In an adult with a minor ischemic stroke (NIH Stroke Scale ≤ 3) or high‑risk transient ischemic attack presenting within 72 hours and no contraindications, should dual antiplatelet therapy with clopidogrel and aspirin be initiated, and what dosing and duration are recommended?

Dual Antiplatelet Therapy for Minor Stroke and High-Risk TIA

For adults with minor ischemic stroke (NIHSS ≤3) or high-risk TIA presenting within 72 hours, initiate dual antiplatelet therapy with clopidogrel plus aspirin within 24 hours of symptom onset (ideally within 12 hours), continue for exactly 21 days, then transition to single antiplatelet therapy indefinitely. 1, 2

Patient Selection Criteria

You should initiate dual antiplatelet therapy (DAPT) if ALL of the following are met:

• Minor ischemic stroke with NIHSS ≤3 OR high-risk TIA with ABCD2 score ≥4 1, 2
• Presentation within 72 hours of symptom onset (ideally within 24 hours) 1, 3
• Intracranial hemorrhage excluded on neuroimaging 1, 2
• No contraindications to antiplatelet therapy (no active bleeding, no recent major hemorrhage, no severe thrombocytopenia) 1, 2
• Did not receive IV alteplase within the past 24 hours 1

Loading Dose Protocol

Administer the following loading doses as soon as eligibility is confirmed:

• Clopidogrel 300-600 mg (300 mg per CHANCE trial, 600 mg per POINT trial) 1, 2, 4
• Aspirin 160-325 mg 1, 2

The 300 mg clopidogrel loading dose is adequate and was used successfully in the CHANCE trial, while 600 mg was used in POINT; both are acceptable, though 300 mg may reduce bleeding risk slightly. 4, 3

Maintenance Dosing (Days 2-21)

Continue the following daily doses for exactly 21 days:

• Clopidogrel 75 mg daily 1, 2, 4
• Aspirin 81-100 mg daily 1, 2

Duration: Exactly 21 Days

Stop DAPT at day 21 and transition to single antiplatelet therapy. 1, 2, 5

The benefit of DAPT is confined entirely to the first 21 days after stroke onset. 5 From day 22 to day 90, there is no additional stroke prevention benefit, but bleeding risk increases substantially with hazard ratios of 2.08-2.22 for major hemorrhage. 6, 3 Continuing DAPT beyond 21-30 days causes more harm than benefit. 6, 5

Transition to Long-Term Therapy (After Day 21)

Switch to single antiplatelet therapy indefinitely with one of the following options:

• Aspirin 75-100 mg daily (first-line recommendation) 1, 2
• Clopidogrel 75 mg daily (equally effective alternative, preferred if aspirin-intolerant) 1, 2
• Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily (alternative option) 1, 2

Evidence Supporting This Approach

The pooled analysis of CHANCE and POINT trials (10,051 patients) demonstrated that clopidogrel-aspirin reduced major ischemic events from 9.1% to 6.5% at 90 days (HR 0.70,95% CI 0.61-0.81, P<0.001), with the benefit occurring almost entirely within the first 21 days (HR 0.66,95% CI 0.56-0.77). 5 The most recent INSPIRES trial (2023) extended the treatment window to 72 hours and confirmed efficacy (HR 0.79,95% CI 0.66-0.94, P=0.008), though with increased moderate-to-severe bleeding (0.9% vs 0.4%, HR 2.08). 3

Critical Timing Considerations

Initiate DAPT as early as possible:

• Optimal window: Within 12-24 hours of symptom onset 1, 2
• Acceptable window: Up to 72 hours, though efficacy may be reduced 3
• After 72 hours: Use single antiplatelet therapy only 1

The earlier DAPT is initiated, the greater the stroke prevention benefit, as most recurrent strokes occur within the first week. 5, 4

Common Pitfalls to Avoid

Do NOT use DAPT if:

• Patient received IV alteplase within the past 24 hours (wait 24 hours post-thrombolysis before starting antiplatelet therapy) 1
• NIHSS >3 (use single antiplatelet therapy instead) 1, 2
• Intracranial hemorrhage has not been ruled out on imaging 1, 2

Do NOT continue DAPT beyond 21 days unless there is a separate cardiac indication (e.g., recent drug-eluting stent), as this significantly increases bleeding risk without reducing stroke recurrence. 6, 5

Do NOT use ticagrelor instead of clopidogrel in this setting, as ticagrelor is not recommended over aspirin for acute minor stroke treatment. 1

Do NOT substitute DAPT for thrombolysis or thrombectomy in eligible patients, as antiplatelet therapy is not a replacement for acute reperfusion therapy. 1

Special Populations

For patients with dysphagia or impaired swallowing:

• Administer clopidogrel 75 mg + aspirin 81 mg via enteral tube, OR
• Use aspirin 325 mg rectal suppository daily 1, 2

For patients ≥70 years:

• No dose adjustment needed; COMMIT trial data showed no excess bleeding risk with age in this population 7

For patients presenting between 24-72 hours:

• DAPT is still beneficial based on INSPIRES trial data, though the treatment effect may be slightly attenuated compared to <24 hour initiation 3