title: Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial.
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.
authors: Division of Cardiology, Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, PA, USA. heisen@drexelmed.edu
authors: H J
authors: HJ
authors: Eisen
authors: J
authors: J
authors: Kobashigawa
authors: R C
authors: RC
authors: Starling
authors: D F
authors: DF
authors: Pauly
authors: A
authors: A
authors: Kfoury
authors: H
authors: H
authors: Ross
authors: S-S
authors: SS
authors: Wang
authors: B
authors: B
authors: Cantin
authors: A
authors: A
authors: Van Bakel
authors: G
authors: G
authors: Ewald
authors: S
authors: S
authors: Hirt
authors: H
authors: H
authors: Lehmkuhl
authors: A
authors: A
authors: Keogh
authors: M
authors: M
authors: Rinaldi
authors: L
authors: L
authors: Potena
authors: A
authors: A
authors: Zuckermann
authors: G
authors: G
authors: Dong
authors: C
authors: C
authors: Cornu-Artis
authors: P
authors: P
authors: Lopez
mesh_terms: D000208:Acute Disease; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D001208:Asia / Q000453:epidemiology; D001315:Australia / Q000453:epidemiology; D001706:Biopsy; D004305:Dose-Response Relationship, Drug; D005060:Europe / Q000453:epidemiology; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009206:Myocardium / Q000473:pathology; D009656:North America / Q000453:epidemiology; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013020:South America / Q000453:epidemiology; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus