Long‐term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open‐label, randomized trial

Lars Gullestad, Hans Eiskjaer, Finn Gustafsson, Gerdt C Riise, Kristjan Karason, Göran Dellgren, Göran Rådegran, Lennart Hansson, Einar Gude, Øystein Bjørtuft, Kjell Jansson, Hans Henrik Schultz, Dag Solbu, Martin Iversen

The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years post-randomization (mean 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3mL/min) to last visit (51.4mL/min) but decreased in controls (from 50.5mL/min to 45.3mL/min), and was significantly higher with everolimus at last follow-up (p=0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)mL/min with everolimus versus -7.2 (1.7)mL/min for controls (difference 5.7 [95% CI 1.7; 9.6]mL/min; p=0.006). The difference was accounted for by heart transplant patients (difference 6.9 [95% 2.3; 11.5]mL/min; p=0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% versus 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least five years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained. This article is protected by copyright. All rights reserved.