title: FK506 effectiveness in reducing acute rejection after heart transplantation: a prospective randomized study.
abstract: BACKGROUND
  Tacrolimus (FK506) has recently become available clinically as an alternative to cyclosporine-based immunosuppression. This study reports the middle-term results of a prospective, randomized trial that compared FK506 with cyclosporine-based immunosuppression in heart transplant recipients.
  
  
  METHODS
  Twenty-five consecutive patients were randomized at a 2:1 ratio into two groups, one of which received FK506 (15 patients), the other cyclosporine (10 patients). Both groups received similar concomitant immunosuppression. The patients were followed up for 12 months. The following outcome parameters were analyzed: survival, rejection and infection rate, lymphocyte subsets, new-onset diabetes, renal and hepatic function, hypertension, right-sided heart catheterization data, graft coronary artery disease, and neurologic side effects.
  
  
  RESULTS
  The mortality rate (two patients) in the FK506 group was 13% versus 0% in the cyclosporine group (p = NS). The two deaths were the consequences of early infections and higher doses of FK506. From the outset, the FK506 group presented a lower prevalence of acute rejection, a lower requirement for rejection treatments and a higher incidence of infections. Accordingly, we reduced overall immunosuppression for the last seven patients in the FK506 group; the decrease in FK506 and prednisone dosage led to a decrease in the early infection rate without an increase in the rejection rate. There was no difference between the two groups in diabetes incidence, renal and hepatic function, right-sided heart catheterization data, or coronary angiograms. Hypertension was less frequent and milder in the FK506 group.
  
  
  CONCLUSIONS
  This experience suggests that FK506 can be safely used in heart transplantation. It can decrease the frequency of rejection episodes. Low-dose administration allows a lower infection rate without an increase in rejection. With a protocol of delayed starting and low dosing, side effects such as renal toxicity, hypertension, and neurologic toxicity seem to be unlikely. Further studies are needed to establish the exact dosage and therapeutic levels of the drug.
authors.affiliation: Department of Cardiac Surgery, Charles Dubost Center, IRCCS Policlinico S. Matteo, University of Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rinaldi
authors.forename: C
authors.initials: C
authors.lastname: Pellegrini
authors.forename: L
authors.initials: L
authors.lastname: Martinelli
authors.forename: C
authors.initials: C
authors.lastname: Goggi
authors.forename: A
authors.initials: A
authors.lastname: Gavazzi
authors.forename: C
authors.initials: C
authors.lastname: Campana
authors.forename: E
authors.initials: E
authors.lastname: Arbustini
authors.forename: P
authors.initials: P
authors.lastname: Grossi
authors.forename: M
authors.initials: M
authors.lastname: Regazzi
authors.forename: G
authors.initials: G
authors.lastname: Ippoliti
authors.forename: M
authors.initials: M
authors.lastname: Vigano
mesh_terms: D000208:Acute Disease; D001424:Bacterial Infections; D006328:Cardiac Catheterization; D003327:Coronary Disease / Q000209:etiology; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000187:drug effects; D015995:Prevalence; D011446:Prospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus