Low-dose tacrolimus/sirolimus and steroid withdrawal in heart recipients is highly efficacious.
Heart transplant recipients treated with long-term calcineurin inhibitors (CNIs) experience significant nephrotoxicity and transplant vasculopathy. Signal proliferation inhibitors might prevent the development of transplant vasculopathy. In an open, prospective pilot study, 33 primary heart transplant recipients received tacrolimus (Tac) and sirolimus (rapamycin, Rapa) with steroids. To reduce both nephrotoxicity and transplant vasculopathy at the same time, both Tac and Rapa exposure was kept low (6 to 8 ng/ml). Steroids were withdrawn successfully from all patients within 6 months. Just one acute rejection occurred at 54 days post-transplant, resulting in 0.03 acute rejection episode per patient at 1-year (primary end-point) and 2-year follow-up. Transplant vasculopathy assessed by angiogram was absent at 2 years. Graft and patient survival were 100% at 1 and 2 years. Accordingly, the survival estimate for freedom from first acute rejection, transplant vasculopathy, graft loss or death was 0.97 at 1 and 2 years. The regimen was well tolerated with only 3 patients requiring a change of study medication. Mean serum creatinine increased during the first year but returned to baseline at 2 years.
Meiser
Bruno
B
Department of Cardiac Surgery, Ludwig Maximilian University, Munich, Germany. bruno.meiser@med.uni-muenchen.de
Kaczmarek
Ingo
I
Mueller
M
M
Groetzner
Jan
J
Weis
Michael
M
Knez
Andreas
A
Stempfle
Hans-Ullrich
HU
Klauss
Volker
V
Schmoeckel
Michael
M
Reichart
Bruno
B
Ueberfuhr
Peter
P
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology; D006333:Heart Failure / Q000601:surgery; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007239:Infections; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control; D011446:Prospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D013997:Time Factors
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus