What is the recommended dose of antiplatelets, such as aspirin (acetylsalicylic acid) and P2Y12 inhibitors like clopidogrel, for a patient with a history of ischemic stroke?

Recommended Antiplatelet Dosing After Ischemic Stroke

For patients with acute ischemic stroke, administer aspirin 160-325 mg as a loading dose within 24-48 hours after excluding intracranial hemorrhage, followed by 75-100 mg daily for long-term secondary prevention. 1, 2

Acute Phase Management (First 24-48 Hours)

Standard Ischemic Stroke

• Administer aspirin 160-325 mg as a single loading dose after brain imaging excludes hemorrhage 3, 1, 2
• Timing is critical: initiate within 24-48 hours of symptom onset for maximum benefit 3, 4
• If IV alteplase (tPA) was given, delay aspirin administration until 24 hours post-thrombolysis to minimize hemorrhagic risk 1, 2
• Avoid enteric-coated aspirin for loading dose due to delayed absorption 3, 5

Minor Stroke or High-Risk TIA (ABCD2 Score ≥4)

• Initiate dual antiplatelet therapy (DAPT) within 12-24 hours of symptom onset: 1, 5
  • Aspirin loading dose: 160-325 mg 1, 5
  • Plus clopidogrel loading dose: 300-600 mg 1, 6
• Continue with aspirin 75-100 mg daily plus clopidogrel 75 mg daily for exactly 21 days 1, 5
• After 21 days, transition to single antiplatelet therapy 1
• Recent evidence supports extending this window up to 72 hours with similar benefit 7

Alternative Routes for Dysphagia

• Rectal aspirin 325 mg daily if oral administration not possible 1, 2, 5
• Enteral tube aspirin 81 mg daily as alternative 1, 2

Long-Term Maintenance Therapy (Beyond 21-30 Days)

First-Line Options (All Class I Recommendations)

Choose one of the following regimens: 3

1. Aspirin 75-100 mg daily (most commonly recommended dose range) 3, 1, 4

   • Doses of 50-325 mg daily are acceptable per guidelines 3
   • Higher doses (>100 mg) increase bleeding risk without additional benefit 1

2. Clopidogrel 75 mg daily (equally effective alternative to aspirin) 3, 6, 4

   • Preferred for patients with aspirin allergy or intolerance 3
   • No loading dose needed for long-term maintenance 6

3. Aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily 3, 4

   • Suggested over aspirin alone based on direct comparison trials 3
   • May cause persistent headache limiting tolerability 3

Critical Dosing Considerations

Avoid these common pitfalls:

• Do NOT continue dual antiplatelet therapy (aspirin + clopidogrel) beyond 21-30 days in stable patients, as this significantly increases major hemorrhage risk (HR 2.22-2.32) without additional benefit 1
• Do NOT use aspirin plus clopidogrel for routine long-term secondary prevention 3, 4
• Do NOT increase aspirin dose if stroke occurs while on aspirin - instead, switch to alternative antiplatelet agent 3
• Do NOT discontinue antiplatelet therapy unless contraindicated or switching to anticoagulation for cardioembolic etiology 1

Special Populations

Extracranial Carotid or Vertebral Atherosclerosis

• Aspirin 75-325 mg daily, clopidogrel 75 mg daily, or aspirin/extended-release dipyridamole combination are all acceptable 3

Cardioembolic Stroke (Atrial Fibrillation)

• Oral anticoagulation is required instead of antiplatelet therapy for patients with CHA2DS2-VASc score ≥2 in males or ≥3 in females 3, 1, 4
• If anticoagulation is contraindicated, use aspirin 325 mg daily 5

Peripheral Arterial Disease with Stroke

• Aspirin 75-325 mg daily or clopidogrel 75 mg daily 3

Evidence Quality and Guideline Support

The recommendation for early aspirin in acute ischemic stroke is supported by Grade 1A evidence from two large randomized controlled trials (IST and CAST) involving over 40,000 patients, demonstrating 13 fewer deaths or dependencies per 1,000 patients treated 3, 8, 4

The dual antiplatelet therapy recommendation for minor stroke/high-risk TIA is based on multiple trials showing consistent benefit when initiated within 24-72 hours, with hazard ratios of 0.70-0.85 for stroke prevention 1, 7

Continue antiplatelet therapy indefinitely for lifelong secondary prevention unless contraindications develop 1, 2