Published online before print July 19, 2004, doi: 10.1161/01.CIR.0000136812.90177.94
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(Circulation. 2004;110:2694-2700.)
© 2004 American Heart Association, Inc.
Transplantation |
Sirolimus in De Novo Heart Transplant Recipients Reduces Acute Rejection and Prevents Coronary Artery Disease at 2 Years
A Randomized Clinical Trial
From St Vincent’s Hospital, Sydney, New South Wales (A.K., P.S., P.M., D.M., S.F.); Alfred Hospital, Melbourne, Victoria (M.R., D.E.); Prince Charles Hospital, Brisbane, Queensland (A.G.); and Royal Perth Hospital, Perth, Western Australia (G.O.), Australia, and Green Lane Hospital, Auckland, New Zealand (P.R.).
Correspondence to Associate Professor Anne Keogh, St Vincent’s Hospital, Xavier 4, Victoria St, Darlinghurst, Sydney, NSW 2010, Australia. E-mail amkeogh{at}stvincents.com.au
Received March 7, 2004; revision received June 3, 2004; accepted June 3, 2004.
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.
Methods and 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.
Key Words: sirolimus • rejection • cardiac transplant vasculopathy
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