Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial.
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.
Keogh
Anne
A
St Vincent's Hospital, Xavier 4, Victoria St, Darlinghurst, Sydney, New South Wales 2010, Australia. amkeogh@stvincents.com.au
Richardson
Meroula
M
Ruygrok
Peter
P
Spratt
Phillip
P
Galbraith
Andrew
A
O'Driscoll
Gerry
G
Macdonald
Peter
P
Esmore
Don
D
Muller
David
D
Faddy
Steve
S
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
D007166:Immunosuppressive Agents; D008055:Lipids; D003404:Creatinine; D001379:Azathioprine; D020123:Sirolimus