Purpose: to estimate the outcomes of patients managed with everolimus (EVL) after heart transplantation (HTx).
Materials and methods: From January 2010 to November 2019 it was performed 134 HTx (46±14 yrs-old, n=99 – male). Patients were managed with triple-drug therapy (tacrolimus (TAC), mycophenolate mofetil (MMF), steroids) plus induction (basiliximab – 81%; thymoglobulin – 15%; no induction – 4%). We retrospectively estimated outcomes of EVL treated patients.
Results: From 1 month to 6 years after HTx immunosuppressive regimen was changed to concentration-controlled EVL (initial dose 1.5 mg/day, C0 target 3-8 ng/ml) and reduced-exposure TAC in 28% (n=37) of patients (51±13 yrs-old; n=26 - male). Basiliximab was used as an induction therapy in 33 of them. There was no de novo use of EVL following HTx. Indications for EVL treatment were as follows: chronic kidney disease (CKD; n=24), cardiac allograft vasculopathy (CAV; n=10), progression of atherosclerosis (n=2), oncology (n=1 – breast cancer prior to HTx; n=6 after HTx: 1 – lung cancer, 1 – basal cell carcinoma, 4 – colorectal polyps), severe leucopenia (n=3) and clinically significant tremor (n=2). Seven patients had a few indications or they were developed after recipients were switched to EVL therapy. EVL was discontinued in 7 patients from 3 to 6 months after conversion due to infectious complications (n=5: 4 - pneumonia, 1 - acute cholecystitis with subhepatic abscess), interstitial pneumonitis (IP; n=3: 2 – one month after initiated treatment), steroid-resistant and recurrent rejection (n=2). IP was successfully managed with 1-3 months steroid treatment. Due to the frequency of infectious complications our C0 target for everolimus - 3.0-6.5 ng/ml. There was no difference in a frequency of rejection between patients on TAC+MMF or rTAC+EVL. In 14% (n=5) of recipients dyslipidemia progressed and in 2 of them it was normalized only after the combination of atorvastatin (20mg/per day) plus fenofibrate (145 mg/per day). Leucopenia has been noted in 5 patients but only 2 of them had indications for CSFs management. Creatinine normalized only in 4 from 24 recipients. Despite EVL treatment we registered the progression of CAV, atherosclerosis or the onset of oncology in 17% of cases. Four EVL treated recipients died due to VFib (n=2; also associated with AKI and infectious complications), chronic rejection, CAV (n=1) and lung cancer (n=1).
Conclusion: One-fourth of patients were managed with EVL. Frequent indications for EVL were CKD and CAV. Concentration-controlled EVL (C0 target 3.0-6.5 ng/ml) in combination with reduced TAC achieved good efficacy and safety, higher C0 target was associated with frequent infectious complications. Patients need to be screened for EVL adverse effects, especially during first 6 months.