The CECARI Study: Everolimus (Certican®) Initiation and Calcineurin Inhibitor Withdrawal in Maintenance Heart Transplant Recipients with Renal Insufficiency: A Multicenter, Randomized Trial.

Jan Van Keer,Johan Van Cleemput,Nathalie Duerinckx,Johan Vanhaecke,Bart Meyns,Gábor Vörös,Eric Nellessen,David Derthoo,Stefan Janssens,Walter Droogne,Michel De Pauw,Ann Belmans,Olivier Van Caenegem

doi:10.1155/2017/6347138

Abstract

In this 3-year, open-label, multicenter study, 57 maintenance heart transplant recipients (>1 year after transplant) with renal insufficiency (eGFR 30–60 mL/min/1.73 m2) were randomized to start everolimus with CNI withdrawal (N = 29) or continue their current CNI-based immunosuppression (N = 28). The primary endpoint, change in measured glomerular filtration rate (mGFR) from baseline to year 3, did not differ significantly between both groups (+7.0 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.18). In the on-treatment analysis, the difference did reach statistical significance (+9.4 mL/min in the everolimus group versus +1.9 mL/min in the CNI group, p = 0.047). The composite safety endpoint of all-cause mortality, major adverse cardiovascular events, or treated acute rejection was not different between groups. Nonfatal adverse events occurred in 96.6% of patients in the everolimus group and 57.1% in the CNI group (p < 0.001). Ten patients (34.5%) in the everolimus group discontinued the study drug during follow-up due to adverse events. The poor adherence to the everolimus therapy might have masked a potential benefit of CNI withdrawal on renal function.

Highlights

Calcineurin inhibitors (CNIs) have made an invaluable contribution to the improvement of short and mid-term survival after heart transplantation [1]
CNIs contribute to metabolic disturbances such as posttransplant diabetes mellitus, dyslipidemia, and hypertension and predispose to posttransplant malignancies and infection [4, 5]
Except for a higher proportion of patients receiving loop diuretics in the everolimus group (44.8% versus 10.7%, p = 0.004), concomitant medication was similar

Summary

Introduction

Calcineurin inhibitors (CNIs) have made an invaluable contribution to the improvement of short and mid-term survival after heart transplantation [1]. Their use is associated with significant long-term side effects. One in ten heart transplant recipients will develop end stage renal failure, which is associated with a more than fourfold increase in mortality [2, 3]. CNIs contribute to metabolic disturbances such as posttransplant diabetes mellitus, dyslipidemia, and hypertension and predispose to posttransplant malignancies and infection [4, 5]. CNIs do not prevent the development cardiac allograft vasculopathy (CAV) [6]

Methods

Results

Conclusion