title: A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators.
abstract: BACKGROUND
  After heart transplantation, 1-year and 5-year survival rates are 79% and 63%, respectively, with rejection, infection, and allograft coronary artery disease accounting for the majority of deaths. Mycophenolate mofetil (MMF), an inhibitor of the de novo pathway for purine biosynthesis, decreases rejection in animals and in human renal transplantation.
  
  
  METHODS
  In a double-blind, active-controlled trial, 28 centers randomized 650 patients undergoing their first heart transplant to receive MMF (3000 mg/day) or azathioprine (1.5-3 mg/kg/day), in addition to cyclosporine and corticosteroids. Rejection and survival data were obtained for 6 and 12 months, respectively. Because 11% of the patients withdrew before receiving study drug, data were analyzed on all randomized patients (enrolled patients) and on patients who received study medications (treated patients).
  
  
  RESULTS
  Survival and rejection were similar in enrolled patients (MMF, n=327; azathioprine, n=323). In treated patients (MMF, n=289; azathioprine, n=289), the MMF group compared with the azathioprine group was associated with significant reduction in mortality at 1 year (18 [6.2%] versus 33 deaths [11.4%]; P=0.031) and a significant reduction in the requirement for rejection treatment (65.7% versus 73.7%; P=0.026). There was a trend for fewer MMF patients to have > or = grade 3A rejection (45.0% versus 52.9%; P=0.055) or require the murine monoclonal anti-CD3 antibody or antithymocyte globulin (15.2% versus 21.1%; P=0.061). Opportunistic infections, mostly herpes simplex, were more common in the MMF group (53.3% versus 43.6%; P=0.025).
  
  
  CONCLUSIONS
  Substitution of MMF for azathioprine may reduce mortality and rejection in the first year after cardiac transplantation.
authors.affiliation: University of California, Los Angeles, USA.
authors.forename: J
authors.initials: J
authors.lastname: Kobashigawa
authors.forename: L
authors.initials: L
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Renlund
authors.forename: R
authors.initials: R
authors.lastname: Mentzer
authors.forename: E
authors.initials: E
authors.lastname: Alderman
authors.forename: R
authors.initials: R
authors.lastname: Bourge
authors.forename: M
authors.initials: M
authors.lastname: Costanzo
authors.forename: H
authors.initials: H
authors.lastname: Eisen
authors.forename: G
authors.initials: G
authors.lastname: Dureau
authors.forename: R
authors.initials: R
authors.lastname: Ratkovec
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: D
authors.initials: D
authors.lastname: Ipe
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: A
authors.initials: A
authors.lastname: Keogh
authors.forename: R
authors.initials: R
authors.lastname: Mamelok
authors.forename: D
authors.initials: D
authors.lastname: Mancini
authors.forename: F
authors.initials: F
authors.lastname: Smart
authors.forename: H
authors.initials: H
authors.lastname: Valantine
mesh_terms: D000368:Aged; D001379:Azathioprine / Q000627:therapeutic use*; D017023:Coronary Angiography; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000000981:diagnostic imaging / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D015996:Survival Rate; D014463:Ultrasonography
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine