What is the recommended antiplatelet therapy post stroke or Transient Ischemic Attack (TIA)?

Antiplatelet Therapy Post-Stroke or TIA

For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA, initiate dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel within 12-24 hours for 21 days, followed by long-term single antiplatelet therapy; for all other non-cardioembolic strokes, use long-term single antiplatelet therapy with clopidogrel, aspirin plus dipyridamole, or aspirin alone. 1

Acute Phase: Minor Stroke and High-Risk TIA

Dual Antiplatelet Therapy (DAPT) - First 21-30 Days

For minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4):

• Start aspirin 81 mg daily plus clopidogrel 75 mg daily within 12-24 hours after excluding intracranial hemorrhage on neuroimaging 1, 2
• Loading doses: Aspirin 160-325 mg plus clopidogrel 300-600 mg at initiation 1, 2
• Duration: Continue DAPT for exactly 21 days 1, 2, 3
• This regimen reduces stroke recurrence risk significantly compared to single antiplatelet therapy in the acute period 3

Alternative DAPT regimen (mild-moderate stroke, NIHSS ≤5):

• Aspirin 75-100 mg daily plus ticagrelor 90 mg twice daily for 30 days 1
• Loading doses: Aspirin 300-325 mg plus ticagrelor 180 mg 1
• This carries a weak recommendation based on moderate quality evidence 3

Critical Implementation Points

• Timing is essential: Initiate DAPT as early as possible, ideally within 12-24 hours of symptom onset 1, 2
• Mandatory neuroimaging: Must exclude intracranial hemorrhage before starting any antiplatelet therapy 1, 2
• Do not extend DAPT beyond 21-30 days in most patients, as prolonged dual therapy increases bleeding risk without additional benefit 4

Long-Term Secondary Prevention (After DAPT Period)

Single Antiplatelet Therapy Options

After completing the 21-day DAPT course, transition to one of these long-term options:

• Clopidogrel 75 mg daily (preferred first-line) 1, 5
• Aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily (equally preferred) 1, 5
• Aspirin 81-325 mg daily (acceptable alternative if above agents not tolerated) 1, 5

The 2023 World Stroke Organization guidelines recommend these three options as equivalent for long-term non-cardioembolic stroke prevention 1. Clopidogrel or aspirin/dipyridamole are preferred over aspirin monotherapy based on superior efficacy 5.

Special Clinical Scenarios

Intracranial Atherosclerotic Stenosis (50-99%)

• DAPT with aspirin plus clopidogrel is recommended for patients with moderate to high-grade intracranial atherosclerotic stenosis 1, 2
• Consider extended DAPT duration (up to 90 days) in this specific population 4
• Aggressive blood pressure control (target <140 mmHg systolic) and high-dose statin therapy are also mandatory 1

Patients Already on Aspirin Who Experience Stroke

• Switch to clopidogrel 75 mg daily or add dipyridamole to aspirin 5
• This represents treatment failure on aspirin monotherapy 5

Impaired Swallowing Mechanisms

• Rectal aspirin 325 mg daily, or aspirin 81 mg daily or clopidogrel 75 mg daily via enteral tube are reasonable alternatives 1

Embolic Stroke of Undetermined Source (ESUS)

• Use antiplatelet therapy, not anticoagulation 2
• Standard single antiplatelet options apply 1

Critical Exclusions: When NOT to Use Antiplatelet Therapy

Patients requiring anticoagulation should NOT receive antiplatelets for secondary stroke prevention: 1

• Atrial fibrillation (valvular or non-valvular) - use oral anticoagulation 1
• Mechanical heart valves - use warfarin (with aspirin added for mechanical mitral valves) 1
• Left ventricular or left atrial thrombus - use anticoagulation for at least 3 months 1

Common Pitfalls to Avoid

• Do not delay antiplatelet initiation - start immediately after excluding hemorrhage 5
• Do not continue DAPT beyond 21-30 days in typical minor stroke/TIA patients - bleeding risk outweighs benefit 4
• Do not use triple antiplatelet therapy - insufficient evidence of benefit with substantially increased bleeding complications 6
• Do not use anticoagulation for non-cardioembolic stroke unless there is a separate indication 5
• Do not forget the loading dose when initiating DAPT in the acute setting 1, 2

Monitoring Considerations

• Clopidogrel is preferred over ticlopidine due to fewer side effects and no need for routine blood monitoring 5
• Monitor for bleeding complications (bruising, gastrointestinal bleeding, intracranial hemorrhage) during DAPT 4
• Consider CYP2C19 polymorphism testing if clopidogrel resistance is suspected, though routine testing is not recommended 4