title: Prevention of acute rejection and allograft vasculopathy by everolimus in cardiac transplants recipients: a 24-month analysis.
abstract: BACKGROUND
  Everolimus is an immunosuppressive agent that reduces cardiac allograft vasculopathy. This report presents the 24-month results of a multicenter trial of everolimus vs azathioprine in heart transplantation.
  
  
  METHODS
  A total of 634 patients were randomized to receive 1.5 mg everolimus, 3 mg everolimus or azathioprine, with cyclosporine and steroids. A 12-month, double-blind, double-dummy period was followed by a 12-month open-label period.
  
  
  RESULTS
  At 24 months, the percentage of patients reaching the composite efficacy end-points was significantly lower with everolimus (1.5 mg: 45.9%, p = 0.016; 3 mg: 36.0%, p < 0.001) than with azathioprine (57.5%). The change in maximal intimal thickness from baseline to 24 months was significantly smaller with everolimus 1.5 mg (0.07 mm, p = 0.014) and 3 mg (0.06 mm, p = 0.004) compared with azathioprine (0.15 mm). The 24-month incidence of vasculopathy was 33.3% with everolimus 1.5 mg, 45.5% with everolimus 3 mg and 58.3% with azathioprine (p = 0.017 vs everolimus 1.5 mg). Incidence of cytomegalovirus infection was 3-fold lower in patients receiving everolimus compared with azathioprine (7.2% and 7.1% in the 1.5-mg and 3-mg everolimus cohorts, respectively, and 21% in the azathioprine group; p < 0.0001). Median serum creatinine levels at 24 months were higher with everolimus than with azathioprine, but decreased when cyclosporine exposure was reduced (everolimus 1.5 mg: baseline 167 micromol, after 6 months 157.5 micromol; everolimus 3 mg: baseline 185.6 micromol, after 6 months 160 micromol; azathioprine: baseline 123.3 micromol, after 6 months 127 micromol).
  
  
  CONCLUSIONS
  Everolimus significantly reduced acute rejection and limited the progression of allograft vasculopathy at 24 months compared with azathioprine. Although graft and patient survival was comparable at 24 months, everolimus therapy may improve longer-term outcomes after heart transplantation.
authors.affiliation: Department of Cardiac Surgery, San Matteo Hospital, Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Viganò
authors.forename: Murat
authors.initials: M
authors.lastname: Tuzcu
authors.forename: Raymond
authors.initials: R
authors.lastname: Benza
authors.forename: Pascale
authors.initials: P
authors.lastname: Boissonnat
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: James
authors.initials: J
authors.lastname: Hill
authors.forename: Guenther
authors.initials: G
authors.lastname: Laufer
authors.forename: Robert
authors.initials: R
authors.lastname: Love
authors.forename: Jayan
authors.initials: J
authors.lastname: Parameshwar
authors.forename: Luis Alonso
authors.initials: LA
authors.lastname: Pulpón
authors.forename: Dale
authors.initials: D
authors.lastname: Renlund
authors.forename: Kamal
authors.initials: K
authors.lastname: Abeywickrama
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cretin
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Eisen
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004311:Double-Blind Method; D000068338:Everolimus; D006084:Graft Rejection / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008875:Middle Aged; D012449:Safety; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014184:Transplantation, Homologous / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D001379:Azathioprine; D020123:Sirolimus