In patients admitted with acute ischemic stroke, how long should aspirin be administered at a dose of 160–325 mg daily?

Aspirin Duration After Acute Ischemic Stroke Admission

Aspirin 160–325 mg daily should be administered for the first 24–48 hours as a loading dose, then continued at 75–100 mg daily indefinitely for long-term secondary stroke prevention. 1

Initial Loading Phase (First 24–48 Hours)

• Administer aspirin 160–325 mg within 24–48 hours of stroke onset after intracranial hemorrhage has been excluded on neuroimaging. 1
• If the patient received IV alteplase, delay aspirin until 24 hours after thrombolysis to minimize hemorrhagic risk, though earlier administration may be considered if compelling cardiac or other vascular indications exist. 1
• The loading dose ensures rapid and complete inhibition of thromboxane A2-dependent platelet aggregation in the acute setting. 2

Transition to Maintenance Dosing (Day 2 Onward)

• Switch to aspirin 75–100 mg daily starting on day 2 and continue indefinitely for secondary stroke prevention. 2, 3
• This maintenance dose provides equivalent efficacy to higher doses while minimizing gastrointestinal bleeding risk. 2
• The 2018 AHA/ASA guideline removed the specific "initial dose is 325 mg" recommendation because clinical trials supporting aspirin use included doses of 160–300 mg. 1

Special Consideration: Minor Stroke or High-Risk TIA

For patients with minor stroke (NIHSS ≤3) or high-risk TIA (ABCD² ≥4) presenting within 24 hours:

• Initiate dual antiplatelet therapy instead of aspirin alone: loading dose of aspirin 160–325 mg plus clopidogrel 300–600 mg within 24 hours. 2
• Continue aspirin 75–100 mg daily plus clopidogrel 75 mg daily for exactly 21 days. 2
• After 21 days, transition to single antiplatelet therapy (aspirin 75–100 mg daily OR clopidogrel 75 mg daily) indefinitely. 2
• Do not extend dual therapy beyond 21–30 days, as bleeding risk outweighs benefit (hazard ratio 2.22–2.32 for major hemorrhage). 2

Alternative Routes for Patients Unable to Swallow

• Rectal aspirin 325 mg daily or aspirin 81 mg daily via enteral tube are reasonable alternatives for patients with dysphagia. 2
• Avoid enteric-coated aspirin for the loading dose, as it delays absorption when rapid platelet inhibition is needed. 3, 4

Evidence Supporting This Approach

• Two large trials (IST and CAST) involving over 40,000 patients demonstrated that aspirin 160–300 mg started within 48 hours reduced death or dependency by 13 events per 1,000 patients treated (number needed to treat: 79). 5, 6
• The benefit is time-dependent, with maximum efficacy when started within the first 24–48 hours. 2
• Early aspirin reduces recurrent ischemic stroke from 2.1% to 1.6% without major hemorrhagic complications. 7, 8

Critical Contraindications

• Do not use aspirin as a substitute for thrombolysis or mechanical thrombectomy in eligible patients, as this delays definitive treatment and worsens outcomes. 1
• Absolute contraindications include: active intracranial hemorrhage, active gastrointestinal bleeding, known aspirin allergy, and severe thrombocytopenia. 2

Common Pitfalls to Avoid

• Do not delay aspirin beyond 48 hours when eligibility criteria are met; the benefit is time-dependent. 2
• Do not continue high-dose aspirin (>100 mg daily) for maintenance therapy after the initial loading dose, as this increases bleeding risk without improving outcomes. 2
• Do not use glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), as they are potentially harmful in acute ischemic stroke. 1