What is the recommended loading dose of Dual Antiplatelet Therapy (DAPT) for patients with acute ischemic stroke?

Loading Dose of DAPT in Acute Ischemic Stroke

For patients with minor ischemic stroke (NIHSS ≤3-5) or high-risk TIA (ABCD2 ≥4), administer loading doses of aspirin 160-325 mg PLUS clopidogrel 300-600 mg within 12-24 hours of symptom onset, after excluding intracranial hemorrhage on neuroimaging. 1, 2, 3

Patient Selection for DAPT Loading

Eligible patients include:

• Minor ischemic stroke with NIHSS ≤3-5 1, 2
• High-risk TIA with ABCD2 score ≥4 1, 2
• Noncardioembolic mechanism 2
• Presenting within 24 hours of symptom onset 2

Specific Loading Dose Regimens

Aspirin + Clopidogrel Regimen (Preferred)

• Aspirin loading dose: 160-325 mg (based on CHANCE and POINT trials) 1, 2, 3
• Clopidogrel loading dose: 300 mg (CHANCE trial) OR 600 mg (POINT trial) 1, 2, 3
• Maintenance: Continue aspirin 81 mg daily + clopidogrel 75 mg daily for exactly 21 days 1, 2
• After 21 days: Switch to single antiplatelet therapy (aspirin 81 mg daily OR clopidogrel 75 mg daily) 1, 2

Alternative: Aspirin + Ticagrelor Regimen

• Aspirin loading dose: 300-325 mg 1
• Ticagrelor loading dose: 180 mg 1
• Maintenance: Continue aspirin 75-100 mg daily + ticagrelor 90 mg twice daily for 30 days 1
• After 30 days: Switch to single antiplatelet therapy 1

Critical Timing Considerations

The loading dose must be administered:

• Within 12-24 hours of symptom onset for maximum benefit 1, 2
• Only AFTER intracranial hemorrhage is excluded on neuroimaging 1, 2, 3
• If IV alteplase was given, delay aspirin until 24 hours post-thrombolysis 2, 3

Rationale for loading doses: Standard clopidogrel 75 mg daily takes approximately 5 days to achieve maximal platelet inhibition, whereas loading doses provide immediate antiplatelet effect 2, 3

Evidence Supporting Short-Duration DAPT

The benefit of DAPT is time-dependent and duration-limited:

• Maximum efficacy: Short-duration DAPT (≤1 month) started early reduces recurrent stroke by 24-26% compared to aspirin alone 4, 5, 6
• Bleeding risk increases with duration: DAPT beyond 90 days significantly increases major hemorrhage risk (HR 2.22-2.32) without additional benefit 2, 4, 5
• Optimal duration: 21 days maximizes efficacy while minimizing bleeding risk 2, 4

Safety Profile and Monitoring

Expected bleeding risks with DAPT:

• Major bleeding increases by approximately 2-fold (RR 1.88-2.22) 4, 5, 6
• Number needed to harm for major bleeding: 113-258 patients 4
• Intracranial hemorrhage risk increases (RR 1.55-1.77) 4, 5

However, the absolute benefits substantially outweigh bleeding risks in high-risk patients 2

Common Pitfalls to Avoid

• Do NOT use enteric-coated aspirin for loading dose - it has slower onset of action 2, 3
• Do NOT continue DAPT beyond 21-30 days - bleeding risk outweighs benefit after this period 2, 4
• Do NOT administer loading doses before excluding intracranial hemorrhage on neuroimaging 1, 2, 3
• Do NOT use DAPT in patients with moderate-severe stroke (NIHSS >5) - only indicated for minor stroke/high-risk TIA 1, 2
• Do NOT delay proven therapies - DAPT is NOT a substitute for thrombolysis or mechanical thrombectomy in eligible patients 2

Alternative Routes for Patients Unable to Swallow

• Rectal aspirin 325 mg daily 1, 2, 3
• Aspirin 81 mg daily via enteral tube 1, 2
• Clopidogrel 75 mg daily via enteral tube 1

For Patients NOT Meeting DAPT Criteria

For patients with moderate-severe stroke or those not meeting high-risk criteria:

• Administer aspirin 160-325 mg as a single loading dose only 1, 2, 7
• Continue with aspirin 75-100 mg daily for long-term secondary prevention 2
• Alternative: Clopidogrel 75 mg daily (equally effective) 2