Effect of initial corticosteroid therapy on coronary artery aneurysm formation in Kawasaki disease: a meta-analysis of 862 children

Angela C Wooditch, Stephen C Aronoff
Pediatrics 2005, 116 (4): 989-95

OBJECTIVE: Kawasaki disease is an acute vasculitis of infancy and childhood. When untreated, 15% to 25% of patients develop coronary artery aneurysms. Although the use of aspirin and intravenous immune globulin (IVIG) as initial therapy is well established, the role of corticosteroids is uncertain. The objective of this study was to identify clinical trials that compared the rate of coronary aneurysm formation after initial therapy with corticosteroids or an appropriate control and to determine the overall efficacy of corticosteroid therapy for the initial treatment of Kawasaki disease.

METHODS: Published studies were identified by searches of the Medline and the Cochrane Central Register of Controlled Trials databases as well as hand searches of selected references. Studies were included when (1) all subjects had a stated diagnosis of Kawasaki disease; (2) a corticosteroid preparation was included as part of the initial management of the disease process; (3) a therapeutically matched control group was included for the entire study, or subsets of patients that received a therapeutic intervention identical to the experimental group except for the inclusion of a corticosteroid compound could be identified; and (4) 2-dimensional echocardiography or coronary artery catheterization was performed at least 2 weeks after therapy to detect the presence of coronary aneurysms. Included studies were evaluated for quality and heterogeneity. Meta-analysis was performed using a fixed-effects model.

RESULTS: Eight studies fulfilled criteria for inclusion. Because 2 of these studies provided adequate detail to permit evaluation of 2 subgroups each, a total of 10 groups were available for evaluation. The significant heterogeneity that existed among the 10 studies (Q = 21.9, I2 = 59.0) was eliminated when 2 studies with markedly different study designs were removed (Q = 5.59, I2 = 0.00). Meta-analysis of the remaining 8 studies revealed a significant reduction in the incidence of coronary artery aneurysms among patients who received corticosteroid therapy plus aspirin +/- IVIG compared with aspirin +/- IVIG alone (odds ratio [OR] 0.546; 95% confidence interval [CI]: 0.371-0.803); the benefit of corticosteroid therapy was maintained when study subsets of aspirin alone (OR: 0.601; 95% CI: 0.392-0.921) or aspirin + IVIG (OR: 0.352; 95% CI: 0.136-0.909) were compared with matched regimens that contained corticosteroids.

CONCLUSION: The inclusion of corticosteroids in aspirin-containing regimens for the initial treatment of Kawasaki disease reduces the incidence of coronary aneurysms.

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