What is the next best step in management for a patient with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score of 3, hemispatial neglect, and hemiparesis with power 4/5: thrombolysis or Dual Antiplatelet Therapy (DAPT)?

Management of Acute Ischemic Stroke with NIHSS Score of 3

For this patient with acute ischemic stroke, NIHSS score of 3, hemispatial neglect, and hemiparesis (power 4/5), dual antiplatelet therapy (DAPT) with aspirin and clopidogrel for 21-30 days is the recommended treatment, NOT thrombolysis. 1

Why DAPT is Preferred Over Thrombolysis in This Case

NIHSS Score of 3 Defines Minor Stroke

• An NIHSS score of 3 qualifies as a minor stroke (NIHSS 0-3), which is specifically the population where DAPT has demonstrated superior outcomes. 1
• The 2018 AHA/ASA guidelines explicitly recommend DAPT for minor stroke patients with NIHSS ≤3, with a Class IIa, Level B-R recommendation. 1
• The Canadian Stroke Best Practice Recommendations (2018) provide a Class A recommendation for DAPT in minor stroke (NIHSS 0-3) of noncardioembolic origin. 1

Evidence Against Thrombolysis in Minor Stroke

• Thrombolysis in patients with NIHSS scores of 0-2 does NOT improve 90-day functional outcomes and actually increases the risk of symptomatic intracranial hemorrhage (sICH). 2
• While thrombolysis shows benefit in patients with NIHSS 3-5, the absolute benefit is modest compared to the hemorrhagic risk, particularly when DAPT offers a safer alternative with proven efficacy. 2
• The original NINDS trial data showed that patients with mild-to-moderate strokes (NIHSS <20) had better outcomes, but this included a broad range, and subsequent evidence has refined recommendations for the mildest strokes. 1

DAPT Protocol for This Patient

Immediate Loading Dose:

• Clopidogrel 300-600 mg PLUS aspirin 160 mg should be administered immediately after brain imaging excludes hemorrhage and dysphagia screening is passed. 1
• Treatment must be initiated within 24 hours of symptom onset, ideally within 12 hours. 1

Maintenance Therapy:

• Continue clopidogrel 75 mg daily PLUS aspirin 81-325 mg daily for exactly 21-30 days. 1
• After 21-30 days, switch to antiplatelet monotherapy (either aspirin or clopidogrel alone) indefinitely. 1

Supporting Evidence for DAPT in Minor Stroke

• The POINT trial demonstrated that DAPT in patients with minor stroke (NIHSS 0-3) or high-risk TIA significantly reduced recurrent stroke at 90 days compared to aspirin alone. 1
• A 2024 Chinese trial (ATAMIS) showed that among patients with mild to moderate stroke, DAPT reduced early neurologic deterioration at 7 days (4.8% vs 6.7%, p=0.03) with similar bleeding rates. 3
• Meta-analysis of 16 RCTs with 29,032 patients confirmed that short-duration DAPT (≤1 month) started during the acute phase reduces recurrent stroke without the increased bleeding risk seen with longer-duration DAPT. 4

Critical Pitfalls to Avoid

Do NOT Give Thrombolysis Based on Symptom Severity Alone

• The presence of "disabling" symptoms like hemispatial neglect does not automatically warrant thrombolysis in a patient with NIHSS ≤3. The evidence-based approach prioritizes the validated NIHSS score over subjective assessment of disability. 1
• Historical concerns about "rapidly improving" symptoms as a contraindication have been challenged, but for NIHSS ≤3, DAPT remains the evidence-based choice. 1

Timing is Critical for DAPT

• DAPT must be started within 24 hours of symptom onset to achieve maximum benefit. 1
• Ideally, treatment should begin in the emergency department before discharge. 1

Do NOT Continue DAPT Beyond 30 Days

• Extending DAPT beyond 21-30 days increases bleeding risk (intracranial bleeding RR 1.55, major bleeding RR 1.90) without additional stroke prevention benefit. 4
• The number needed to harm for intracranial bleeding with prolonged DAPT is 258, and for major bleeding is 113. 4

Pre-existing Antiplatelet Use

• If this patient was already on aspirin or clopidogrel monotherapy, they should still receive the loading dose of the second agent to achieve DAPT. 1
• However, if a patient were already on DAPT (aspirin + clopidogrel), this would be a relative contraindication to thrombolysis due to increased hemorrhagic risk. 5

When Thrombolysis WOULD Be Appropriate

Thrombolysis should be considered in mild stroke patients with NIHSS 3-5 IF:

• The patient has a documented large vessel occlusion on vascular imaging. 1
• There are concerns about potential for significant deterioration based on vascular territory at risk. 1
• The patient cannot receive or has contraindications to DAPT. 1

However, even in these scenarios, the 2018 guidelines favor DAPT for NIHSS ≤3, making thrombolysis a secondary consideration. 1

Monitoring and Follow-up

• Assess for GI bleeding risk, as DAPT increases extracranial bleeding (0.9% vs 0.4% in POINT trial). 1
• Consider GI protection with proton pump inhibitors in high-risk patients. 1
• Ensure patient understands to stop one antiplatelet agent after 21-30 days and continue monotherapy indefinitely. 1
• Screen for cardioembolic source, as presence of atrial fibrillation would change management to anticoagulation rather than antiplatelet therapy. 1