High-Dose Aspirin With IVIG Does Not Meaningfully Reduce Coronary Artery Lesions in Children With Kawasaki Disease

Author(s):

Luke Halpern, Assistant Editor

Key Takeaways

The trial found no significant difference in CAL outcomes between IVIG alone and IVIG with high-dose aspirin in KD patients.
High-dose aspirin may not be necessary in KD treatment, challenging traditional management practices.
Further research is needed to confirm these findings across diverse populations and optimize KD treatment strategies.

Though the rate of coronary artery lesions decreased across both cohorts of this trial of children with Kawasaki disease, there were no differences in lesion reduction between those receiving intravenous immunoglobulin (IVIG) alone and those receiving IVIG with aspirin.

Investigators of a randomized clinical trial (NCT02951234) that evaluated intravenous immunoglobulin (IVIG)-only treatment for patients with Kawasaki disease (KD) presenting with coronary artery lesions (CALs) found that the addition of high-dose aspirin did not play a meaningful role in managing CALs in this patient population. The results, which were published in the Journal of the American Medical Association, represent the first set of data from a multicenter, randomized trial investigating the combination of IVIG and aspirin in the acute stage of KD.^1,2

Aspirin, known for its anti-inflammatory effects, has been investigated for its use in Kawasaki disease. | Image Credit: © monticellllo - stock.adobe.com

Aspirin's Possible Role in Kawasaki Disease

KD, an acute vasculitis condition, can result in the development of CALs or coronary artery aneurysms, which are especially concerning developments for children. IVIG and aspirin can synergistically induce anti-inflammatory effects and are recommended by the American Heart Association. Specifically, prior studies have found that an IVIG dose of 2 g/kg per day is highly effective at minimizing the likelihood of CALs in KD.^1,3

To the knowledge of the current authors, there have been no prospective studies conducted to validate aspirin’s role in addressing inflammation associated with KD and diminishing CALs. In fact, in previously published research, investigators have proposed a significant correlation between the incidence of CALs and IVIG dosage, with aspirin being postulated to not have a meaningful influence on CAL reduction. Furthermore, some authors have observed cases of severe adverse effects associated with aspirin in children undergoing KD; this risk necessitates more thorough investigations of the role of aspirin in KD treatment.^1,3,4

Study Results Find No Difference Between IVIG-Aspirin and IVIG Alone

The current authors used patient clusters generated by Wang et al in a recent investigative study: a liver subgroup, a band subgroup, a node subgroup, and a young subgroup, with each group exhibiting differences in their response to treatment and outcomes of the disease. Their goal was to compare the treatment effectiveness for each subgroup of KD between the standard and test groups, with a primary study end point of CAL formation at 6 weeks following enrollment. A total of 152 patients diagnosed with KD were enrolled; 78 were assigned to the IVIG plus aspirin (standard) group and 74 were assigned to the IVIG-alone (intervention) group, according to the authors.^1,5

Ultimately, there were no significant differences observed between each of the groups in the frequency of coronary artery abnormalities during the study period (0.7 percentage points [95% CI, -4.5 to 5.8 percentage points]; P = .65). In a positive development, there was a major decrease in the frequency of CALs compared with baseline. The clusters determined by Wang et al were applied to the 2 study groups to assess the impact of high-dose aspirin in diverse populations. Upon this analysis, which included comparing overall CAL rates at baseline, 6 weeks, and 6 months, the authors found no significant differences between clusters within each group regarding their reduced rates of CAL development.^1,5

About the Trial

Trial Name: A Multi-center, Randomized to Compare the Efficacy of IVIG Alone and IVIG Plus High-dose Aspirin in Kawasaki Disease

ClinicalTrials.gov ID: NCT02951234

Sponsor: Chang Gung Memorial Hospital

Completion Date: August 2019

A statistical noninferiority comparison was also conducted, in which the CAL rate in the IVIG-alone group was found to be not higher by 10% than that in the IVIG plus aspirin group, which established noninferiority with clinical insignificance, according to the investigators. In a critical discovery, the authors also found that there was no major distinction between each group in C-reactive protein and platelet counts, 2 types of inflammatory biomarkers. The results from this trial can aid treatment providers in determining the proper dose of aspirin for children with KD receiving IVIG, or if aspirin is necessary at all.¹

“Future studies or similarly designed clinical trials in other race and ethnicity or geographic populations may be necessary to confirm the broad applicability of our findings,” the investigators concluded.¹

REFERENCES

1. Kuo HC, Lin MC, Kao CC, et al. Intravenous immunoglobulin alone for coronary artery lesion treatment of Kawasaki disease: A randomized clinical trial. JAMA Netw Open. 2025;8(4):e253063. doi:10.1001/jamanetworkopen.2025.3063

2. ClinicalTrials.gov. A Multi-center, Randomized to Compare the Efficacy of IVIG Alone and IVIG Plus High-dose Aspirin in Kawasaki Disease. National Library of Medicine. Last Updated March 6, 2018. Accessed April 8, 2025. https://clinicaltrials.gov/study/NCT02951234?term=NCT02951234&rank=1

3. Ksieh K-S, Weng K-P, Lin C-C, et al. Treatment of acute Kawasaki disease: Aspirin’s role in the febrile stage revisited. Pediatrics. 2004;114(6):e689-e693. doi:10.1542/peds.2004-1037

4. Kuo H-C, Lo M-H, Hsieh K-S, Guo M, Huang Y-H. High-dose aspirin is associated with anemia and dose not confer benefit to disease outcomes in Kawasaki disease. PLOS One. 2015. doi:10.1371/journal.pone.0144603

5. Wang H, Shimizu C, Bainto E, et al. Subgroups of children with Kawasaki disease: A data-driven cluster analysis. The Lancet Child & Adolescent. 2023;7(10):697-707. doi:10.1016/S2352-4642(23)00166-9