What is the recommended antiplatelet therapy for a patient with an ischemic stroke, as indicated by the National Institutes of Health Stroke Scale (NIHSS) score, and a history of coronary artery disease or coronary stenting?

Dual Antiplatelet Therapy for Ischemic Stroke Based on NIHSS Score

Primary Recommendation

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

NIHSS-Based Treatment Algorithm

Minor Stroke (NIHSS ≤3) or High-Risk TIA (ABCD2 ≥4)

Loading Dose (within 12-24 hours):

• Aspirin 160-325 mg PLUS clopidogrel 300-600 mg 1, 2
• Must exclude intracranial hemorrhage on neuroimaging first 1, 2

Maintenance Phase (21 days):

• Aspirin 81 mg daily PLUS clopidogrel 75 mg daily 1, 2
• This reduces recurrent ischemic stroke by 25-32% compared to single antiplatelet therapy 2

After 21 Days:

• Switch to single antiplatelet therapy: aspirin 75-100 mg daily OR clopidogrel 75 mg daily indefinitely 1, 2

Mild-Moderate Stroke (NIHSS ≤5) - Alternative Regimen

Loading Dose:

• Aspirin 300-325 mg PLUS ticagrelor 180 mg within 24 hours 1

Maintenance Phase (30 days):

• Aspirin 75-100 mg daily PLUS ticagrelor 90 mg twice daily 1

After 30 Days:

• Transition to single antiplatelet therapy 1

Moderate-to-Severe Stroke (NIHSS >3)

Single Antiplatelet Therapy Only:

• Aspirin 160-325 mg loading dose within 48 hours 1
• Maintenance: aspirin 75-100 mg daily OR clopidogrel 75 mg daily 1
• Do NOT use DAPT - increased bleeding risk without proven benefit in this population 2

Special Consideration: Coronary Artery Disease or Recent Stenting

This is a critical clinical scenario where stroke and cardiac guidelines intersect. If the patient has recent acute coronary syndrome or coronary stenting, DAPT may need to be continued for up to 12 months following cardiology guidelines, NOT the 21-day stroke protocol. 2 However, this creates a challenging balance between stroke recurrence prevention and bleeding risk.

For patients with stable coronary disease (no recent ACS or stenting):

• Follow the standard stroke DAPT protocol above (21 days for minor stroke) 2
• The presence of stable CAD alone does not justify prolonged DAPT beyond 21 days 2

For patients with recent coronary stenting (<12 months):

• Continue DAPT as per cardiology guidelines (typically 6-12 months) 2
• This takes precedence over the 21-day stroke protocol 2

Critical Timing and Safety Considerations

Absolute Requirements Before Starting DAPT:

• Intracranial hemorrhage must be excluded on neuroimaging 1, 2
• If IV alteplase was given, delay DAPT until 24 hours post-thrombolysis 2
• Presentation must be within 24 hours of symptom onset for optimal benefit 1, 2

Do NOT Use DAPT If:

• NIHSS >5 (use single antiplatelet therapy instead) 2
• Presentation >24 hours after symptom onset 2
• High bleeding risk conditions present 2
• Patient received thrombolysis within past 24 hours 2

Common Pitfalls to Avoid

Never continue DAPT beyond 21-30 days in stroke patients without cardiac indications - this significantly increases major hemorrhage risk (RR 2.22-2.32) without additional stroke prevention benefit. 2 The benefit-to-risk ratio only favors DAPT during the first 21 days. 2

Do not use DAPT as a substitute for thrombolysis or mechanical thrombectomy in eligible patients - this delays definitive treatment and worsens outcomes. 2

Avoid enteric-coated aspirin for loading doses - it has slower onset of action and delays therapeutic effect. 2

For patients with dysphagia: Administer rectal aspirin 325 mg daily or aspirin 81 mg plus clopidogrel 75 mg via enteral tube. 1, 2

Evidence Quality and Guideline Strength

The recommendation for DAPT in minor stroke (NIHSS ≤3) is supported by high-quality evidence (Class I, Level A) from multiple large randomized trials including CHANCE and POINT. 1, 2 The 2023 World Stroke Organization guidelines provide the most current synthesis of this evidence. 1

For patients with moderate-to-severe stroke, the 2012 CHEST guidelines recommend against routine DAPT (Grade 1B), favoring single antiplatelet therapy with aspirin 160-325 mg within 48 hours (Grade 1A). 1