In a 50-year-old patient who arrived 7 hours after stroke onset with a distal A2 occlusion, a small core and large mismatch on CT perfusion but no diffusion‑weighted imaging–FLAIR mismatch on MRI, should intravenous alteplase be administered?

IV Alteplase Administration in the 4.5-9 Hour Window

For this patient presenting at 7 hours with a distal A2 occlusion, small core, and large perfusion mismatch on CT perfusion, you should administer IV alteplase at 0.9 mg/kg (maximum 90 mg) based on the 2025 HOPE trial demonstrating functional benefit in this extended window when salvageable tissue is present. 1

Evidence-Based Algorithm for Extended Window Treatment (4.5-24 Hours)

Step 1: Confirm Timing Eligibility

• Patient must present between 4.5 and 24 hours from symptom onset (or midpoint of last known well to symptom recognition if onset unknown) 1, 2
• For wake-up strokes, use the midpoint between last known well/sleep onset and wake-up time 3
• This patient at 7 hours falls within the eligible window 1

Step 2: Verify Advanced Imaging Criteria

CT or MRI perfusion imaging must demonstrate: 1, 4

• Ischemic core volume ≤70 mL
• Penumbra ≥10 mL
• Mismatch ratio ≥20%

Your patient meets these criteria with small core and large mismatch 1

Step 3: Confirm No Initial Plan for Thrombectomy

• The distal A2 occlusion is not a typical large vessel occlusion target for mechanical thrombectomy 1
• Extended window alteplase is specifically indicated when thrombectomy is not planned 4, 1
• This is a critical distinction: the HOPE trial excluded patients with planned endovascular therapy 1

Step 4: Apply Standard Alteplase Contraindications

• Blood pressure must be <185/110 mmHg before treatment 5, 6
• No intracranial hemorrhage on imaging 5
• Blood glucose >50 mg/dL (this is the only mandatory pre-treatment lab) 5, 7
• No recent surgery, active bleeding, or coagulopathy 5

Critical Evidence Supporting This Recommendation

The 2025 HOPE trial is the highest-quality and most recent evidence addressing this exact clinical scenario: 1

• 372 patients randomized between 4.5-24 hours with salvageable tissue on perfusion imaging
• Primary outcome (mRS 0-1 at 90 days): 40% with alteplase vs 26% with standard care (adjusted RR 1.52,95% CI 1.14-2.02, P=0.004)
• Symptomatic ICH increased from 0.51% to 3.8% (acceptable given functional benefit)
• No difference in mortality (11% in both groups)

This supersedes the negative 2019 ECASS-4 trial, which was underpowered (stopped early at 119 of 264 planned patients) and showed no benefit 8

The DWI-FLAIR Mismatch Issue

Your patient does NOT have DWI-FLAIR mismatch on MRI, but this is irrelevant because: 6, 1

• DWI-FLAIR mismatch is specifically for wake-up strokes or unknown onset time when perfusion imaging is unavailable 6
• Your patient has a known 7-hour onset time and has CT perfusion demonstrating salvageable tissue 1
• CT perfusion mismatch is the superior selection method and was used in the HOPE trial 1

Dosing and Administration

Administer alteplase 0.9 mg/kg (maximum 90 mg): 5, 7

• 10% as IV bolus over 1 minute
• Remaining 90% infused over 60 minutes
• No dose adjustment needed for vessel occlusion location or NIHSS score 7

Safety Monitoring

• Avoid antithrombotic agents for 24 hours post-treatment 7
• Monitor neurological status closely for hemorrhagic transformation 7
• Maintain blood pressure <180/105 mmHg for 24 hours after treatment 7

Common Pitfalls to Avoid

Do not withhold alteplase because: 1, 2

• The occlusion is "too distal" - the HOPE trial included all vessel locations
• The patient is beyond 4.5 hours - this is precisely the population that benefits with perfusion selection
• You're waiting for "natural improvement" - earlier treatment within the extended window is better

Do not confuse DWI-FLAIR mismatch (for wake-up strokes) with CT perfusion mismatch (for known onset times) - they serve different purposes in patient selection 6, 1