Detalle Publicación

Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes

Autores: González-Vilchez, F. (Autor de correspondencia); Crespo-Leiro, M. G.; Delgado-Jiménez, J.; Pérez-Villa, F.; Segovia-Cubero, J.; Diaz-Molina, B.; Mirabet-Pérez, S.; Arizón del Prado, J. M. ; Blasco-Peiro, T.; Martínez-Selles, M.; Almenar-Bonet, L.; Garrido-Bravo, I.; Rabago Juan Aracil, Gregorio; Vázquez de Prada, J. A.
ISSN: 0300-8932
Volumen: 75
Número: 2
Páginas: 129 - 140
Fecha de publicación: 2022
Introduction and objectives: Intrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. Methods: We retrospectively studied patients aged >= 18 years, with a first heart transplant performed between 2000 and 2014 and surviving >= 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. Results: The study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation > 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P = .056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P = .065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P = .011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. Conclusions: IPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients.