title: Superior rejection profile during the first 24 months after heart transplantation under tacrolimus as baseline immunosuppressive regimen.
abstract: BACKGROUND
  The use of tacrolimus (TAC) in patients after heart transplantation (HTX) has increased over the last few years.
  
  
  OBJECTIVE
  In this retrospective study, we evaluated the effects of a TAC (conventional and extended-release TAC)-based immunosuppressive therapy regarding rejection profile in comparison to a cyclosporine A (CSA)-based regimen in patients after HTX.
  
  
  METHODS
  The data of 233 patients who underwent HTX at the Heidelberg Heart Transplantation Center from May 1998 until November 2010 were retrospectively analyzed. Primary immunosuppressive therapy was changed from a CSA (n=114) to a TAC (n=119)-based regimen in February 2006 according to center routine. Follow-up period was 2 years post-HTX. Primary endpoint was time to first biopsy-proven rejection requiring therapy. In all patients, routine follow-up at the Heidelberg Heart Transplantation Center was mandatory.
  
  
  RESULTS
  Multivariate risk factor analysis regarding time to first rejection episode showed no statistically significant differences regarding recipient age, donor age, recipient sex, donor sex, sex mismatch, ischemic time, and diagnosis leading to HTX between the two groups (all P= not statistically significant). Time to first biopsy-proven rejection was significantly longer in the TAC group (intention-to-treat analysis, n=233, log-rank test P<0.0001; per-protocol analysis, n=150, log-rank test P=0.0003). In patients who underwent a change of primary immunosuppression (n=49), a significantly longer time to first biopsy-proven rejection was also found in the primary TAC subgroup (log-rank test P=0.0297). Further subgroup analysis in the TAC subgroups showed no statistically significant differences in time to biopsy-proven rejection under extended-release TAC compared to conventional TAC (intention-to-treat analysis, log-rank test P=0.1736).
  
  
  CONCLUSIONS
  Our study demonstrated that a TAC-based primary immunosuppressive therapy is superior to a CSA-based immunosuppressive regimen in patients after HTX regarding time to first biopsy-proven rejection.
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Helmschrott
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Beckendorf
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Ceylan
authors.initials: C
authors.lastname: Akyol
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Arjang
authors.initials: A
authors.lastname: Ruhparwar
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schmack
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Erbel
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Gleissner
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Akhavanpoor
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ehlermann
authors.affiliation: Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Department of Cardiology, Angiology, Pneumology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Andreas O
authors.initials: AO
authors.lastname: Doesch
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D016572:Cyclosporine / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D016559:Tacrolimus
keywords: cyclosporine A; extended-release tacrolimus; renal function