Abstract
Aspirin has been used as a concomitant drug in the treatment of Kawasaki disease (KD). In recent years, there has been discussion concerning whether high-dose aspirin is appropriate for treatment in the acute phase of KD. We retrospectively investigated the incidence of coronary artery abnormalities (CAAs) and the antipyretic effect of 30 to 50 mg/kg/day aspirin, the minimum and the maximum approved doses in Japan. This was a single-center, non-randomized, retrospective, historical cohort study. Patients were routinely treated with 50 mg/kg/day aspirin (50-mg Group) between 2007 and April 2014, and with 30 mg/kg/day aspirin (30-mg Group) between May 2014 and 2016. All patients were given initial and, if necessary, subsequent intravenous immunoglobulin (IVIG) 2.0 g/kg. The primary endpoint was incidence of CAAs defined as a CA diameter with a Z score ≥2.5 at treatment week 4. The secondary endpoint was incidence of further treatment. Incidences were compared using inverse probability weighting analysis adjusting for age, sex, and risk scores. In 587 patients, there was no significant difference in incidence of CAAs (odds ratio in 30-mg Group 0.769, 95% confidence interval (CI): 0.537–1.101, p = 0.151). Risk of further treatment after the first IVIG in the 30-mg Group was significantly higher than that in the 50-mg Group (odds ratio 1.379, 95% CI: 1.051–1.811, p = 0.021). Although this study has some limitations, the findings suggest that aspirin 50 mg/kg/day may have no significant effect on improving incidence of CAAs compared with 30 mg/kg/day but may have a lower rate of further treatment.
Highlights
Kawasaki disease (KD), which is an acute vasculitis in young children and causes coronary artery abnormalities (CAAs) such as coronary artery aneurysm and dilation, is the leading cause of acquired heart disease in children in developed countries [1, 2]
Exclusion criteria were as follows: patients for whom a final diagnosis of KD was clearly ruled out; patients who had preexisting CAAs before treatment diagnosed at bedside according to the Japanese Ministry of Health, Labour and Welfare criteria [15], which are based on absolute values (≥3 mm in children
68 were excluded for the following reasons: 8 patients had CAAs before treatment; 39 patients had received any treatment for KD at other hospitals before referral to our institution; and 21 patients were enrolled in a clinical study and received cyclosporine with IVIG plus acetylsalicylic acid (ASA) as first-line therapy
Summary
Kawasaki disease (KD), which is an acute vasculitis in young children and causes coronary artery abnormalities (CAAs) such as coronary artery aneurysm and dilation, is the leading cause of acquired heart disease in children in developed countries [1, 2]. In the five decades since the initial recognition of KD, the standard treatment is a combination of intravenous immunoglobulin (IVIG) and acetylsalicylic acid (ASA) [3]. High-dose (80–100 mg/kg) and medium-dose (30–50 mg/kg) ASA have been recommended as standard treatment during the acute febrile phase by the American Heart Association (AHA) and Japanese Society of Pediatric Cardiology and Cardiac Surgery (JSPCCS) [4, 5]. That prospective study compared ASA, flurbiprofen, and prednisolone plus dipyridamole [6]. A US study prior to the spread of immunoglobulin therapy has shown that ASA suppresses the development of CAAs [8]
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