Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm

Research output: Contribution to journalArticle


  • Adriana H. Tremoulet
  • Sonia Jain
  • Pei Ni Jone
  • Brookie M. Best
  • Elizabeth H. Duxbury
  • Alessandra Franco
  • Beth Printz
  • Samuel R. Dominguez
  • Heather Heizer
  • Marsha S. Anderson
  • Mary P. Glodé
  • Feng He
  • Robert L. Padilla
  • Chisato Shimizu
  • Emelia Bainto
  • Joan Pancheri
  • Harvey J. Cohen
  • John C. Whitin
  • Jane C. Burns

External Institution(s)

  • University of California at San Diego
  • Rady Children's Hospital
  • Department of Family Medicine and Public Health
  • Skaggs School of Pharmacy & Pharmaceutical Sciences
  • University of Colorado Denver
  • Stanford University


Original languageEnglish (US)
Pages (from-to)107-117.e12
JournalJournal of Pediatrics
StatusPublished - Dec 2019


Objectives: To determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of a 6-week course of atorvastatin in patients with acute Kawasaki disease with coronary artery (CA) aneurysm (CAA). Study design: This was a Phase I/IIa 2-center dose-escalation study of atorvastatin (0.125-0.75 mg/kg/day) in 34 patients with Kawasaki disease (aged 2-17 years) with echocardiographic evidence of CAA. We measured levels of the brain metabolite 24(S)-hydroxycholesterol (24-OHC), serum lipids, acute-phase reactants, liver enzymes, and creatine phosphokinase; peripheral blood mononuclear cell populations; and CA internal diameter normalized for body surface area before atorvastatin treatment and at 2 and 6 weeks after initiation of atorvastatin treatment. Results: A 6-week course of up to 0.75 mg/kg/day of atorvastatin was well tolerated by the 34 subjects (median age, 5.3 years; IQR, 2.6-6.4 years), with no serious adverse events attributable to the study drug. The areas under the curve for atorvastatin and its metabolite were larger in the study subjects compared with those reported in adults, suggesting a slower rate of metabolism in children. The 24-OHC levels were similar between the atorvastatin-treated subjects and matched controls. Conclusions: Atorvastatin was safe and well tolerated in our cohort of children with acute Kawasaki disease and CAA. A Phase III efficacy trial is warranted in this patient population, which may benefit from the known anti-inflammatory and immunomodulatory effects of this drug.

    Research areas

  • Kawasaki disease, atorvastatin, coronary artery abnormalities, statin

Citation formats


Tremoulet, A. H., Jain, S., Jone, P. N., Best, B. M., Duxbury, E. H., Franco, A., ... Burns, J. C. (2019). Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm. Journal of Pediatrics, 215, 107-117.e12.


Tremoulet, AH, Jain, S, Jone, PN, Best, BM, Duxbury, EH, Franco, A, Printz, B, Dominguez, SR, Heizer, H, Anderson, MS, Glodé, MP, He, F, Padilla, RL, Shimizu, C, Bainto, E, Pancheri, J, Cohen, HJ, Whitin, JC & Burns, JC 2019, 'Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm', Journal of Pediatrics, vol. 215, pp. 107-117.e12.