Early vs. Delayed EVERolimus in De Novo HEART Transplant Recipients

Multicenter clinical trials showed that everolimus (EVE) associated with low dose cyclosporine (CSA) is superior to azathioprine and equivalent to mycophenolate (MMF) in preventing myocardial acute rejection in de novo heart recipients. In addition, data from randomized and non-randomized studies suggest that EVE may have ancillary properties that may favorably impact long-term survival, by reducing the progression of allograft vasculopathy, the incidence of cytomegalovirus infection, and the onset of post-transplant malignancies. Nonetheless, EVE safety profile still needs to be optimized in particular in the early post-surgery phase, because of a worsening renal function when used with full-dose CSA, and because EVE anti-proliferative properties may delay surgical wound healing and increase the risk for pleural and pericardial effusions. The purpose of this 6-month, controlled, randomized study in de novo heart transplant patients is to compare the occurrence of a composite safety enpoint between a strategy based on delayed introduction of EVE – with MMF as a 4 to 6 weeks bridge in the post-transplant period – and EVE started within post-operative day 5. EVE start dose is adjusted according with some patients' characteristics potentially associated with EVE-related adverse events