title: Ten-year results of a randomized trial comparing tacrolimus versus cyclosporine a in combination with mycophenolate mofetil after heart transplantation.
abstract: BACKGROUND
  Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after heart transplantation (HTX) are rarely published. Therefore, we collected long-term follow-up data of an intervention cohort 10 years after randomization.
  
  
  METHODS
  Ten-year follow-up data of 60 patients included in a prospective, randomized trial between 1998 and 2000 were analyzed as intention-to-treat (TAC-MMF n=30; CsA-MMF n=30). Baseline characteristics were well balanced. Cardiac allograft vasculopathy (CAV) was graduated in accordance with the new ISHLT classification.
  
  
  RESULTS
  Survival at 1, 5, and 10 years was 96.7%, 80.0%, and 66.7% for TAC-MMF and 90.0%, 83.3%, and 80.0% for CsA-MMF (P=ns). Freedom from acute rejection (AR) was significantly higher in TAC-MMF versus CsA-MMF (65.5% vs. 21.7%, log-rank 8.3, P=0.004). Freedom from ISHLT≥CAV1 after 5 and 10 years was in TAC-MMF 64.0% and 45.8%, and in CsA-MMF 36.0% (log-rank 3.0, P=0.085) and 8.0% (log-rank 9.0, P=0.003). No difference in long-term results for freedom from coronary angioplasty or stenting, renal dysfunction, diabetes mellitus, CMV infection, or malignancy was detected.
  
  
  CONCLUSIONS
  Cross-over effects because of treatment switch may result in impairment of significance between the groups. The long-term analysis resulted in a significant difference in manifestation of CAV between the groups after 10 years. Less rejection in the TAC-group might have contributed to the lower incidence of CAV. Superior freedom from AR and CAV in the TAC-MMF group did not result in better long-term survival.
authors: DepDepartment of Cardiac Surgery, University of Munich, Marchioninistr. 15, 81377 München, Germany. Sonja.Guethoff@med.uni-muenchen.de
authors: Sonja
authors: S
authors: Guethoff
authors: Bruno M
authors: BM
authors: Meiser
authors: Jan
authors: J
authors: Groetzner
authors: Sandra
authors: S
authors: Eifert
authors: Carola
authors: C
authors: Grinninger
authors: Peter
authors: P
authors: Ueberfuhr
authors: Bruno
authors: B
authors: Reichart
authors: Christian
authors: C
authors: Hagl
authors: Ingo
authors: I
authors: Kaczmarek
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D003324:Coronary Artery Disease / Q000209:etiology / Q000628:therapy; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D011446:Prospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus