-invasive angiography (CTA) 1
   • If LVO confirmed, proceed with mechanical thrombectomy evaluation without waiting to assess IV thrombolysis response 1

3. If recanalization is not achieved with IV thrombolysis:

   • Consider rescue intraarterial thrombolysis in specialized centers 1
   • This is especially important for large clot burden in proximal vessels 1

4. For patients presenting beyond 4.5 hours or with wake-up stroke:

   • Advanced imaging (DWI-FLAIR mismatch or CT/MRI perfusion) can identify candidates for extended window IV thrombolysis 1
   • Mechanical thrombectomy should be considered for eligible patients with LVO up to 24 hours 1