COMMENTARY

Kawasaki Disease: High- or Low-Dose Aspirin?

William T. Basco, Jr., MD, MS

Disclosures

September 12, 2017

High- vs Low-Dose Aspirin for Treatment of Kawasaki Disease

Given that 15%-25% of children with untreated Kawasaki disease will develop coronary artery aneurysms or dilation, intravenous immunoglobulin (IVIg) and aspirin are now considered standards of care for the management of this disorder. It is unclear, however, whether higher-dose aspirin should be given to achieve anti-inflammatory effects beyond the antithrombotic effects of lower-dose aspirin. Higher-dose aspirin may shorten the duration of fever, but it is unclear whether it reduces cardiovascular morbidity.

A study by Dallaire and colleagues[1] analyzed data from patients with Kawasaki disease admitted to one of five Canadian institutions from 2004 to 2015. Study children were aged 0 to 10 years, and those with structural heart disease were excluded. The investigators retrospectively compared the outcomes of children prescribed only low-dose aspirin with those who received high-dose aspirin as part of their treatment. Two of the study institutions typically dosed patients at 3-5 mg/kg/day (low-dose aspirin), whereas the other institutions typically dosed at 80 mg/kg/day (high-dose aspirin). All children, who were experiencing their first episode of Kawasaki disease, received treatment within the first 10 days of fever onset, and all received IVIg.

The investigators were able to recreate the visit history for all children through 12 months after being diagnosed with Kawasaki disease. The main outcome of interest was any coronary artery abnormality (eg, coronary artery diameter greater than a predetermined cut-off). The study took a noninferiority approach in that the two treatment doses would be considered noninferior if the difference in the risk for coronary artery abnormalities was ≤5%. The analysis cohort included 1213 children, 848 of whom were treated at high-dose aspirin institutions. In general, the treatment groups were not different at enrollment for age, sex, or duration of fever before treatment.

Study Findings

Overall, 21% of the children experienced a coronary artery abnormality. However, about half of those changes were considered transient because they were no longer present at the 6-week follow-up evaluation. Coronary artery abnormalities persisted at follow-up in 12.9% of the children. The frequency of any coronary abnormality was similar between the two groups (20.5% of the high-dose aspirin patients vs 22.2% of the low-dose aspirin children). The adjusted difference was 0.3%, with a 95% confidence interval of -4.5% to 5.0%. Similarly, coronary artery abnormalities persisted in 13.2% of high-dose patients compared with 12.3% of low-dose patients, a difference that did not reach statistical significance in the adjusted risk models. Additional analyses, including looking at the sizes of the coronary artery abnormalities, did not show any differences. Retreatment frequency was also similar (24.4% in the high-dose group and 27.4% in the low-dose group, a difference that was not statistically significant in adjusted models). Finally, duration of fever was 7.8 days in both groups.

The investigators concluded that with respect to coronary artery abnormalities or secondary outcomes, low-dose aspirin is not inferior to high-dose aspirin treatment of Kawasaki disease.

Viewpoint

In 20 years of practice at my institution, we have gradually shifted from using high-dose to low-dose aspirin, making me wonder what our data might show! As the study authors acknowledge, data to suggest that aspirin adds anything to treatment with IVIg are limited, and no prospective, randomized, double-blind trials have been conducted. Although this is a single study, combining data from five institutions strengthens the findings, and the investigators attempted to control for important clinical covariates, including some measures of disease severity. For now, I have to agree that despite our lack of randomized, prospective clinical trials, their data suggest that low-dose aspirin can be considered noninferior to high-dose aspirin for the treatment of Kawasaki disease in children.

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