1. EVEROLIMUS IN LATE IMMUNOSUPPRESSION AFTER HEART TRANSPLANTATION:
IN SEARCH OF THE RIGHT PROTOCOL FOR THE RIGHT PATIENT.
Federica Agrusta1, Daniela Pinto1, Emanuele Durante1, Gianpaolo Romano2, Claudio Marra2, Ciro Maiello2, Riccardo Utili1, Cristiano Amarelli2
1 Internal Medicine of Transplants, Second University of Naples- Az dei Colli. Naples
2 Cardiovascular Surgery and Transplants, Monaldi Hospital- Az dei Colli. Naples
Background
Everolimus is a potent novel immunosuppressor with a powerful antiproliferative effect and an intriguing mechanism of action. Its antiproliferative effect has been advocated as an unique therapeutic tool in the treatment and prevention of Cardiac Allograft Vasculopathy, in prevent neoplasms and PTLD and as a strategy to minimize CNI exposure and the related renal toxicity.
Aim of the study is to describe the effect of the introduction of the Eve on the results of the management of the most common complications of heart transplantation.
Material and Methods
Since 2005, Eve has been introduced in the immunosuppressive therapy as maintenance therapy in 71 patients. Both the timing and clinical indications have been registered.
The switch to eve was in 30,9% for CAV, in 18,6% for CRF, and in 22,5% for neoplastic disorders (PTLD or solid). CNI Minimization was the most frequent regimen; a CNI-free regimen was maintained in 8 patients (11,6%).
The mean follow-up was 46,8±25 while the mean time between the transplant and the switch to everolimus was 82,5±48,3 months.

2. Excellent survival up to 88% at 3 years and 84% at 5 years.
Results
No cases of discontinuation were disclosed (2 suspension for temporary leucopenia).
Excellent survival up to 88% at 3 years and 84% at 5 years.
Incidence of dyalisis was 8,45% with an actuarial freedom of 80,6% at 3 years.
GFR after the switch did not ameliorate as expected but in the early experience proteinuria was never assessed and the switch was probably performed too late (mean GFR at the switch of patients undergoing dialysis 22,77±11,9).
No patients experienced Acute Cellular Rejection nor Humoral rejection despite the lower level of Cyclosporine (CSA-TL).
The freedom from dialysis was 80,6% at 3 years in the maintenance group.
GFR at the switch was:
56,85±24,7 NOT dialysis vs 22,77 dialysis; p=0,003
When Eve was used with aims different from renal failure the best renal outcomes were achieved.
It has to be note how GFR at the switch differs relate to the indication:
52,01±18,77 in Neoplastic/PTLD patients
44,42±18,66 in patients affected from CAV
29,12±11,47 in patient switched for CRF
and also the time between transplant and switch although not significantly:
CAV 97,4±46,2
CRF 83,1±35,7
PTLD 75,3± 49,1
Other 66,6±52,2

3. Results
A significantly more aggressive reduction of CSA TL was disclosed in the patients with a stable or ameliorating renal function when compared with the patients experiencing a reduction of GFR after 1 year of treatment (50% of Pts).
CSA TL in patients treated with Everolimus
(GFR stable vs worsening after 1 year)
Discussion
In the long-term Eve warrant an excellent protection from both late and acute rejection, alone or in combination with CNI or MMF.
In consideration of the low incidence of allograft dysfunction or rejection and of the better renal protection achieved when CSA TL is aggressively reduced more efforts have to be done in the long term therapy to reduce the TL of cyclosporine.