title: Tacrolimus with mycophenolate mofetil or sirolimus compared with calcineurin inhibitor-free immunosuppression (sirolimus/mycophenolate mofetil) after heart transplantation: 5-year results.
abstract: BACKGROUND
  Despite improvements in immunosuppressive therapy, the most advantageous combination for cardiac transplant recipients has not been established. This randomized controlled trial was performed to evaluate the efficacy and safety of 3 immunosuppressive protocols.
  
  
  METHODS
  Between 2003 and 2005, 78 de novo cardiac transplant recipients were randomized 2:2:1 to receive steroids and tacrolimus plus mycophenolate mofetil (TAC/MMF; n = 34), TAC and sirolimus (TAC/SRL; n = 29), or SRL and MMF (SRL/MMF) plus anti-thymocyte globulin (ATG; n = 15). Steroids were withdrawn after 6 months.
  
  
  RESULTS
  The 5-year survival was 85.3% for TAC/MMF, 93.1% for TAC/SRL, and 86.7% for SRL/MMF (p = 0.31 for TAC/MMF vs TAC/SIR; p = 0.47 for TAC/MMF vs SIR/MMF and p = 0.86 for TAC/SIR vs SIR/MMF). Despite the use of ATG, patients in the SRL/MMF group revealed numerically fewer freedom from acute rejection episodes: TAC/MMF, 82.4%; TAC/SRL, 85.2%; SRL/MMF, 73.3% (p = 0.33). Mean creatinine at 5 years revealed preservation of renal function in the SRL/MMF vs the TAC/MMF group (p = 0.045): TAC/MMF, 1.70±0.91 mg/dl; TAC/SRL, 1.44±0.65 mg/dl; and SRL/MMF, 1.25±0.46 mg/dl. Freedom from cardiac allograft vasculopathy was improved in the SRL/MMF group (93.3%) compared with TAC/MMF (73.5%) and TAC/SRL (80.8%) groups, reaching no statistical significance. Freedom from cytomegalovirus infection was TAC/MMF, 72.2%; TAC/SRL, 89.7%; and SRL/MMF, 86.7%. There was a trend toward improved freedom from cytomegalovirus infection with TAC/SRL vs TAC/MMF (p = 0.076). More frequent discontinuations of study medication occurred in SRL-based immunosuppression protocols (TAC/SRL vs TAC/MMF, p = 0.034; SRL/MMF vs TAC/MMF, p = 0.003).
  
  
  CONCLUSIONS
  The 3 strategies yield no survival advantage at 5 years, with higher numeric rates of rejection and adverse effects in the calcineurin inhibitor-free arm. A trend was observed in favor of freedom from cardiac allograft vasculopathy and preservation of renal function in the calcineurin inhibitor-free arm. However, the clinical relevance on outcomes is unclear because only few patients were receiving the assigned treatment protocols.
authors: Transplantation Center Munich, Ludwig-Maximilians-University, Munich, Germany. ingo.kaczmarek@med.uni-muenchen.de
authors: Ingo
authors: I
authors: Kaczmarek
authors: Marc-Michael
authors: MM
authors: Zaruba
authors: Andres
authors: A
authors: Beiras-Fernandez
authors: Ricarda
authors: R
authors: Reimann
authors: Thomas
authors: T
authors: Nickel
authors: Carola
authors: C
authors: Grinninger
authors: Sebastian
authors: S
authors: Sadoni
authors: Christian
authors: C
authors: Hagl
authors: Bruno
authors: B
authors: Meiser
mesh_terms: D004359:Drug Therapy, Combination; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; 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; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus