title: Everolimus with reduced cyclosporine versus MMF with standard cyclosporine in de novo heart transplant recipients.
abstract: BACKGROUND
  Pharmacokinetic modeling supports trough monitoring of everolimus, but prospective data comparing this approach versus mycophenolate mofetil (MMF) in de novo cardiac transplant recipients are currently unavailable.
  
  
  METHODS
  In a 12-month multicenter open-label study, cardiac transplant patients received everolimus (trough level 3-8 ng/mL) with reduced cyclosporine A (CsA) or MMF (3 g/day) with standard CsA, both with corticosteroids+/-induction therapy.
  
  
  RESULTS
  In total, 176 patients were randomized (everolimus 92, MMF 84). Mean creatinine clearance was 72.5+/-27.9 and 76.8+/-32.1 mL/min at baseline, 65.4+/-24.7 and 72.2+/-26.2 mL/min at month 6, and 68.7+/-27.7 and 71.8+/-29.8 mL/min at month 12 with everolimus and MMF, respectively. The primary endpoint was not met since calculated CrCl at month 6 posttransplant was 6.9 mL/min lower with everolimus, exceeding the predefined margin of 6 mL/min. However, by month 12 the between-group difference had narrowed versus baseline (3.1 mL/min). All efficacy endpoints were noninferior for everolimus versus MMF. The 12-month incidence of biopsy-proven acute rejection International Heart and Lung Transplantation grade more than or equal to 3A was 21 of 92 (22.8%) with everolimus and 25 of 84 (29.8%) with MMF. Adverse events were consistent with class effects including less-frequent cytomegalovirus infection with everolimus (4 [4.4%]) than MMF (14 [16.9%], P=0.01).
  
  
  CONCLUSIONS
  Concentration-controlled everolimus with reduced CsA results in similar renal function and equivalent efficacy compared with MMF with standard CsA at 12 months after cardiac transplantation.
authors: Deutsches Herzzentrum Berlin, Berlin, Germany. lehmkuhl@dhzb.de
authors: Hans B
authors: HB
authors: Lehmkuhl
authors: José
authors: J
authors: Arizon
authors: Mario
authors: M
authors: Viganò
authors: Luis
authors: L
authors: Almenar
authors: Gino
authors: G
authors: Gerosa
authors: Massimo
authors: M
authors: Maccherini
authors: Shaida
authors: S
authors: Varnous
authors: Francesco
authors: F
authors: Musumeci
authors: J Mark
authors: JM
authors: Hexham
authors: Kevin C
authors: KC
authors: Mange
authors: Ugolino
authors: U
authors: Livi
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005060:Europe; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus