Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients: A randomized trial

Abstract

In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6ng/mL) with reduced-exposure cyclosporine (n=56), or standard-exposure cyclosporine (n=59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean±SD: 79.8±17.7mL/min/1.73m2 vs. 61.5±19.6mL/min/1.73m 2; p<0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03mm [95% CI 0.01, 0.05mm] vs. 0.08mm [95% CI 0.05, 0.12mm], p=0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p=0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p=0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p<0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome. This randomized, open-label trial in 115 de novo heart transplant recipients shows that low-exposure everolimus (3-6 ng/mL) combined with reduced-exposure cyclosporine withdrawn at 7-11 weeks results in significantly better renal function at 12 months versus standard-exposure cyclosporine. See editorial by Kobashigawa and Zuckerman on page 1719. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.