What is the best treatment for an ischemic stroke?

Best Treatment for Ischemic Stroke

Intravenous alteplase (0.9 mg/kg, maximum 90 mg) administered within 4.5 hours of symptom onset is the first-line treatment for acute ischemic stroke, with the strongest evidence supporting administration within 3 hours. 1

Acute Treatment Algorithm

1. Intravenous Thrombolysis

• Time window considerations:

  • Within 3 hours: Strong recommendation for IV alteplase (Grade 1A) 2
  • 3-4.5 hours: Conditional recommendation for IV alteplase (Grade 2C) 2
  • Beyond 4.5 hours: Not recommended (Grade 1B) 2

• Dosing protocol:

  • 0.9 mg/kg (maximum 90 mg)
  • 10% as IV bolus over 1 minute
  • Remaining 90% as IV infusion over 60 minutes 2, 1

• Target door-to-needle time:

  • Less than 60 minutes in 90% of treated patients
  • Median time of 30 minutes 2, 1

2. Endovascular Thrombectomy (EVT)

• Indicated for patients with proximal large vessel occlusions
• Can be performed within 6 hours of symptom onset
• Should be offered within a coordinated system of care 2
• Appropriate for both patients who have received IV alteplase and those who are ineligible 2

3. Antithrombotic Therapy

• Early aspirin therapy (160-325 mg) should be initiated within 24-48 hours after stroke onset 2, 1
• For patients treated with IV alteplase, delay aspirin for 24 hours 1

Post-Treatment Management

1. Monitoring

• Neurological assessments every 15 minutes during infusion and for 2 hours
• Then every 30 minutes for 6 hours
• Then hourly until 24 hours after treatment 1

2. Blood Pressure Management

• Target BP ≤185/110 mmHg before initiating IV thrombolysis
• Maintain BP <180/105 mmHg during and for 24 hours after treatment 1
• Options for BP control: labetalol, nicardipine, clevidipine 1

3. Complication Management

• Angioedema: Staged response using antihistamines, glucocorticoids, and standard airway management 2
• Bleeding: Individualized approach; insufficient evidence for routine use of blood products 2

4. DVT Prophylaxis

• Prophylactic-dose subcutaneous heparin (preferably LMWH) for immobile patients 1
• Intermittent pneumatic compression devices as an alternative to heparin (Grade 2B) 2, 1
• Early mobilization and adequate hydration 1

Evidence Quality and Considerations

The recommendation for IV alteplase is supported by high-quality evidence, particularly for administration within 3 hours of symptom onset. The ECASS III trial demonstrated that alteplase administered between 3-4.5 hours after stroke onset significantly improved clinical outcomes compared to placebo, though with a slightly increased risk of symptomatic intracranial hemorrhage (2.4% vs. 0.2%) 3.

Some studies have investigated low-dose alteplase (0.6 mg/kg), which is common in East Asian countries. While the ENCHANTED trial did not demonstrate noninferiority of low-dose alteplase compared to standard-dose for death and disability at 90 days, it did show fewer symptomatic intracerebral hemorrhages with the lower dose 4. However, current guidelines still recommend the standard dose of 0.9 mg/kg 2, 1.

Cautions and Contraindications

• Contraindications for IV alteplase:

  • Symptom onset >4.5 hours
  • Unknown time of symptom onset
  • Another stroke or serious head injury within preceding 3 months
  • Major surgery within prior 14 days
  • History of intracranial hemorrhage
  • Gastrointestinal or genitourinary hemorrhage within previous 21 days 1

• Important note: The dosing of alteplase for stroke is not the same as the dosing protocol for myocardial infarction 2

• For patients on DOACs: Alteplase should not routinely be administered; EVT may be considered in these cases 2