Everolimus Versus Mycophenolate Mofetil in Heart Transplantation: A Randomized,Multicenter Trial |
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| Authors: | H J Eisen J Kobashigawa R C Starling D F Pauly A Kfoury H Ross S‐S Wang B Cantin A Van Bakel G Ewald S Hirt H Lehmkuhl A Keogh M Rinaldi L Potena A Zuckermann G Dong C Cornu‐Artis P Lopez |
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| Institution: | 1. Division of Cardiology, Drexel University College of Medicine, Hahnemann University Hospital, , Philadelphia, PA;2. Cedars‐Sinai Heart Institute, , Los Angeles, CA;3. Kaufman Center for Heart Failure, Heart and Vascular Institute, Cleveland Clinic Foundation, , Cleveland, OH;4. Division of Cardiovascular Medicine, University of Florida College of Medicine, , Gainesville, FL;5. Intermountain Medical Center, , Salt Lake City, UT;6. Department of Cardiology/Heart Transplant, University Health Network, Toronto General Hospital, , Toronto, Ontario, Canada;7. Division of Cardiovascular Surgery, National Taiwan University, , Taipei, Taiwan;8. Quebec Heart Institute, , Quebec, Quebec, Canada;9. Medical University of South Carolina, , Charleston, SC;10. Washington University School of Medicine, , St. Louis, MO;11. University Hospital Regensburg, , Regensburg, Germany;12. German Heart Center Berlin, , Berlin, Germany;13. Heart and Lung Transplant Unit, St. Vincents Hospital, , Darlinghurst, Sydney, Australia;14. Az.Ospedaliero‐Universitaria, S.Giovanni Battista di Torino, , Torino, Italy;15. School of Medicine, University of Bologna, , Bologna, Italy;16. Department of Cardiothoracic Surgery, University of Vienna, , Vienna, Austria;17. Novartis Pharmaceuticals, , East Hanover, NJ;18. Novartis Pharma AG, , Basel, Switzerland |
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| Abstract: | In an open‐label, 24‐month trial, 721 de novo heart transplant recipients were randomized to everolimus 1.5 mg or 3.0 mg with reduced‐dose cyclosporine, or mycophenolate mofetil (MMF) 3 g/day with standard‐dose cyclosporine (plus corticosteroids ± induction). Primary efficacy endpoint was the 12‐month composite incidence of biopsy‐proven acute rejection, acute rejection associated with hemodynamic compromise, graft loss/retransplant, death or loss to follow‐up. Everolimus 1.5 mg was noninferior to MMF for this endpoint at month 12 (35.1% vs. 33.6%; difference 1.5% 97.5% CI: –7.5%, 10.6%]) and month 24. Mortality to month 3 was higher with everolimus 1.5 mg versus MMF in patients receiving rabbit antithymocyte globulin (rATG) induction, mainly due to infection, but 24‐month mortality was similar (everolimus 1.5 mg 10.6% 30/282], MMF 9.2% 25/271]). Everolimus 3.0 mg was terminated prematurely due to higher mortality. The mean (SD) 12‐month increase in maximal intimal thickness was 0.03 (0.05) mm with everolimus 1.5 mg versus 0.07 (0.11) mm with MMF (p < 0.001). Everolimus 1.5 mg was inferior to MMF for renal function but comparable in patients achieving predefined reduced cyclosporine trough concentrations. Nonfatal serious adverse events were more frequent with everolimus 1.5 mg versus MMF. Everolimus 1.5 mg with reduced‐dose cyclosporine offers similar efficacy to MMF with standard‐dose cyclosporine and reduces intimal proliferation at 12 months in de novo heart transplant recipients. |
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| Keywords: | Cardiac allograft vasculopathy cyclosporine everolimus heart transplantation mycophenolate mofetil randomized |
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