Prevalence of coronary artery abnormalities in Kawasaki disease is highly dependent on gamma globulin dose but independent of salicylate dose

Abstract

The efficacy of intravenous gamma globulin (IVGG) for treatment of Kawasaki disease (KD) is clearly established. In a metaanalysis, we reviewed U.S. and Japanese multicenter, randomized controlled studies regarding the effect of various doses of IVGG with aspirin administered within the first 7 to 10 days of illness on the prevalence of coronary artery abnormalities in KD. We studied 1629 patients with acute KD from the six reported studies that included blinded echocardiographic assessments. In 868 Japanese patients treated with moderate-dose aspirin (30 to 50 mg/kg per day), the prevalence of coronary abnormalities at the subacute stage (illness day 30) was 26.8% with aspirin alone, 18.1% with total IVGG dose < 1 gm/kg, 17.3% with total IVGG of 1.0 to 1.2 g/kg, and 5.3% with total IVGG of 2 gm/kg; the corresponding prevalence at the convalescent stage of illness (illness day 60) was 17.5%, 13.5%, 9.8%, and 3.5%, respectively. In 761 U.S. patients treated with high-dose aspirin (80 to 120 mg/kg per day), the prevalence of coronary abnormalities at the subacute stage (2 to 3 weeks after enrollment) was 23.0% with aspirin alone, 9.0% with total IVGG of 1.0 gm/kg, 8.6% with total IVGG of 1.6 gm/kg, and 4.6% with total IVGG of 2.0 gm/kg; corresponding prevalence at the convalescent stage (6 to 8 weeks after enrollment) was 17.7%, 9.0%, 6.3%, and 3.8%, respectively. When all data for the 1629 patients were combined, the prevalence at the subacute stage was 25.8% with aspirin alone, 18.1% with IVGG < 1 gm/kg, 15.7% with IVGG of 1 to 1.2 gm/kg, 8.6% with IVGG of 1.6 gm/kg, and 4.8% with IVGG of 2 gm/kg (adjusted R2 = 0.966, p = 0.0017); corresponding prevalence at the convalescent stage was 17.6%, 13.5%, 9.7%, 6.3%, and 3.8%, respectively (adjusted R2 = 0.993, p = 0.0602). The prevalence of coronary abnormalities was inversely related to the total dose of IVGG and was independent of the aspirin dose. We conclude that 2 gm/kg IVGG combined with at least 30 to 50 mg/kg per day aspirin provides maximum protection against development of coronary abnormalities after KD.