Optimum maintenance trough levels of cyclosporine in heart transplant recipients given corticosteroid-free regimen.
BACKGROUND
Standard immunosuppressive therapy for heart transplant recipients consists of cyclosporine, azathioprine, and corticosteroids. Long-term use of steroids results in serious side effects. Steroid-free maintenance immunosuppressive regimens have been shown to be safe and effective in selected heart transplant recipients. Cyclosporine is the cornerstone of immunosuppressive therapy in such regimens. The ideal dose of cyclosporine, providing adequate immunosuppression while minimizing toxicity, remains controversial in the standard triple immunosuppressive regimen. This study attempted to define the optimal level of cyclosporine (whole blood radioimmunoassay) for heart transplant recipients given a steroid-free regimen.


METHODS
We retrospectively analyzed data from 583 endomyocardial biopsies and corresponding cyclosporine trough levels obtained from 48 orthotopic heart transplant recipients maintained without steroids. We used maximum likelihood probit techniques to examine the correlation between cyclosporine level and the probability of rejection (International Society for Heart and Lung Transplantation [ISHLT] grades higher than 1A). The data were adjusted for age at the time of transplantation, sex, race, time elapsed since transplantation, and azathioprine dose.


RESULTS
Higher cyclosporine levels were associated with a lower probability of acute cellular rejection (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
Cyclosporine trough levels of 300 to 350 ng/mL (whole blood radioimmunoassay) are associated with the lowest probability of cellular rejection in patients given a steroid-free regimen of cyclosporine and azathioprine. There was no association between cyclosporine levels and serum creatinine.
Nohria
A
A
Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn 06520-8017, USA.
Ehtisham
J
J
Ramahi
T M
TM
D001379:Azathioprine / Q000008:administration & dosage; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D011863:Radioimmunoassay; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D001379:Azathioprine