title: Increased incidence of acute graft rejection on calcineurin inhibitor-free immunosuppression after heart transplantation.
abstract: BACKGROUND
  Calcineurin inhibitor (CNI)-free immunosuppression is used increasingly after heart transplantation to avoid CNI toxicity, but in the absence of a randomized trial, concerns remain over an increased rejection risk.
  
  
  METHODS
  We studied the incidence of graft rejection episodes among all cardiac graft recipients, beginning with the first introduction of CNI-free protocols. We compared events during CNI-free and CNI-containing immunosuppression among 231 transplant recipients of overall mean age 55.2 ± 11.8 years, from a mean 5.2 ± 5.4 years after transplantation through a mean follow-up of 3.1 ± 1.4 years. We considered as acute rejection episodes requiring treatment those of International Society for Heart and Lung Transplantation.
  
  
  RESULTS
  During the total follow-up of 685 patient years (CNI-containing, 563; CNI-free, 122), we performed 1,374 biopsies which diagnosed 78 rejection episodes. More biopsies were performed in CNI-free patients: biopsies/patient-month of CNI-containing, 0.13 versus CNI-free, 0.22 (P < .05). The incidence of rejection episodes per patient-month was significantly higher on CNI-free compared with CNI therapy, among patients switched both early and later after heart transplantation, namely, within 1 year, 0.119 versus 0.035 (P = .02); beyond 1 year, 0.011 versus 0.004 (P = .007); beyond 2 years, 0.007 versus 0.003 (P = .04); and beyond 5 years: 0.00578 versus 0.00173 (P = .04).
  
  
  CONCLUSIONS
  Rejection incidence during CNI-free immunosuppression protocols after heart transplantation was significantly increased in both early and later postoperative periods. Given the potentially long delay to rejection occurrence, patients should be monitored closely for several months after a switch to CNI-free immunosuppressive protocols.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. sultan.celik@med.uniheidelberg.de
authors.forename: S
authors.initials: S
authors.lastname: Celik
authors.forename: A O
authors.initials: AO
authors.lastname: Doesch
authors.forename: M H
authors.initials: MH
authors.lastname: Konstandin
authors.forename: A V
authors.initials: AV
authors.lastname: Kristen
authors.forename: K
authors.initials: K
authors.lastname: Ammon
authors.forename: F-U
authors.initials: FU
authors.lastname: Sack
authors.forename: P
authors.initials: P
authors.lastname: Schnabel
authors.forename: H A
authors.initials: HA
authors.lastname: Katus
authors.forename: T J
authors.initials: TJ
authors.lastname: Dengler
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D002423:Cause of Death; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents