What is the initial drug of choice for treating ischemic (ischaemic) stroke?

Initial Drug Treatment for Acute Ischaemic Stroke

For patients presenting within 3 hours of symptom onset, intravenous recombinant tissue plasminogen activator (IV r-tPA/alteplase) at 0.9 mg/kg (maximum 90 mg) is the definitive first-line treatment, with 10% given as a bolus over 1 minute and the remainder infused over 60 minutes. 1

Time-Based Treatment Algorithm

Within 3 Hours of Symptom Onset

• IV r-tPA is strongly recommended (Grade 1A evidence) as it significantly improves functional outcomes, with a number needed to treat of approximately 8 for achieving minimal or no disability 1
• This represents the strongest evidence base with FDA approval for this time window 1
• Treatment produces a 12% absolute increase in patients achieving minimal or no disability (modified Rankin Scale 0-1: 39% vs 26% placebo) 1

Between 3 to 4.5 Hours of Symptom Onset

• IV r-tPA should be considered using ECASS III criteria (Grade 2C evidence) 1
• This time window is not FDA-approved but supported by guideline recommendations 1
• The evidence is less robust than the 0-3 hour window, but still demonstrates benefit 1

Beyond 4.5 Hours of Symptom Onset

• IV r-tPA is NOT recommended (Grade 1B evidence against use) 1
• Studies beyond 5 hours showed no benefit and increased hemorrhagic complications 2

Critical Dosing Specifications

The standard dose is 0.9 mg/kg with a maximum of 90 mg total: 1

• 10% administered as IV bolus over 1 minute
• Remaining 90% infused over 60 minutes
• This dosing regimen is based on the landmark NINDS trial 1

Aspirin as Alternative/Adjunctive Therapy

For patients who cannot receive r-tPA or after the thrombolytic window has closed, aspirin 160-325 mg should be initiated within 48 hours (Grade 1A evidence) 1, 3

Critical Aspirin Timing Restrictions:

• Aspirin must NOT be given within 24 hours of r-tPA administration due to increased bleeding risk 1, 3
• Aspirin is NOT a substitute for r-tPA in eligible patients 3
• Early aspirin reduces early recurrent stroke but does not limit neurological consequences of the initial stroke 3

Important Safety Considerations

Blood Pressure Management Before r-tPA:

• Systolic BP must be ≤185 mm Hg and diastolic ≤105 mm Hg before treatment 1
• Blood pressure requiring continuous sodium nitroprusside infusion may be too unstable for r-tPA administration 1

Hemorrhagic Complications:

• Symptomatic intracerebral hemorrhage occurs in approximately 3.3-7% of treated patients 4, 2
• Risk increases significantly with protocol violations, particularly treatment beyond 3 hours 4
• Fatal ICH occurs in approximately 3% of cases when protocols are violated 2

Post-Treatment Monitoring Protocol:

• Neurological assessments every 15 minutes during infusion, then every 30 minutes for 6 hours, then hourly until 24 hours 1
• Blood pressure monitoring every 15 minutes for 2 hours, then every 30 minutes for 6 hours, then hourly 1
• Follow-up CT scan at 24 hours before starting any antiplatelet or anticoagulant therapy 1

Common Pitfalls to Avoid

Protocol violations occurred in 32.6% of patients in real-world practice and significantly worsen outcomes: 4

• Treating beyond 3 hours without meeting extended criteria (13.4% violation rate)
• Administering anticoagulants within 24 hours of r-tPA (9.3% violation rate)
• Treating despite elevated blood pressure >185/105 mm Hg (6.7% violation rate)

Do not use alternative thrombolytics: Streptokinase, tenecteplase, reteplase, desmoteplase, and urokinase are NOT recommended outside clinical trials (Grade III) 1

Anticoagulation Is NOT Recommended Acutely

Urgent anticoagulation with heparin, low-molecular-weight heparin, or heparinoids does NOT improve outcomes and increases bleeding risk (Grade 1A evidence against) 1

• These agents increase symptomatic hemorrhagic transformation, especially in severe strokes 1
• Aspirin is preferred over therapeutic anticoagulation in the acute setting 1

Special Circumstances

Intraarterial r-tPA:

• May be considered for proximal cerebral artery occlusions within 6 hours in patients ineligible for IV r-tPA (Grade 2C) 1
• Requires immediate access to cerebral angiography and experienced stroke center 1

Mechanical Thrombectomy:

• The 2012 guidelines suggested against routine use (Grade 2C), though this recommendation predates modern thrombectomy trials 1