Everolimus versus mycophenolate mofetil in heart transplantation: A randomized, multicenter trial

Howard 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

Research output: Contribution to journalArticle

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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. In this study comparing cardiac transplant recipients receiving one of two doses of everolimus with reduced dose cyclosporine to patients receiving mycophenolate mofetil with standard dose cyclosporine, the authors find no effect on acute cellular rejection, modestly reduced renal function, and a reduction in the incidence and severity of lesions defined by intravascular ultrasound. See editorial by Mehra on page 1119.

Original languageEnglish (US)
Pages (from-to)1203-1216
Number of pages14
JournalAmerican Journal of Transplantation
Volume13
Issue number5
DOIs
StatePublished - May 1 2013

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Mycophenolic Acid
Heart Transplantation
Multicenter Studies
Cyclosporine
Tunica Intima
Mortality
Everolimus
Kidney
Antilymphocyte Serum
Incidence
Adrenal Cortex Hormones
Hemodynamics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Eisen, H., Kobashigawa, J., Starling, R. C., Pauly, D. F., Kfoury, A., Ross, H., ... Lopez, P. (2013). Everolimus versus mycophenolate mofetil in heart transplantation: A randomized, multicenter trial. American Journal of Transplantation, 13(5), 1203-1216. https://doi.org/10.1111/ajt.12181
Eisen, Howard ; Kobashigawa, J. ; Starling, R. C. ; Pauly, D. F. ; Kfoury, A. ; Ross, H. ; Wang, S. S. ; Cantin, B. ; Van Bakel, A. ; Ewald, G. ; Hirt, S. ; Lehmkuhl, H. ; Keogh, A. ; Rinaldi, M. ; Potena, L. ; Zuckermann, A. ; Dong, G. ; Cornu-Artis, C. ; Lopez, P. / Everolimus versus mycophenolate mofetil in heart transplantation : A randomized, multicenter trial. In: American Journal of Transplantation. 2013 ; Vol. 13, No. 5. pp. 1203-1216.
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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. In this study comparing cardiac transplant recipients receiving one of two doses of everolimus with reduced dose cyclosporine to patients receiving mycophenolate mofetil with standard dose cyclosporine, the authors find no effect on acute cellular rejection, modestly reduced renal function, and a reduction in the incidence and severity of lesions defined by intravascular ultrasound. See editorial by Mehra on page 1119.",
author = "Howard Eisen and J. Kobashigawa and Starling, {R. C.} and Pauly, {D. F.} and A. Kfoury and H. Ross and Wang, {S. S.} and B. Cantin and {Van Bakel}, A. and G. Ewald and S. Hirt and H. Lehmkuhl and A. Keogh and M. Rinaldi and L. Potena and A. Zuckermann and G. Dong and C. Cornu-Artis and P. Lopez",
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Eisen, H, Kobashigawa, J, Starling, RC, Pauly, DF, Kfoury, A, Ross, H, Wang, SS, Cantin, B, Van Bakel, A, Ewald, G, Hirt, S, Lehmkuhl, H, Keogh, A, Rinaldi, M, Potena, L, Zuckermann, A, Dong, G, Cornu-Artis, C & Lopez, P 2013, 'Everolimus versus mycophenolate mofetil in heart transplantation: A randomized, multicenter trial', American Journal of Transplantation, vol. 13, no. 5, pp. 1203-1216. https://doi.org/10.1111/ajt.12181

Everolimus versus mycophenolate mofetil in heart transplantation : A randomized, multicenter trial. / Eisen, Howard; Kobashigawa, J.; Starling, R. C.; Pauly, D. F.; Kfoury, A.; Ross, H.; Wang, S. S.; Cantin, B.; Van Bakel, A.; Ewald, G.; Hirt, S.; Lehmkuhl, H.; Keogh, A.; Rinaldi, M.; Potena, L.; Zuckermann, A.; Dong, G.; Cornu-Artis, C.; Lopez, P.

In: American Journal of Transplantation, Vol. 13, No. 5, 01.05.2013, p. 1203-1216.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Everolimus versus mycophenolate mofetil in heart transplantation

T2 - A randomized, multicenter trial

AU - Eisen, Howard

AU - Kobashigawa, J.

AU - Starling, R. C.

AU - Pauly, D. F.

AU - Kfoury, A.

AU - Ross, H.

AU - Wang, S. S.

AU - Cantin, B.

AU - Van Bakel, A.

AU - Ewald, G.

AU - Hirt, S.

AU - Lehmkuhl, H.

AU - Keogh, A.

AU - Rinaldi, M.

AU - Potena, L.

AU - Zuckermann, A.

AU - Dong, G.

AU - Cornu-Artis, C.

AU - Lopez, P.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - 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. In this study comparing cardiac transplant recipients receiving one of two doses of everolimus with reduced dose cyclosporine to patients receiving mycophenolate mofetil with standard dose cyclosporine, the authors find no effect on acute cellular rejection, modestly reduced renal function, and a reduction in the incidence and severity of lesions defined by intravascular ultrasound. See editorial by Mehra on page 1119.

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