A Phase I/IIa Dose Escalating, Open-label Study of Atorvastatin in Children with Acute Kawasaki Disease and Coronary Artery Abnormalities

Background: Although high-dose intravenous immunoglobulin plus aspirin reduces the risk of coronary artery damage, 5-10% of children with Kawasaki disease (KD) will go on to develop coronary artery aneurysms that may result in myocardial ischemia, infarction, or death. Arterial damage in KD results from immune activation and vessel wall infiltration by myofibroblasts, neutrophils, and T-cells with secretion of pro-inflammatory cytokines, elastases, and matrix metalloproteinases. Resolution of inflammation and recovery from the acute illness occurs through T-cell regulation. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, have extensive anti-inflammatory effects that target all of these pathways. These effects are independent of their cholesterol-lowering effect. Given these anti-inflammatory effects, statins would be a reasonable therapy to block coronary artery abnormality (CAA) progression in KD Methods: We designed a Phase I/IIa, two-center, dose-escalat...