When to initiate dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in patients with acute ischemic stroke?

When to Initiate Dual Antiplatelet Therapy in Acute Ischemic Stroke

For patients with minor acute ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4), initiate dual antiplatelet therapy with aspirin plus clopidogrel within 24 hours of symptom onset (ideally within 12-24 hours), continue for 21-30 days, then switch to single antiplatelet therapy. 1, 2

Timing of Initiation

Start DAPT as early as possible, ideally within 12-24 hours of symptom onset:

• The therapeutic window extends up to 72 hours after symptom onset, with consistent benefit demonstrated across this entire timeframe 3, 4
• Patients randomized within 24 hours, 24-48 hours, and 48-72 hours all showed similar relative risk reductions for recurrent stroke (HR 0.83,0.85, and 0.70 respectively, with no significant interaction) 4
• Earlier initiation (within 24 hours) appears optimal based on the original CHANCE trial data, though benefit persists with later initiation 1

Specific Eligibility Criteria

Use DAPT only in patients meeting ALL of the following:

• Minor stroke severity: NIHSS score ≤3 1, 2
• High-risk TIA: ABCD2 score ≥4 1, 2
• Non-cardioembolic mechanism: Presumed atherosclerotic cause 3
• No contraindications: No history of intracranial hemorrhage, no planned thrombolysis or thrombectomy, acceptable bleeding risk 3

Dosing Regimen

Loading dose on Day 1:

• Aspirin 160-325 mg PLUS clopidogrel 300-600 mg 2

Maintenance dose Days 2-21:

• Aspirin 81-100 mg daily PLUS clopidogrel 75 mg daily 1, 2

After 21-30 days:

• Switch to single antiplatelet therapy (aspirin 81 mg daily OR clopidogrel 75 mg daily) indefinitely 1, 2

Duration: The Critical 21-30 Day Window

Do NOT continue DAPT beyond 21-30 days in most patients:

• Meta-analyses demonstrate that bleeding risk begins to outweigh benefit as early as 21 days 1
• The number needed to treat to prevent one stroke is 92, while the number needed to harm for severe bleeding is 263 1
• Major bleeding risk increases significantly with DAPT (RR 2.22,95% CI 1.14-4.34) 5
• Long-term DAPT (beyond 90 days) shows no benefit over single antiplatelet therapy and significantly increases intracranial hemorrhage and major bleeding 1

Exception for intracranial atherosclerosis:

• For patients with severe stenosis (50-99%) of a major intracranial artery, DAPT for up to 90 days is reasonable 1

When to Use Aspirin Monotherapy Instead

Use single antiplatelet therapy (NOT DAPT) in:

• Moderate to severe stroke: NIHSS >3 2
• Low-risk TIA: ABCD2 score <4 2
• Delayed presentation: >24 hours after symptom onset (though recent evidence suggests benefit up to 72 hours, guideline recommendations prioritize early initiation) 1
• High bleeding risk: History of gastrointestinal bleeding, concurrent anticoagulation need, coagulopathy 2
• Cardioembolic stroke: These patients require anticoagulation, not DAPT 1

Safety Monitoring

Key bleeding risks to monitor:

• Moderate-to-severe bleeding occurs in approximately 0.9% of DAPT patients vs 0.4% with aspirin alone 3, 4
• Older patients and those with more severe strokes have higher ICH risk with DAPT 1
• Consider proton pump inhibitor co-prescription for patients with gastrointestinal bleeding risk factors 2
• Discontinuation rates due to bleeding are approximately 2.8% with DAPT vs 0.6% with aspirin alone 1

Common Pitfalls to Avoid

Do not:

• Continue DAPT indefinitely—this significantly increases bleeding without additional benefit 1
• Use DAPT in patients with large strokes or those at high risk for hemorrhagic transformation 1
• Initiate DAPT in patients who received thrombolysis or thrombectomy 3
• Use triple antiplatelet therapy (aspirin + clopidogrel + dipyridamole)—this increases bleeding without improving outcomes 1

Efficacy Data

DAPT reduces recurrent stroke by:

• 26% relative risk reduction for any stroke (RR 0.74,95% CI 0.67-0.83) 6
• 28% relative risk reduction for ischemic stroke (RR 0.72,95% CI 0.65-0.80) 6
• 24% relative risk reduction for major adverse cardiovascular events (RR 0.76,95% CI 0.68-0.84) 6
• Absolute risk reduction of approximately 2% for recurrent stroke at 90 days 1, 5