Latest Ischemic Stroke Management Guidelines

Intravenous Thrombolysis: The Single Most Critical Intervention

Administer intravenous alteplase 0.9 mg/kg (maximum 90 mg) to all eligible patients presenting within 3–4.5 hours of symptom onset; this remains the only FDA-approved thrombolytic and the single most effective emergency intervention for acute ischemic stroke. 1, 2

Alteplase Administration Protocol

Give 10% of the total dose as an intravenous bolus over 1 minute, then infuse the remaining 90% over 60 minutes 3, 1
Target door-to-needle time ≤30 minutes (median) and ≤60 minutes (90th percentile); every 15-minute delay increases in-hospital mortality by 5% 1
When administered according to protocol criteria, approximately 37% of patients achieve complete functional independence 1

Blood Pressure Requirements for Thrombolysis

Before initiating alteplase, blood pressure must be reduced to <185/110 mmHg; patients who cannot achieve this target are absolutely ineligible for thrombolytic therapy. 3, 1, 4

Use intravenous labetalol 10–20 mg (may repeat once) or nicardipine infusion starting at 5 mg/hour (titrate by 2.5 mg/hour every 5–15 minutes, maximum 15 mg/hour) to lower pressure 4
During and for 24 hours after alteplase infusion, maintain blood pressure ≤180/105 mmHg 3, 1
Monitor blood pressure every 15 minutes for the first 2 hours, every 30 minutes for the next 6 hours, then hourly up to 24 hours 4

Absolute Contraindications to Alteplase

Intracranial hemorrhage at any time in the past 4
Recent (≤3 months) ischemic stroke or head trauma 4
Clinical features suggesting subarachnoid hemorrhage 4
Arterial puncture at a non-compressible site within 7 days 4
Platelet count <100,000/μL, INR >1.7, PT >15 seconds, or elevated aPTT if on heparin 4
Active internal bleeding 4

Tenecteplase: Emerging Alternative

While alteplase remains the FDA-approved standard, tenecteplase (0.25 mg/kg, maximum 25 mg) is emerging as a potentially superior alternative with easier bolus administration, lower cost, and comparable or better outcomes in recent trials. 5, 6, 7 However, alteplase should continue to be used until tenecteplase receives FDA approval and formal guideline endorsement.

Mechanical Thrombectomy: Endovascular Reperfusion

Perform mechanical thrombectomy with stent-retriever devices (Solitaire, Trevo) in patients with large-vessel occlusion who meet all eligibility criteria; this intervention is supported by the highest level of evidence from multiple randomized trials. 1

Thrombectomy Eligibility Criteria

Pre-stroke modified Rankin Scale 0–1 (functionally independent) 1
Age ≥18 years 1
NIHSS score ≥6 1
ASPECTS score ≥6 on non-contrast CT 1
Large-vessel occlusion (internal carotid artery or proximal M1 segment) confirmed on CT angiography 1
Groin puncture achievable within 6 hours of symptom onset 1
Selected patients meeting specific imaging criteria may be treated up to 12 hours after onset 1

Critical Workflow Principle

Never delay intravenous alteplase to perform endovascular thrombectomy; administer IV thrombolysis first if the patient is eligible, then proceed immediately to angiography. 1 The availability of intra-arterial therapy should not preclude IV alteplase administration. 3

Imaging Protocol

Initial Non-Contrast CT

Obtain non-contrast head CT within 25 minutes of emergency department arrival 1, 8, 4
Interpret the scan within 45 minutes (door-to-interpretation time) 1, 8
Early ischemic changes involving >1/3 of a cerebral hemisphere do NOT exclude alteplase use within 3 hours 4

CT Angiography

Perform CT angiography in all patients presenting within the thrombolysis or thrombectomy window to identify large-vessel occlusion. 1

Advanced Imaging Caution

Do not delay intravenous alteplase to obtain CT perfusion or multimodal MRI; rapid treatment is paramount and advanced imaging offers no outcome benefit when it causes delay. 1, 4

Blood Pressure Management in Non-Thrombolysis Candidates

Practice permissive hypertension in acute ischemic stroke unless systolic pressure exceeds 220 mmHg or diastolic exceeds 120 mmHg; aggressive lowering jeopardizes penumbral perfusion and worsens outcomes. 3, 1

If systolic pressure is <220 mmHg and diastolic <120 mmHg, initiating antihypertensive therapy within the first 48–72 hours does not reduce death or dependency (Class III, Level A evidence) 3
When pressure is ≥220/120 mmHg, a modest reduction of approximately 15% during the first 24 hours may be considered, though benefit is uncertain (Class IIb, Level C) 3, 1

Antiplatelet Therapy

Start aspirin 325 mg orally 24–48 hours after stroke onset to reduce early recurrent stroke; this timing is mandatory and supported by Class I, Level A evidence. 1

Critical Timing Restrictions

Never administer aspirin within 24 hours of alteplase administration; doing so significantly increases hemorrhage risk. 1
Obtain a repeat non-contrast head CT before starting aspirin to exclude hemorrhagic transformation 1
Aspirin is not a substitute for alteplase and should never delay thrombolytic therapy 1

Agents to Avoid in the Acute Phase

Clopidogrel alone or combined with aspirin is not recommended for acute ischemic stroke (Class III, Level C) 1
Intravenous glycoprotein IIb/IIIa inhibitors are not recommended outside clinical trials (Class III, Level B) 1

Anticoagulation: Strong Recommendation Against Acute Use

Do not use full-dose unfractionated heparin or low-molecular-weight heparin for acute ischemic stroke treatment; randomized trials demonstrate no functional benefit and significantly increased hemorrhage risk (Class III, Level A). 1

Emergency anticoagulation does not lower the risk of early recurrent stroke, even in cardioembolic sources 1
Anticoagulation does not prevent early neurological worsening 1

Intra-Arterial Thrombolysis

Consider intra-arterial thrombolysis for patients with major middle-cerebral-artery occlusion presenting <6 hours after onset who are ineligible for IV alteplase, but only at experienced stroke centers with immediate angiography capability (Class I, Level C). 3, 1

This approach is reasonable for patients with contraindications to IV thrombolysis, such as recent surgery (Class IIa, Level C) 3, 1
Delivery requires qualified interventionalists and comprehensive stroke-center resources 3, 1

Hospital Admission and Stroke Unit Care

Admit all stroke patients to a dedicated stroke unit with monitored beds; stroke unit care reduces mortality and morbidity to a degree comparable to the effects of alteplase itself. 3, 1

Monitoring and Supportive Care

Maintain oxygen saturation ≥92% using pulse oximetry; provide supplemental oxygen only when saturation falls below 94% 1
Check core temperature every 4 hours for the first 48 hours and treat fever aggressively (target ≤37.5°C); hyperthermia worsens neurological damage 3, 1
Assess swallowing function before any oral intake to prevent aspiration 1, 8

Early Mobilization

Initiate early mobilization (sitting, standing, brief ambulation) within 24 hours of admission if no contraindications exist 1, 8

Venous Thromboembolism Prophylaxis

Apply intermittent pneumatic compression devices within 24 hours of admission for immobile patients 1, 8
When pharmacologic prophylaxis is indicated, use prophylactic-dose low-molecular-weight heparin rather than unfractionated heparin 1

Secondary Prevention (Initiated During Hospitalization)

Long-Term Antiplatelet Therapy

For ongoing secondary prevention, prescribe clopidogrel 75 mg daily or aspirin 75–100 mg plus extended-release dipyridamole 25 mg/200 mg twice daily; these regimens are superior to aspirin alone 1
Do not combine clopidogrel with aspirin for chronic secondary prevention 1

Atrial Fibrillation

In patients with ischemic stroke and atrial fibrillation, prescribe oral anticoagulation (warfarin or a direct oral anticoagulant) rather than antiplatelet therapy alone. 1

Prehospital and System-Level Care

Emergency medical services should transport suspected stroke patients directly to the nearest Primary or Comprehensive Stroke Center, bypassing facilities lacking stroke-treatment capabilities 1
Paramedics must provide prehospital notification with detailed patient information to ensure the stroke team is ready on arrival 1

Common Pitfalls to Avoid

Do not withhold alteplase solely because the NIHSS score is ≥25; patients with severe strokes may still benefit when treated within 4.5 hours 4
Do not delay IV alteplase to obtain advanced imaging (CT perfusion, MRI) in patients presenting within the 3–4.5-hour window 1, 4
Protocol violations during alteplase administration significantly increase the risk of symptomatic intracranial hemorrhage and mortality; strict adherence is mandatory 3
Do not aggressively lower blood pressure in acute stroke unless giving thrombolytics or BP >220/120 mmHg; permissive hypertension maintains penumbral perfusion 3, 1

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