Management of Acute Ischemic Stroke Based on Time of Presentation
Intravenous alteplase (0.9 mg/kg, maximum 90 mg) should be administered to eligible patients within 4.5 hours of symptom onset, with mechanical thrombectomy performed for large vessel occlusions within 6-24 hours based on imaging selection criteria. 1
0-3 Hour Window
IV Alteplase - Class I Recommendations
Administer IV alteplase (0.9 mg/kg, max 90 mg over 60 minutes with 10% bolus over 1 minute) to all eligible patients within 3 hours of symptom onset or last known well. 1
Treat patients of all ages ≥18 years equally, including those >80 years old. 1
Treat severe strokes (high NIHSS) within this window despite increased hemorrhagic transformation risk, as clinical benefit remains proven. 1
Pre-treatment Requirements
Blood pressure must be lowered to <185/110 mmHg before alteplase administration and maintained <180/105 mmHg for 24 hours post-treatment. 1, 2
Blood glucose >50 mg/dL is required; patients with glucose <50 or >400 mg/dL should be normalized first. 1
CT or MRI must exclude hemorrhage; mild-to-moderate early ischemic changes are acceptable (not frank hypodensity). 1
Specific Populations
Patients on antiplatelet monotherapy or dual antiplatelet therapy (aspirin + clopidogrel) should receive alteplase despite slightly increased hemorrhagic risk. 1
Patients with end-stage renal disease on hemodialysis can receive alteplase. 1
Patients with seizure at stroke onset should receive alteplase if residual deficits are stroke-related, not postictal. 1
3-4.5 Hour Window
IV Alteplase - Class I with Restrictions
- Administer IV alteplase using the same dosing protocol for patients ≤80 years old who meet ALL of the following criteria: 1
- No history of BOTH diabetes mellitus AND prior stroke
- NIHSS score ≤25
- Not taking oral anticoagulants
- No imaging evidence of ischemic injury >1/3 MCA territory
Extended Window Considerations (Class IIa/IIb)
Patients >80 years old may receive alteplase in the 3-4.5 hour window as it appears equally safe and effective. 1
Mild stroke symptoms (low NIHSS) may be treated, though risk-benefit must be carefully weighed. 1
Very severe strokes (NIHSS >25) have uncertain benefit in this window. 1
4.5-24 Hour Window (Wake-Up Strokes)
Advanced Imaging Selection
For patients last known well 4.5-24 hours ago, use MRI DWI-FLAIR mismatch to select candidates for IV alteplase when mechanical thrombectomy is not planned. 3
This represents high-quality evidence for extending thrombolysis beyond the traditional window in imaging-selected patients. 3, 4
Mechanical Thrombectomy
0-6 Hour Window - Class I Recommendations
Perform endovascular thrombectomy with stent retrievers for patients meeting ALL criteria: 5, 6
- Prestroke mRS 0-1
- Causative ICA or proximal MCA (M1) occlusion
- Age ≥18 years
- NIHSS ≥6
- ASPECTS ≥6
- Groin puncture achievable within 6 hours of onset
Administer IV alteplase first if eligible—do not delay thrombolysis for thrombectomy. 5, 6
6-24 Hour Window - Class I with Imaging Selection
Perform thrombectomy in the 6-24 hour window for patients with large vessel occlusion who meet eligibility criteria from major randomized trials (DAWN/DEFUSE-3 type selection with perfusion imaging showing salvageable tissue). 6, 7
Achieve TICI 2b/3 reperfusion as rapidly as possible; time remains critical even in extended windows. 5
Other Vessel Territories (Class IIb)
- Thrombectomy may be reasonable for M2/M3 MCA, anterior cerebral artery, vertebral artery, basilar artery, or posterior cerebral artery occlusions within 6 hours, though evidence is less robust. 5
Critical Management Points
Contraindications to Alteplase (Class III: Harm)
Do NOT give alteplase to patients on direct thrombin inhibitors or factor Xa inhibitors unless appropriate laboratory tests are normal or >48 hours since last dose with normal renal function. 1
Do NOT give alteplase with concurrent glycoprotein IIb/IIIa inhibitors. 1
Do NOT give alteplase for suspected infective endocarditis, aortic dissection, or intra-axial intracranial neoplasm. 1
Post-Treatment Antithrombotic Therapy
Avoid antithrombotic therapy for 24 hours after alteplase (with or without thrombectomy) unless compelling indication exists where withholding poses substantial risk. 1
This recommendation balances hemorrhagic risk against thrombotic complications. 1
Common Pitfalls
Do not delay alteplase administration for advanced imaging if patient is within 3-4.5 hours and meets clinical criteria—non-contrast CT is sufficient. 1
Do not withhold treatment from patients with preexisting disability (mRS ≥2) or dementia if they may achieve meaningful functional improvement. 1
Do not skip alteplase in thrombectomy candidates—combined therapy improves outcomes. 5, 7
Avoid excessive blood pressure lowering that causes hypoperfusion; target modest 15% reduction if treating hypertension acutely without reperfusion therapy. 2