OPTIMUM MAINTENANCE TROUGH LEVELS OF CYCLOSPORINE IN HEART-TRANSPLANTRECIPIENTS GIVEN CORTICOSTEROID-FREE REGIMEN

Background: Standard immunosuppressive therapy for heart transplant re cipients consists of cyclosporine, azathioprine, and corticosteroids. Long-term use of steroids results in serious side effects. Steroid-fre e maintenance immunosuppressive regimens have been shown to be safe an d effective in selected heart transplant recipients. Cyclosporine is t he cornerstone of immunosuppressive therapy in such regimens. The idea l dose of cyclosporine, providing adequate immunosuppression while min imizing toxicity, remains controversial in the standard triple immunos uppressive regimen. This study attempted to define the optimal level o f cyclosporine (whole blood radioimmunoassay) for heart transplant rec ipients given a steroid-free regimen. Methods: We retrospectively anal yzed data from 583 endomyocardial biopsies and corresponding cyclospor ine trough levels obtained from 48 orthotopic heart transplant recipie nts maintained without steroids. We used maximum Likelihood probit tec hniques to examine the correlation between cyclosporine level and the probability of rejection (International Society for Heart and Lung Tra nsplantation [ISHLT] grades higher than 1A), The data were adjusted fo r age at the time of transplantation, sex, race, time elapsed since tr ansplantation, and azathioprine dose. Results: Higher cyclosporine lev els were associated with a lower probability of acute cellular rejecti on (p < .03). The lowest probability of rejection, ISHLT grades higher than 1A (1.7%), was associated with a cyclosporine level of 322 ng/mL . In this database, higher levels of cyclosporine were not associated with higher serum creatinine levels (p = .6). Conclusions: Cyclosporin e trough levels of 300 to 350 ng/mL (whole blood radioimmunoassay) are associated with the lowest probability of cellular rejection in patie nts given a steroid-free regimen of cyclosporine and azatkioprine. The re was no association between cyclosporine levels and serum creatinine .