Abstract 17448: Tacrolimus with Mycophenolate Mofetil (MMF) or Sirolimus Compared with Calcineurininhibitor-Free Immunosuppression (Sirolimus/MMF) after Heart Transplantation: 5-Year Results
Background: Despite significant improvements in immunosuppressive therapy over the past decades the most advantageous combination for long-term outcome for cardiac transplant recipients has not yet been established. Therefore, we performed a randomized controlled trial to evaluate the efficacy and safety of three immunosuppressive protocols.
Methods: Between April 2003 and October 2005, 78 de novo cardiac transplant recipients were randomized on a 2:2:1 basis to receive steroids and either tacrolimus (TAC) + mycophenolate mofetil (MMF) (n=34), TAC + sirolimus (SRL) (n=29), or SRL + MMF (n=15). Steroids were withdrawn after 6 months. All patients received statins.
Results: Cumulative survival at 5 years was: 85.3% in the TAC/MMF group, 93.1% in the TAC/SRL group, and 86.7% in the SRL/MMF group (p=ns). Freedom from acute rejection episodes (AREs) at 5 years was not statistically different between the groups: TAC/MMF 81.3%, TAC/SRL 85.2%, SRL/MMF 73.3% (p=ns). Mean levels of serum creatinine at 5 years revealed a superior preservation of renal function in the SRL/MMF vs. the TAC/MMF group (p = 0.045): TAC/MMF = 1.70 ± 0.91 mg/dL, TAC/SRL = 1.44 ± 0.65 mg/dL and SRL/MMF = 1.25 ± 0.46 mg/dL. Freedom form cardiac allograft vasculopathy (CAV) was: TAC/MMF 73.5%, TAC/SRL 80.8%, and SRL/MMF 93.3% revealing a trend towards superior freedom from CAV with SRL/MMF compared to the TAC/MMF group (p = 0.090). Freedom from CMV infection was: TAC/MMF 72.2%, TAC/SRL 89.7%, and SRL/MMF 86.7%. There was a trend towards superior freedom form CMV infection with TAC/SRL when compared only to the TAC/MMF group (p = 0.076). Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride serum levels at 5 years revealed no significant differences. Freedom from study discontinuation due to side effects was significantly higher in the TAC/MMF groups vs. the TAC/SRL (p = 0.034) and the SRL/MMF (p = 0.003) groups.
Conclusions: Both tacrolimus groups proved to be efficacious for the prevention of acute rejection. The side effect profile for the SRL groups is inferior to the TAC/MMF group resulting in a high discontinuation rate while the calcineurininhibitor-free protocol results in a lower incidence of vasculopathy and preserves renal function.
- © 2012 by American Heart Association, Inc.