title: Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial.
abstract: BACKGROUND
  Sirolimus reduces acute rejection in renal transplant recipients and prevents vasculopathy in nonhuman primates and in-stent restenosis in humans. Its effects on rejection and transplant vasculopathy in human heart transplant recipients are unknown.
  
  
  RESULTS
  In a randomized, open-label study, sirolimus was compared with azathioprine in combination with cyclosporine and steroids administered from the time of cardiac transplantation. We report 6-month rejection rates (primary end point), 12-month safety and efficacy data, and 6- and 24-month graft vasculopathy data in 136 cardiac allograft recipients randomly assigned (2:1) to sirolimus (n=92) or azathioprine (n=44). At 6 months, the proportion of patients with grade 3a or greater acute rejection was 32.4% for sirolimus 3 mg/d (P=0.027), 32.8% for sirolimus 5 mg/d (P=0.013), and 56.8% for azathioprine. Patient survival at 12 months was comparable among groups. Intracoronary ultrasound at 6 weeks, 6 months, and 2 years demonstrated highly significant progression of transplant vasculopathy in azathioprine-treated patients. At 6 months, a highly significant absence of progression in intimal plus medial proliferation and significant protection against luminal encroachment was evident in sirolimus-treated patients, and these effects were sustained at 2 years.
  
  
  CONCLUSIONS
  Sirolimus use from the time of transplantation approximately halved the number of patients experiencing acute rejection. The measurable development of transplant vasculopathy at 6 months and 2 years in patients receiving azathioprine was not observed in patients receiving sirolimus.
authors.affiliation: St Vincent's Hospital, Xavier 4, Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. amkeogh@stvincents.com.au
authors.forename: Anne
authors.initials: A
authors.lastname: Keogh
authors.forename: Meroula
authors.initials: M
authors.lastname: Richardson
authors.forename: Peter
authors.initials: P
authors.lastname: Ruygrok
authors.forename: Phillip
authors.initials: P
authors.lastname: Spratt
authors.forename: Andrew
authors.initials: A
authors.lastname: Galbraith
authors.forename: Gerry
authors.initials: G
authors.lastname: O'Driscoll
authors.forename: Peter
authors.initials: P
authors.lastname: Macdonald
authors.forename: Don
authors.initials: D
authors.lastname: Esmore
authors.forename: David
authors.initials: D
authors.lastname: Muller
authors.forename: Steve
authors.initials: S
authors.lastname: Faddy
mesh_terms: D000208:Acute Disease; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D003324:Coronary Artery Disease / Q000517:prevention & control*; D003404:Creatinine / Q000097:blood; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007239:Infections / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D014463:Ultrasonography
chemical_list: D007166:Immunosuppressive Agents; D008055:Lipids; D003404:Creatinine; D001379:Azathioprine; D020123:Sirolimus