What is the recommended acute management for an adult (≥18 years) presenting with ischemic stroke within 4.5 hours of symptom onset, including criteria for intravenous alteplase, indications for mechanical thrombectomy, blood pressure and glucose targets, and subsequent antiplatelet, statin, and supportive care?

Management of Acute Ischemic Stroke

Immediate Assessment and IV Alteplase Administration (0-4.5 Hours)

For adults presenting within 4.5 hours of symptom onset, administer IV alteplase (0.9 mg/kg, maximum 90 mg) immediately after excluding hemorrhage on non-contrast CT, with 10% given as bolus over 1 minute and 90% infused over 60 minutes. 1, 2, 3

Critical Pre-Treatment Requirements

• Blood pressure must be lowered to <185/110 mmHg before initiating alteplase and maintained <180/105 mmHg for 24 hours post-treatment 1, 2, 3
• Only blood glucose assessment must precede alteplase administration—do not delay for other tests 3
• Non-contrast CT must exclude intracranial hemorrhage and extensive early ischemic changes (>1/3 MCA territory) 1, 2, 3
• Blood glucose must be >50 mg/dL 1

Time Window-Specific Criteria

0-3 Hour Window:

• All patients ≥18 years meeting basic eligibility criteria should receive alteplase, including those >80 years old 1, 3
• Severe stroke (high NIHSS) is not a contraindication within 3 hours 1
• Prior antiplatelet monotherapy or dual antiplatelet therapy (aspirin + clopidogrel) is not a contraindication 1
• End-stage renal disease on hemodialysis with normal aPTT is not a contraindication 1

3-4.5 Hour Window:

• Exclude patients if they meet ANY of these criteria: age >80 years, oral anticoagulant use (regardless of INR), NIHSS >25, or history of both diabetes AND prior stroke 1, 3
• All other standard eligibility criteria apply 1

Absolute Contraindications

• Unclear or unwitnessed symptom onset with last known well >3 or 4.5 hours 1
• Intracranial hemorrhage on CT 1
• Extensive regions of clear hypoattenuation (obvious hypodensity) on CT 1
• Prior ischemic stroke within 3 months 1
• Severe head trauma within 3 months 1

Common Pitfall: Do not withhold alteplase in patients with prior cerebral hemorrhage history—this is not an absolute contraindication, though it increases symptomatic ICH risk from 4.3% to 8.3% without affecting 90-day outcomes 4

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Mechanical Thrombectomy for Large Vessel Occlusion

For patients with suspected large vessel occlusion (LVO), obtain CT angiography immediately and proceed with mechanical thrombectomy evaluation WITHOUT waiting to assess IV alteplase response. 3

Thrombectomy Algorithm

• Administer IV alteplase first if within 4.5 hours and eligible—do not delay alteplase to evaluate for thrombectomy 3
• Obtain non-invasive angiography (CTA) for all patients with clinically suspected LVO 3
• If anterior circulation LVO confirmed within 6-24 hours, obtain advanced imaging (CTP or DW-MRI) to determine thrombectomy eligibility 3
• Proceed directly to catheter angiography without evaluating alteplase response 3

Evidence for Combined Therapy

• Modern stent retrievers achieve 72-88% recanalization rates compared to near-zero with IV therapy alone for high clot burden 3
• Combined IV alteplase plus thrombectomy provides a 50% increase in good functional outcomes versus medical therapy alone 3
• Symptomatic ICH rates are similar between thrombectomy (4.4%) and control (4.3%) groups 3
• Number needed to treat is approximately 3-4 patients for one additional good outcome 3

Critical Point: The 2015 landmark trials (MR CLEAN, ESCAPE, SWIFT PRIME, EXTEND-IA, REVASCAT) established thrombectomy as standard of care for LVO 3

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Extended Window Thrombolysis (4.5-9 Hours or Wake-Up Stroke)

For patients presenting 4.5-9 hours after symptom onset, consider IV alteplase ONLY if CT/MRI shows core-perfusion mismatch AND mechanical thrombectomy is not indicated or planned. 5, 6

Selection Criteria for Extended Window

• CT or MRI perfusion demonstrating core-perfusion mismatch is required for 4.5-9 hour window 5, 6
• For wake-up strokes or unclear onset time, MRI with DWI-FLAIR mismatch is required 5, 6
• CT angiography must exclude large vessel occlusion (if LVO present, thrombectomy is preferred over late alteplase) 5
• All standard alteplase contraindications still apply 5

Important Caveat: The 2023 World Stroke Organization guidelines supersede older AHA/ASA recommendations that contraindicated alteplase beyond 4.5 hours for wake-up strokes 5

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Blood Pressure Management

Pre-Alteplase Blood Pressure Targets

• Lower BP to <185/110 mmHg before initiating alteplase using antihypertensive agents 1, 2
• Assess BP stability before starting treatment 1

Post-Alteplase Blood Pressure Monitoring

• Maintain BP <180/105 mmHg for at least 24 hours after alteplase 2, 3
• Monitor every 15 minutes for first 2 hours, every 30 minutes for next 6 hours, then hourly until 24 hours 3

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Glucose Management

• Blood glucose must be >50 mg/dL before alteplase administration 1
• Hyperglycemia >11.1 mmol/L (200 mg/dL) significantly increases hemorrhagic complication risk—baseline glucose >11.1 mmol/L is associated with 36% risk of symptomatic ICH 3
• Correct glucose if <60 mg/dL or >400 mg/dL before treatment 5

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Post-Alteplase Monitoring and Management

Neurological Monitoring

• Assess neurological status every 15 minutes during infusion, every 30 minutes for 6 hours, then hourly until 24 hours 3
• If severe headache, acute hypertension, nausea, or vomiting occur, stop infusion immediately and obtain emergent CT 3

Antithrombotic Therapy

• Avoid all antithrombotic therapy (antiplatelet and anticoagulant) for 24 hours after alteplase 2, 3
• Obtain follow-up CT at 24 hours before starting any antiplatelet or anticoagulant therapy 3

Procedural Precautions

• Delay placement of nasogastric tubes, indwelling bladder catheters, and intra-arterial pressure catheters until after the 24-hour monitoring period 3
• Monitor for angioedema as potential adverse effect causing partial airway obstruction 3

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Subsequent Antiplatelet and Statin Therapy

• After 24-hour post-alteplase period and follow-up CT excluding hemorrhage, initiate antiplatelet therapy 3
• Standard stroke secondary prevention with statin therapy should be initiated once acute phase management is complete 3

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Institutional Requirements for Safe Alteplase Use

Alteplase effectiveness is less well established in hospitals lacking organized stroke systems. Required components include: 3

• 24/7 rapid CT availability
• Dedicated stroke team
• Continuous neurological monitoring capability
• Blood pressure management protocols
• Neurosurgical consultation availability

Time-Dependent Outcomes: Every 15-minute delay in treatment reduces likelihood of favorable outcome—the "time-is-brain" principle mandates maximum urgency 3, 7. Adjusted odds of favorable 3-month outcome are 2.55 for 0-90 minutes, 1.64 for 91-180 minutes, 1.34 for 181-270 minutes, and 1.22 for 271-360 minutes 7.