What is the recommended dose and duration of a single antiplatelet agent, such as aspirin (acetylsalicylic acid), for the management of ischemic stroke?

Recommended Dose and Duration of Single Antiplatelet Therapy for Ischemic Stroke

Administer aspirin 160-325 mg as a loading dose within 24-48 hours of acute ischemic stroke onset (after excluding intracranial hemorrhage), then continue with 75-100 mg daily for long-term secondary prevention. 1

Acute Phase Dosing (First 24-48 Hours)

Loading Dose

• Aspirin 160-325 mg should be given as a single loading dose to achieve rapid and complete inhibition of thromboxane A2-dependent platelet aggregation 1, 2
• The American Heart Association specifically supports doses between 160-300 mg based on large clinical trial data involving over 40,000 patients 1
• This loading dose strategy is critical because standard 75 mg daily dosing does not produce maximal platelet inhibition for approximately 5 days 1

Timing Considerations

• Initiate aspirin within 24-48 hours of stroke onset for maximum benefit, as efficacy is time-dependent 1, 3
• If IV alteplase (tPA) was administered, delay aspirin until 24 hours post-thrombolysis to minimize hemorrhagic risk 1
• Intracranial hemorrhage must be ruled out on neuroimaging before starting antiplatelet therapy 1

Route of Administration

• Oral administration is preferred if the patient can swallow safely 2
• For patients with impaired swallowing, rectal aspirin 325 mg daily or aspirin 81 mg daily via enteral tube are reasonable alternatives 1
• Avoid enteric-coated aspirin for the loading dose as it has a slower onset of action 1

Long-Term Maintenance Dosing

Standard Maintenance Therapy

• Continue with aspirin 75-100 mg daily for long-term secondary prevention after the acute phase 1, 4
• Doses between 50-325 mg daily have been shown effective in secondary prevention, though doses >150 mg per day are associated with worse gastrointestinal tolerance 5
• The risk of major bleeding with 160 mg/day is the same as with 80 mg/day (1-2 cases per 1000 patient-years), and fatal bleeding risk is equivalent 6

Duration of Therapy

• Antiplatelet therapy should be continued indefinitely for secondary stroke prevention 4, 5
• The primary benefit is prevention of recurrent ischemic events rather than limiting neurological consequences of the acute stroke itself 7

Special Population: Minor Stroke or High-Risk TIA

Dual Antiplatelet Therapy (DAPT) Instead of Monotherapy

• For patients with minor ischemic stroke or high-risk TIA, initiate dual antiplatelet therapy with aspirin 160-325 mg PLUS clopidogrel 300-600 mg as loading doses 1, 8
• Continue with aspirin 81 mg daily plus clopidogrel 75 mg daily for exactly 21 days (maximum 30 days) 1, 8
• Then transition to single antiplatelet therapy (aspirin 81 mg daily or clopidogrel 75 mg daily) 8
• DAPT should be initiated as early as possible, ideally within 12-24 hours of symptom onset 1, 8

Evidence Quality and Clinical Impact

The recommendation for early aspirin is supported by Grade 1A evidence from two large randomized controlled trials demonstrating 13 fewer deaths or dependencies per 1000 patients treated (number needed to treat = 79) 1, 3. The absolute benefits substantially outweigh the absolute risks of major bleeding in moderate to high-risk patients 1.

Critical Pitfalls to Avoid

• Do NOT use aspirin as a substitute for thrombolysis or mechanical thrombectomy in eligible patients, as this delays definitive treatment and worsens outcomes 1
• Do NOT delay aspirin beyond 48 hours, as maximum efficacy occurs when started early 1
• Do NOT use glycoprotein IIb/IIIa inhibitors (such as abciximab), as these are potentially harmful in acute ischemic stroke 1
• Do NOT use the combination of aspirin and clopidogrel for routine ischemic stroke (only for minor stroke/high-risk TIA), as it does not reduce vascular events and increases life-threatening bleeding 5