Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART.

Background: Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. Methods: This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion (PCEs), pleural effusion (PLEs) needing drainage, and renal insufficiency events (estimated glomerular filtration rate [eGFR] = 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint. Results: Overall, 181 patients were randomized to the EVR-I (n=89) or EVR-D (n=92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P=0.104), mainly driven by a higher rate of PCEs (33.7% vs 19.6%; P=0.04); wound healing delays, acute renal insufficiency events, and PLEs occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm vs EVR-D arm (37.1% vs 28.3%; P=0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm vs EVR-D arm (P=0.02). Conclusions: Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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