CONGRESS ABSTRACT

SA.RE.FU is a single-centre, prospective, randomized clinical trial which enrolled adult heart transplant patients in Hospital Papa Giovanni XXIII, Bergamo. The study began in 2007, with the aim to verify whether the reduction of cyclosporine dosages associated with everolimus administration may improve renal function as compared to patients maintained on standard immunosuppressive therapy. Heart transplant patients with more than 1 year of follow-up, with creatinine < 3.5 mg/dl and eGFR > 20 ml/min (calculated with Cockcroft-Gault formula) and without prior history of acute rejection within the last 3 months were enrolled and randomized to standard therapy vs everolimus combined with cyslosporine, whose dosage was reduced of 50% after introduction of everolimus. The primary endpoint was renal function, estimated with creatinine, creatinine clearance (MDRD and Cockcroft-Gault) and urinary excretion of protein, albumin and alpha-1-microglobulin. Secondary endpoints were all cause mortality, infections, incidence of acute myocardial rejection, heart failure, chronic rejection and MACE. 213 patients were enrolled, 106 in the control group and 107 in the intervention group. Mean age of patients was 52.6 years, with a mean time from heart transplant of 8.8 years; female were 45 (21%), 110 patients (52%) had dilated cardiomyopathy and 51 had ischemic cardiomyopathy (24%). At baseline mean creatinine was 1.61mg/dl, with an mean eGFR 61.8ml/min/1.73m2 and a mean uACR 220mg/g; 116 patients (54%) had chronic kidney disease of at least stage III (based on eGFR values). At baseline, 47 patients (23%) had cardiac allograft vasculopathy (CAV). After 2 years of follow-up, the mean difference of eGFR between the two groups was 4.4 ml/min/1.73m2 and 6.3 ml/min/1.73m2 (respectively, with Cockcroft-Gault and MDRD formula) with better values in the everolimus group, in which, however, uACR was higher with a mean difference of 70.4mg/gr compared to stardard therapy. In the standard therapy group, mean daily dosage of cyclosporine was 2.54mg/kg with C0-levels of 171 ng/mL compared to mean daily dosage of 1.04mg/kg with C0-levels of 60ng/mL in the everolimus group (respectively, 40% and 35% of standard therapy). The mean dose of everolimus was 1.3mg/day with a mean plasmatic levels of 7.8 ng/mL. Only 15 patients (7%) were on steroid therapy, 35 (16%) had mofetil mycophenolate and 53 (25%) were on azathioprine.