title: Statin therapy is not associated with improved outcomes after heart transplantation in children and adolescents.
abstract: BACKGROUND
  Although used routinely, the pleiotropic benefits of statins remain understudied in children after heart transplantation. We hypothesized that statin therapy would reduce the incidence of rejection, cardiac allograft vasculopathy (CAV) and post-transplant lymphoproliferative disease (PTLD).
  
  
  METHODS
  This study was a retrospective review of 964 pediatric (ages 5 to 18 years) heart transplant recipients in the multicenter Pediatric Heart Transplant Study registry from 2001 to 2012. Patients were excluded if they were undergoing re-transplantation, survived <1 year post-transplant, or had missing data regarding statin use. The effects of statins beyond the first year were estimated by Kaplan-Meier and Cox regression multivariable analysis for freedom from PTLD, rejection requiring treatment, any severity of CAV, and survival.
  
  
  RESULTS
  Statin use was variable among participating centers with only 30% to 35% of patients ≥10 years of age started on a statin at <1 year post-transplant. After the first year post-transplant, statin-treated children (average age at transplant 13.24 ± 3.29 years) had significantly earlier rejection (HR 1.42, 95% CI 1.11 to 1.82, p = 0.006) compared with untreated children (transplanted at 12 ± 3.64 years) after adjusting for conventional risk factors for rejection. Freedom from PTLD, CAV and overall survival up to 5 years post-transplant were not affected by statin use, although the number of events was small.
  
  
  CONCLUSIONS
  Statin therapy did not confer a survival benefit and was not associated with delayed onset of PTLD or CAV. Early (<1 year post-transplant) statin therapy was associated with increased later frequency of rejection. These findings suggest that a prospective trial evaluating statin therapy in pediatric heart transplant recipients is warranted.
authors.affiliation: Department of Cardiac Sciences, University of Alberta, Edmonton, Alberta, Canada. Electronic address: steven.greenway@albertahealthservices.ca.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Greenway
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Ryan
authors.initials: R
authors.lastname: Butts
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: David C
authors.initials: DC
authors.lastname: Naftel
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pruitt
authors.affiliation: Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: James K
authors.initials: JK
authors.lastname: Kirklin
authors.affiliation: Department of Cardiac Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Larsen
authors.affiliation: Department of Cardiac Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Urschel
authors.affiliation: Cardiology Section, Arkansas Children's Hospital, Little Rock, Arkansas.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Knecht
authors.affiliation: Division of Pediatric Cardiology, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Yuk
authors.initials: Y
authors.lastname: Law
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: HMG-CoA reductase inhibitors; PTLD; pediatric heart transplantation; rejection; statin; vasculopathy