Scientific publications
Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes
Francisco González-Vílchez 1 , María G Crespo-Leiro 2 , Juan Delgado-Jiménez 3 , Félix Pérez-Villa 4 , Javier Segovia-Cubero 5 , Beatriz Díaz-Molina 6 , Sonia Mirabet-Pérez 7 , José María Arizón Del Prado 8 , Teresa Blasco-Peiró 9 , Manuel Martínez-Sellés 10 , Luis Almenar-Bonet 11 , Iris Garrido-Bravo 12 , Gregorio Rábago 13 , José Antonio Vázquez de Prada 14
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.
CITATION Rev Esp Cardiol (Engl Ed). 2022 Feb;75(2):129-140. doi: 10.1016/j.rec.2021.02.001. Epub 2021 Mar 18.