A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients

Jon Kobashigawa, Leslie Miller, Dale Renlund, Robert Mentzer, Edwin Alderman, Robert Bourge, Maria Costanzo, Howard Eisen, Georges Dureau, Ranae Ratkovec, Manfred Hummel, David Ipe, Jay Johnson, Anne Keogh, Richard Mamelok, Donna Mancini, Frank Smart, Hannah Valantine

Research output: Contribution to journalArticlepeer-review

539 Scopus citations


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 ≤ 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.

Original languageEnglish (US)
Pages (from-to)507-515
Number of pages9
Issue number4
StatePublished - Aug 27 1998

All Science Journal Classification (ASJC) codes

  • Transplantation


Dive into the research topics of 'A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients'. Together they form a unique fingerprint.

Cite this