What is the treatment for ischemic stroke?

Treatment of Acute Ischemic Stroke

For acute ischemic stroke patients presenting within 3 hours of symptom onset, administer IV recombinant tissue plasminogen activator (r-tPA) at 0.9 mg/kg (maximum 90 mg) as first-line therapy, followed by aspirin 160-325 mg within 48 hours. 1, 2

Acute Thrombolytic Therapy: Time-Based Algorithm

Within 0-3 Hours of Symptom Onset

• Strongly recommend IV r-tPA (Grade 1A evidence) 1, 2
• Dosing: 0.9 mg/kg (maximum 90 mg) administered over 1 hour 2
• This represents the highest quality evidence with 154 more favorable events per 1,000 patients treated 2
• Patients treated within this window are at least 30% more likely to have minimal or no disability at 3 months 3

Within 3-4.5 Hours of Symptom Onset

• Suggest IV r-tPA (Grade 2C evidence - weaker recommendation) 1, 2
• Same dosing protocol: 0.9 mg/kg (maximum 90 mg) 2
• Smaller benefit: 69 more favorable events per 1,000 patients 2
• The evidence is less robust in this window, but treatment may still provide benefit 1

Beyond 4.5 Hours of Symptom Onset

• Recommend against IV r-tPA (Grade 1B evidence) 1
• The ATLANTIS trial found no significant benefit and increased symptomatic intracerebral hemorrhage (ICH) risk (7.0% vs 1.1%, p<0.001) when treating between 3-5 hours 4
• Fatal ICH increased significantly (3.0% vs 0.3%, p<0.001) 4

Alternative Interventions for Specific Scenarios

Proximal Cerebral Artery Occlusions (Ineligible for IV r-tPA)

• Consider intraarterial r-tPA within 6 hours of symptom onset (Grade 2C) 1, 2
• This applies only to patients who do not meet IV r-tPA eligibility criteria 1

Mechanical Thrombectomy

• Generally not recommended (Grade 2C) 1, 2
• The 2012 guidelines suggest against routine use, though carefully selected patients who highly value uncertain benefits over risks may choose this intervention 1
• Note: These guidelines predate newer stent retriever devices, which were rarely used in the trials informing these recommendations 5

Adjunctive Acute Therapies

Antiplatelet Therapy

• Administer aspirin 160-325 mg within 48 hours of stroke onset (Grade 1A) 1, 2
• Aspirin is strongly preferred over therapeutic parenteral anticoagulation in acute stroke (Grade 1A) 1
• Do not delay aspirin for difficult IV access 2, 3

Venous Thromboembolism Prophylaxis

• For patients with restricted mobility, use prophylactic-dose subcutaneous low-molecular-weight heparin (LMWH) as preferred method (Grade 2B) 1, 2
• LMWH is preferred over unfractionated heparin (Grade 2B) 1
• Alternative: intermittent pneumatic compression devices (Grade 2B) 1
• Avoid elastic compression stockings (Grade 2B) 1

Long-Term Secondary Prevention

For Noncardioembolic Stroke

• Recommend long-term antiplatelet therapy (Grade 1A) with one of the following: 1
  • Clopidogrel 75 mg once daily (preferred)
  • Aspirin/extended-release dipyridamole 25 mg/200 mg twice daily (preferred)
  • Aspirin 75-100 mg once daily
  • Cilostazol 100 mg twice daily
• Clopidogrel or aspirin/extended-release dipyridamole are preferred over aspirin alone (Grade 2B) 1
• The CAPRIE trial showed clopidogrel reduced vascular events compared to aspirin (9.8% vs 10.6%, relative risk reduction 8.7%, p=0.045), though benefit was less apparent specifically in stroke patients 6
• Avoid long-term combination of clopidogrel plus aspirin (Grade 1B) 1

For Cardioembolic Stroke (Atrial Fibrillation)

• Recommend oral anticoagulation over antiplatelet therapy (Grade 1A) 1
• Dabigatran 150 mg twice daily is suggested over warfarin (Grade 2B) 1
• Initiate anticoagulation within 1-2 weeks after stroke onset 1
• Bridge with aspirin until therapeutic anticoagulation is achieved 1

Critical Procedural Considerations

IV Access

• Establish IV access in the non-paretic arm to preserve the affected limb for rehabilitation 2, 3
• If non-paretic arm access is impossible, use the most distal site possible in the paretic arm and monitor frequently 3
• Consider alternative sites (external jugular vein, central line) if peripheral access fails 3
• Do not delay thrombolytic treatment for difficult IV access - consider alternative methods 2, 3

Common Pitfalls and Caveats

Hemorrhage Risk Assessment

• Carefully exclude patients with evidence of intracranial hemorrhage on imaging before administering r-tPA 7
• Symptomatic ICH risk increases significantly with r-tPA treatment (7.0% vs 1.1% in the 3-5 hour window) 4
• A history of cerebral hemorrhage is not an absolute contraindication; one study found no significant increase in SICH (8.3% vs 4.6%, p=0.610) with careful patient selection 8

Drug Interactions

• Avoid omeprazole or esomeprazole in patients taking clopidogrel, as these significantly reduce antiplatelet activity 6
• Dexlansoprazole, lansoprazole, and pantoprazole have less pronounced effects 6

Time Calculation

• For wake-up stroke: use midpoint between time last known well (or sleep onset) and wake-up time 9
• For unknown onset time: use midpoint between time last known well and symptom recognition 9

Genetic Considerations

• CYP2C19 poor metabolizers (2% of White, 4% of Black, 14% of Chinese patients) have reduced clopidogrel efficacy 6
• Consider genetic testing if clopidogrel is chosen for long-term therapy 6