What is the role of aspirin (acetylsalicylic acid) in the management of Kawasaki disease?

Role of Aspirin in Kawasaki Disease Management

Aspirin plays a critical role in Kawasaki disease management as an antiplatelet agent, with low-dose aspirin (3-5 mg/kg/day) being non-inferior to high-dose aspirin for preventing coronary artery abnormalities when used in conjunction with IVIG. 1, 2

Aspirin Therapy in Acute Phase Management

Dosing Considerations

• Initial dosing options:

  • Low-dose (3-5 mg/kg/day): Focuses on antiplatelet effects
  • High-dose (80 mg/kg/day): Provides both anti-inflammatory and antiplatelet effects
  • Recent evidence shows no significant benefit of high-dose over low-dose aspirin in preventing coronary artery abnormalities 2, 3

• Duration of therapy:

  • Continue aspirin until 6-8 weeks after disease onset if no coronary abnormalities develop
  • Continue indefinitely if coronary artery abnormalities are present 1

Evidence for Aspirin Dosing

• A 2017 multicenter study of 1,213 patients demonstrated that low-dose aspirin was not inferior to high-dose aspirin for reducing coronary artery abnormalities when used with IVIG 2
• A 2024 nationwide Japanese cohort study of 82,109 patients found no significant benefit in coronary outcomes with aspirin doses above 30 mg/kg/day 4
• Duration of high-dose aspirin therapy does not affect long-term coronary artery outcomes 5

Role in Preventing Thrombosis in Patients with Coronary Disease

• Platelet activation is a significant component throughout all phases of Kawasaki disease, making antiplatelet therapy essential 6
• For patients with mild and stable disease, low-dose aspirin alone may be appropriate 6
• As coronary artery enlargement increases in severity:
  • Consider combination therapy with aspirin plus other antiplatelet agents (clopidogrel, dipyridamole) 6
  • For rapidly expanding coronary aneurysms with high thrombosis risk, consider heparin with aspirin 6

Management of Aspirin Allergies or Contraindications

• For patients with documented aspirin allergy, clopidogrel at 1 mg/kg/day (up to 75 mg) is the preferred alternative 1
• Continue clopidogrel for the same duration as would be recommended for aspirin therapy 1

Important Considerations and Precautions

Reye Syndrome Prevention

• Annual inactivated influenza vaccination is recommended for all children on long-term aspirin therapy 1
• Only inactivated vaccines should be administered to children on aspirin therapy 1
• Family members should also be vaccinated to reduce transmission risk 1

Monitoring

• Regular echocardiographic follow-up is essential for patients on aspirin therapy 1
• Monitor for bleeding complications, particularly with higher doses

Treatment Algorithm

1. Initial treatment:

   • IVIG 2 g/kg as a single infusion over 10-12 hours
   • Aspirin 3-5 mg/kg/day (low-dose) is sufficient when used with IVIG

2. For patients with IVIG resistance:

   • Consider second dose of IVIG 2 g/kg
   • Consider adding corticosteroids, which have been shown to reduce coronary aneurysm formation when added to aspirin-containing regimens 7

3. Adjust aspirin therapy based on coronary status:

   • No coronary abnormalities: Continue aspirin for 6-8 weeks
   • With coronary abnormalities: Continue aspirin indefinitely
   • For large or multiple aneurysms: Consider combination therapy with aspirin plus anticoagulation 6, 1

The evidence clearly demonstrates that low-dose aspirin is as effective as high-dose aspirin for preventing coronary artery abnormalities in Kawasaki disease when used with IVIG, while potentially reducing side effects associated with high-dose therapy.