What is the recommended treatment for patients with Embolic Stroke of Undetermined Source (ESUS)?

Treatment for Embolic Stroke of Undetermined Source (ESUS)

For patients with Embolic Stroke of Undetermined Source (ESUS), antiplatelet therapy is recommended over oral anticoagulation for secondary stroke prevention. 1

Definition and Approach to ESUS

ESUS refers to non-lacunar ischemic strokes without an identified source despite standard diagnostic evaluation. These strokes account for approximately 9-25% of all ischemic strokes and carry a significant risk of recurrence.

Diagnostic Workup

• Prolonged cardiac monitoring is recommended to detect occult atrial fibrillation 1
• Complete vascular imaging to rule out significant stenosis
• Echocardiography to evaluate for cardiac sources
• Laboratory testing to exclude hypercoagulable states

Evidence-Based Treatment Algorithm

First-Line Treatment

• Single antiplatelet therapy (SAPT) is the mainstay of treatment for ESUS 1
  • Options include:
    • Aspirin 50-325 mg daily
    • Clopidogrel 75 mg daily
    • Combination of aspirin 25 mg and extended-release dipyridamole 200 mg twice daily

For Recent ESUS (within 24 hours to 7 days)

• Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel should be initiated early and continued for 21-90 days, followed by SAPT 1
  • This applies to patients with minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4)
  • DAPT should be initiated ideally within 12-24 hours but at least within 7 days of symptom onset

Important Cautions

• Oral anticoagulation is NOT recommended for ESUS patients without documented atrial fibrillation 1
  • Multiple randomized controlled trials have shown no benefit of DOACs over antiplatelet therapy in ESUS 2, 3
  • Increased bleeding risk with anticoagulation without improved efficacy 3
• DAPT beyond 90 days is associated with excess bleeding risk without additional benefit 1

Monitoring for Atrial Fibrillation

• Prolonged cardiac monitoring is essential in ESUS patients to detect occult atrial fibrillation 1
• If atrial fibrillation is detected, treatment should be switched to oral anticoagulation
• The probability of AF detection increases with longer monitoring duration, from 2% at 1 week to over 20% by 3 years 1

Special Considerations

Age-Related Differences

• Recent meta-analysis suggests patients aged ≥75 years may benefit more from DOACs than younger patients (RR 0.76,95% CI 0.60-0.97) 2
• However, current guidelines do not recommend different treatment based on age alone

Timing of Treatment

• Starting anticoagulation ≥8 days after index stroke may be more beneficial than earlier initiation (RR 0.80,95% CI 0.66-0.97) 2
• However, this finding requires further validation before changing clinical practice

Common Pitfalls to Avoid

1. Premature anticoagulation: Do not start anticoagulation without documented atrial fibrillation
2. Inadequate monitoring: Failure to perform prolonged cardiac monitoring may miss occult AF
3. Prolonged DAPT: Continuing DAPT beyond 90 days increases bleeding risk without additional benefit
4. Incomplete workup: Ensure thorough evaluation for all potential embolic sources

Conclusion

The weight of evidence from multiple randomized controlled trials and current guidelines strongly supports antiplatelet therapy over anticoagulation for patients with ESUS. While ongoing research may help identify subgroups who might benefit from anticoagulation, current practice should follow the established guidelines of using antiplatelet therapy for secondary stroke prevention in ESUS.