Everolimus and reduced cyclosporine trough levels in maintenance heart transplant recipients.
BACKGROUND
Long-term survival of patients after oHTX significantly increased over the last years, but CAV and chronic renal failure due to nephrotoxic side-effects of CNIs still remain unsolved problems. Everolimus has shown to reduce acute cellular rejection and may allow CsA dosage reduction. In this study the effectiveness of Everolimus in combination with CsA dosage reduction in maintenance oHTX immunosuppression and the influence on renal function was tested.


METHODS
37 patients (30 male, 7 female) after oHTX were divided into group A (n = 20) receiving Everolimus in combination with CsA and prednisolone and group B (n = 17) under standard immunosuppression with CsA, MMF and prednisolone. Patients received 1.0 mg to 1.5 mg Everolimus per day and target Everolimus trough levels were between 3 and 8 ng/ml. Death, safety, side effects, BPAR, trough levels, and routine laboratory values especially creatinine levels were monitored over a follow-up period of 8 months retrospectively and statistically evaluated.


RESULTS
A significant reduction of CsA dosage (p < 0.001) and a significant CsA trough level reduction (p < 0.001) to a median CsA trough level of 68.5 ng/ml were achieved in group A. Mean Everolimus trough levels were reached within 1 week and 2 months. Renal function was stable in both groups. No statistical differences in BPAR, hospitalization rates or triglyceride levels were observed. Cholesterol levels significantly increased in group B (p = 0.024).


CONCLUSIONS
CsA trough levels and dosage can be significantly reduced in combination with Everolimus without higher rejection rates and with stable kidney function in oHTX patients.
Schweiger
Martin
M
Department of Surgery, Division of Transplantation Surgery, Medical University Graz, Austria. martin.schweiger@klinikum-graz.at
Wasler
Andre
A
Prenner
Guenther
G
Stiegler
Philipp
P
Stadlbauer
Vanessa
V
Schwarz
Michaela
M
Tscheliessnigg
Karlheinz
K
D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D006084:Graft Rejection / Q000503:physiopathology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus