A RANDOMIZED ACTIVE-CONTROLLED TRIAL OF MYCOPHENOLATE-MOFETIL IN HEART-TRANSPLANT RECIPIENTS

Background. After heart transplantation, 1-year and 5-year survival ra tes are 79% and 63%, respectively, with rejection, infection, and allo graft coronary artery disease accounting for the majority of deaths. M ycophenolate mofetil (MMF), an inhibitor of the de novo pathway for pu rine biosynthesis, decreases rejection in animals and in human renal t ransplantation. Methods. In a double-blind, active-controlled trial, 2 8 centers randomized 650 patients undergoing their first heart transpl ant 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 t he patients withdrew before receiving study drug, data were analyzed o n all randomized patients (enrolled patients) and on patients who rece ived study medications (treated patients). Results. Survival and rejec tion were similar in enrolled patients (MMF, n=327; azathioprine, n=32 3), In treated patients (MMF, n=289; azathioprine, n=289), the MMF gro up compared with the azathioprine group was associated with significan t 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 rejectio n treatment (65.7% versus 73.7%; P=0.026). There was a trend for fewer MMF patients to have greater than or equal to grade 3A rejection (45. 0% versus 52.9%; P=0.055) or require the murine monoclonal anti-CD3 an tibody or antithymocyte globulin (15.2% versus 21.1%; P=0.061). Opport unistic 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.