title: Low-dose tacrolimus/sirolimus and steroid withdrawal in heart recipients is highly efficacious.
abstract: 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 Steroids were withdrawn successfully from all patients within 6 months.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.
authors.affiliation: Department of Cardiac Surgery, Ludwig Maximilian University, Munich, Germany. bruno.meiser@med.uni-muenchen.de
authors.forename: Bruno
authors.initials: B
authors.lastname: Meiser
authors.forename: Ingo
authors.initials: I
authors.lastname: Kaczmarek
authors.forename: M
authors.initials: M
authors.lastname: Mueller
authors.forename: Jan
authors.initials: J
authors.lastname: Groetzner
authors.forename: Michael
authors.initials: M
authors.lastname: Weis
authors.forename: Andreas
authors.initials: A
authors.lastname: Knez
authors.forename: Hans-Ullrich
authors.initials: HU
authors.lastname: Stempfle
authors.forename: Volker
authors.initials: V
authors.lastname: Klauss
authors.forename: Michael
authors.initials: M
authors.lastname: Schmoeckel
authors.forename: Bruno
authors.initials: B
authors.lastname: Reichart
authors.forename: Peter
authors.initials: P
authors.lastname: Ueberfuhr
mesh_terms: 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
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus