Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial. Issue 8 (10th July 2014)

• Record Type: Journal Article
• Authors: Andreassen, A. K.; Andersson, B.; Gustafsson, F.; Eiskjær, H.; Rådegran, G.; Gude, E.; Jansson, K.; Solbu, D.; Sigurdardottir, V.; Arora, S.; Dellgren, G.; Gullestad, L.; on behalf of the SCHEDULE (Scandinavian heart transplant everolimus de novo study with early calcineurin inhibitors avoidance) Investigators
• Is Part Of: American journal of transplantation. Volume 14:Issue 8(2014:Aug.)
• Page Start: 1828
• Page End: 1838
• Publication Date: 2014-07-10
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.12809
• Languages: English
• ISSNs: 1600-6135

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajt12809-sec-0001" sec-type="section"> <p>In a randomized, open‐label trial, everolimus was compared to cyclosporine in 115 <italic>de novo</italic> heart transplant recipients. Patients were assigned within 5 days posttransplant to low‐exposure everolimus (3–6 ng/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 In the everolimus group, cyclosporine was withdrawn after 7–11 weeks and everolimus exposure increased (6–10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean ± SD: 79.8 ± 17.7 mL/min/1.73 m<sup>2</sup> vs. 61.5 ± 19.6 mL/min/1.73 m<sup>2</sup>; p < 0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], 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.</p> </sec> </abstract>