The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy. 1. Introduction The mammalian target-of-rapamycin inhibitor (mTOR) everolimus has been licensed in Europe since 2004 for the prevention of organ rejection in adult patients at low to moderate immunological risk receiving an allogeneic kidney, liver or heart transplant. Everolimus is currently the only mTOR inhibitor approved for use in heart transplantation. It was developed to improve the pharmacokinetics of the mTOR inhibitor sirolimus through a stable 2-hydroxyethyl chain substitution at position 40 of the sirolimus molecule [1]. This change confers a shorter half-life, permitting faster reduction or elimination of everolimus exposure and obviating the need for a loading dose. In a pivotal double-blind phase 3 (B253) trial in de novo heart transplant recipients published in 2003, Eisen et al. demonstrated that everolimus provided equivalent immunosuppressive efficacy to azathioprine [2]. Inhibition of vascular smooth muscle cell proliferation by everolimus reduced intimal thickening and lowered the incidence of cardiac allograft vasculopathy (CAV). Based on these findings and early clinical experience in Germany and Austria,
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