What is the recommended loading dose of aspirin (acetylsalicylic acid) in the management of ischemic stroke?

Aspirin Loading Dose in Acute Ischemic Stroke

For acute ischemic stroke, administer aspirin 160-325 mg within 24-48 hours of symptom onset—this is the recommended loading dose that reduces early recurrent stroke and mortality. 1, 2

Dosing Specifications

• Initial dose range: 160-325 mg administered orally, rectally, or via nasogastric tube if the patient cannot safely swallow 1
• The 2018 AHA/ASA guidelines removed the specific "325 mg" recommendation because pivotal trials (IST and CAST) used doses between 160-300 mg with equivalent efficacy 1
• Timing: Within 24-48 hours of stroke onset is the evidence-based window 1, 2

Critical Contraindications and Timing Restrictions

Do NOT give aspirin within 24 hours of IV alteplase (tPA) administration due to increased bleeding risk—wait the full 24 hours after thrombolytic therapy before starting aspirin 1, 2

Aspirin is NOT a substitute for IV thrombolysis or mechanical thrombectomy in eligible patients—these reperfusion therapies take absolute priority 1, 2

Additional contraindications include:

• Active gastrointestinal bleeding 2
• Aspirin allergy 2
• Severe thrombocytopenia or coagulopathy

Evidence Quality and Mechanism

The Class I, Level of Evidence A recommendation is based on two landmark trials (IST with 20,000 patients and CAST) showing:

• 14% reduction in mortality during the treatment period 3
• Significant reduction in early recurrent ischemic stroke (1.6% vs 2.1%, p=0.01) 3
• The primary benefit is prevention of early recurrent stroke, not limitation of the initial stroke's neurological damage 2

Alternative Antiplatelet Agents in Acute Stroke

Clopidogrel monotherapy is NOT recommended for routine acute ischemic stroke treatment (Class IIb, Level C evidence) 2

Dual antiplatelet therapy (aspirin + clopidogrel) has a specific niche indication:

• For minor stroke only (not moderate-to-severe stroke), dual therapy started within 24 hours can be beneficial 1
• Loading: clopidogrel 600 mg + aspirin 50-325 mg on day 1 4
• Continue for 21 days for secondary prevention up to 90 days 1
• Important caveat: The POINT trial showed dual therapy reduces major ischemic events (5.0% vs 6.5%, HR 0.75) but increases major hemorrhage (0.9% vs 0.4%, HR 2.32) 4

Ticagrelor is NOT recommended over aspirin in acute minor stroke (Class III: No Benefit) 1

IV glycoprotein IIb/IIIa inhibitors (abciximab, tirofiban, eptifibatide) should not be used outside clinical trials—abciximab is potentially harmful (Class III: Harm) 1

Common Pitfalls to Avoid

1. Giving aspirin too early after tPA: Always wait 24 hours post-thrombolysis unless there's a compelling indication where withholding aspirin poses substantial risk 1, 2

2. Using aspirin instead of tPA: Never substitute aspirin for reperfusion therapy in eligible patients—aspirin is adjunctive, not primary acute treatment 1, 2

3. Overdosing beyond 325 mg: Higher doses increase gastrointestinal bleeding without additional efficacy 5

4. Using dual antiplatelet therapy in moderate-to-severe stroke: The dual therapy indication is specifically for minor stroke/high-risk TIA only 1, 4