Maintenance immunosuppression with mycophenolate mofetil: long-term efficacy and safety after heart transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is superior to azathioprine (AZA) in preventing allograft rejections episodes (ARE) early after heart transplantation (HTx). However, long-term efficacy and adverse events are barely known. We evaluated the long-term efficacy and safety, comparing patient outcomes with either MMF or AZA as components of maintenance immunosuppression regimens.

METHODS: We evaluated all patients who underwent HTx between January 1994 and May 2003 and received the same induction immunosuppression followed by treatment with cyclosporine (CsA), prednisolone, and with either MMF or AZA. We analyzed the survival, number, and severity of ARE, development of coronary allograft vasculopathy (CAV), and main adverse effects (infections, tumors).

RESULTS: Patients receiving MMF (n = 137) showed a lower mortality rate than those treated with AZA (n = 121). There were significant differences between the groups for all parameters evaluated (P < .01). The prevalence of deaths was 18.3% in the MMF group and 47.9% in the AZA group. Biopsy-proven ARE greater than grade 1A and antirejection therapies per patient were lower among the MMF than the AZA group (0.20 vs 0.31 and 0.96 vs 1.24, respectively). Prevalence of coronary stenoses was 11.7% in the MMF group and 24.8% in the AZA group. Rate of extracutaneous and cutaneous malignancies was lower in the MMF than the AZA group (7.3% and 5.8% vs 18.2% and 9.1%, respectively). The prevalence of infections was higher in the MMF group. Patients who were switched during the first post-HTx year from AZA to MMF (n = 97) and thereafter received CsA plus MMF for >1 year also showed significantly better survival than those who remained on AZA treatment.

CONCLUSIONS: Among a cohort of patients being followed long term, MMF appeared to be highly efficient to prevent both ARE and the development of coronary artery stenoses. The use of MMF also significantly improved the survival of heart transplant recipients compared with AZA, despite a greater incidence of infections linked to MMF therapy.