1. Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes
- Author
-
González-Vílchez F., Crespo-Leiro M.G., Delgado-Jiménez J., Pérez-Villa F., Segovia-Cubero J., Díaz-Molina B., Mirabet-Pérez S., Arizón del Prado J.M., Blasco-Peiró T., Martínez-Sellés M., Almenar-Bonet L., Garrido-Bravo I., Rábago G., and Vázquez de Prada J.A.
- Subjects
Adult ,Graft Rejection ,all cause mortality ,Adolescent ,retrospective study ,Calcineurin Inhibitors ,education ,mortality rate ,treatment free survival ,heart transplantation ,blood level ,behavioral disciplines and activities ,Article ,Tacrolimus ,male ,genetic variability ,middle aged ,mental disorders ,calcineurin inhibitor ,Humans ,controlled study ,cyclosporine ,human ,Retrospective Studies ,Blood levels, Calcineurin inhibitors, Coefficient of variation, Coeficiente de variación, Concentración sanguínea, Heart transplant, Inhibidores de la calcineurina, Trasplante cardiaco, Variabilidad, Variability ,cardiac graft rejection ,disease association ,immunosuppressive treatment ,social sciences ,immunosuppressive agent ,major clinical study ,human tissue ,drug formulation ,female ,surgical procedures, operative ,treatment outcome ,heart graft ,Immunosuppressive Agents - Abstract
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. Full English text available from:www.revespcardiol.org/en © 2021 Sociedad Española de Cardiología
- Published
- 2021