title: Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.
abstract: Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.
authors.affiliation: Unidad de Transplante Cardiaco, Hospital Universitario Puerta de Hierro, Madrid, Spain. jsecu@eresmas.net
authors.forename: Javier
authors.initials: J
authors.lastname: Segovia
authors.forename: Gino
authors.initials: G
authors.lastname: Gerosa
authors.forename: Luis
authors.initials: L
authors.lastname: Almenar
authors.forename: Ugolino
authors.initials: U
authors.lastname: Livi
authors.forename: Mario
authors.initials: M
authors.lastname: Viganò
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Arizón
authors.forename: Nizar
authors.initials: N
authors.lastname: Yonan
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Di Salvo
authors.forename: Dale G
authors.initials: DG
authors.lastname: Renlund
authors.forename: Jon A
authors.initials: JA
authors.lastname: Kobashigawa
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000401:mortality; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011183:Postoperative Complications; D016037:Single-Blind Method; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage; D013810:Therapeutic Equivalency; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013608:Tablets, Enteric-Coated; D009173:Mycophenolic Acid