Aspirin Dosing for Large Ischemic Stroke
For patients with large ischemic stroke, administer 160-300 mg aspirin within 24-48 hours after symptom onset (once intracranial hemorrhage is excluded on imaging), followed by 75-100 mg daily for long-term secondary prevention. 1, 2
Acute Phase Dosing (First 24-48 Hours)
Initial dose: 160-300 mg aspirin should be administered within 24-48 hours of stroke onset after brain imaging excludes hemorrhagic transformation. 1, 2 This recommendation is based on Class I, Level A evidence from two landmark trials (CAST and IST) that collectively enrolled over 40,000 patients and demonstrated significant reduction in early recurrent stroke and mortality. 1, 2
Critical Timing Considerations for Large Strokes
If the patient received IV alteplase (tPA), delay aspirin for 24 hours after thrombolytic administration to minimize hemorrhagic risk. 1, 2 This is particularly important in large MCA territory strokes given their higher propensity for hemorrhagic transformation. 2
Aspirin is NOT a substitute for acute reperfusion therapy (IV thrombolysis or mechanical thrombectomy) and should never delay these interventions. 1
For patients unable to swallow, use rectal aspirin 325 mg or nasogastric administration of 160-300 mg. 1
Chew the aspirin when possible for faster buccal absorption and more rapid antiplatelet effect. 2
Why This Specific Dose Range?
The 2018 AHA/ASA guidelines deliberately removed the previous "325 mg" specific recommendation because the pivotal trials used doses between 160-300 mg, all of which proved effective. 1 The 2012 CHEST guidelines recommend 160-325 mg, which overlaps substantially with this range. 1
Long-Term Secondary Prevention Dosing
Maintenance dose: 75-100 mg aspirin daily indefinitely for secondary stroke prevention. 1, 2 This lower maintenance dose provides equivalent efficacy to higher doses (300-325 mg) but with significantly reduced bleeding risk, particularly gastrointestinal complications. 2, 3
The 2023 World Stroke Organization synthesis recommends 81-325 mg daily for long-term therapy, though the lower end of this range (75-100 mg) is preferred based on safety data. 1
Special Considerations for Large MCA Strokes
Hemorrhagic Transformation Risk
Large MCA territory strokes carry substantially higher risk of hemorrhagic transformation compared to smaller strokes. 2 This makes the following critical:
- Always obtain brain imaging before any aspirin administration to exclude hemorrhage. 1, 2
- The 24-48 hour window allows assessment of stroke evolution and hemorrhagic risk before committing to antiplatelet therapy. 1, 2
- Serial neurological examinations and repeat imaging should guide the decision to initiate aspirin in patients with massive strokes showing signs of malignant edema. 1
What NOT to Do in Large Strokes
Do not use dual antiplatelet therapy (aspirin + clopidogrel) in large territorial strokes. 1, 2 DAPT is reserved exclusively for minor strokes (NIHSS ≤3-5) or high-risk TIA, not large MCA strokes where bleeding risk outweighs benefit. 1
Do not use clopidogrel monotherapy acutely as an alternative to aspirin in large strokes—the evidence base supports aspirin specifically. 1
Avoid glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) as they are potentially harmful in acute ischemic stroke. 1
Alternative Antiplatelet Agents
If the patient has a documented aspirin allergy or contraindication, alternative antiplatelet agents may be reasonable, though evidence is limited in the acute setting. 1 For long-term secondary prevention after the acute phase, clopidogrel 75 mg daily or aspirin/extended-release dipyridamole 25/200 mg twice daily are acceptable alternatives. 1
Evidence Strength Summary
This recommendation carries Class I, Level A evidence—the highest grade possible. 1 The International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST) demonstrated that aspirin 160-300 mg initiated within 48 hours resulted in 14% reduction in early mortality and significant reduction in recurrent ischemic stroke. 4 The number needed to treat is approximately 100 patients to prevent one death or recurrent stroke in the first few weeks. 1
Common Pitfalls to Avoid
- Do not delay aspirin beyond 48 hours thinking you're being "cautious"—the evidence window is 24-48 hours, and delays reduce efficacy. 1
- Do not use doses lower than 160 mg acutely (such as 81 mg) as these have not been proven effective for acute stroke treatment. 5, 6
- Do not continue high-dose aspirin (>100 mg) long-term after the acute phase—this increases bleeding risk without additional benefit. 2, 3
- Do not assume "more is better"—doses above 325 mg provide no additional benefit and increase adverse effects. 3, 7