TY - JOUR
T1 - High tacrolimus trough level variability is associated with rejections after heart transplant
AU - Gueta, Itai
AU - Markovits, Noa
AU - Yarden-Bilavsky, Havatzelet
AU - Raichlin, Eugenia
AU - Freimark, Dov
AU - Lavee, Jacob
AU - Loebstein, Ronen
AU - Peled, Yael
N1 - Publisher Copyright:
© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2018/10
Y1 - 2018/10
N2 - Tacrolimus, the major immunosuppressant after heart transplant (HTx) therapy, is a narrow therapeutic index drug. Hence, achieving stable therapeutic steady state plasma concentrations is essential to ensure efficacy while avoiding toxicity. Whether high variability in steady state concentrations is associated with poor outcomes is unknown. We investigated the association between tacrolimus trough level variability during the first year post-HTx and outcomes during and beyond the first postoperative year. Overall, 72 patients were analyzed for mortality, of whom 65 and 61 were available for rejection analysis during and beyond the first year post-HTx, respectively. Patients were divided into high (median >28.8%) and low tacrolimus level variability (<28.8%) groups. Mean tacrolimus levels did not differ between the groups (12.7 ± 3.4 ng/mL vs 12.8 ± 2.4 ng/mL, P =.930). Patients in the high variability group exhibited higher long-term rejection rate (median total rejection score: 0.33 vs 0, P =.04) with no difference in rejection scores within the first year post-HTx. Multivariate analysis showed that high tacrolimus trough level variability was associated with >8-fold increased risk for any rejection beyond the first year post-HTx (P =.011). Mortality was associated only with cardiovascular complications (P =.018), with no effect of tacrolimus through level variability.
AB - Tacrolimus, the major immunosuppressant after heart transplant (HTx) therapy, is a narrow therapeutic index drug. Hence, achieving stable therapeutic steady state plasma concentrations is essential to ensure efficacy while avoiding toxicity. Whether high variability in steady state concentrations is associated with poor outcomes is unknown. We investigated the association between tacrolimus trough level variability during the first year post-HTx and outcomes during and beyond the first postoperative year. Overall, 72 patients were analyzed for mortality, of whom 65 and 61 were available for rejection analysis during and beyond the first year post-HTx, respectively. Patients were divided into high (median >28.8%) and low tacrolimus level variability (<28.8%) groups. Mean tacrolimus levels did not differ between the groups (12.7 ± 3.4 ng/mL vs 12.8 ± 2.4 ng/mL, P =.930). Patients in the high variability group exhibited higher long-term rejection rate (median total rejection score: 0.33 vs 0, P =.04) with no difference in rejection scores within the first year post-HTx. Multivariate analysis showed that high tacrolimus trough level variability was associated with >8-fold increased risk for any rejection beyond the first year post-HTx (P =.011). Mortality was associated only with cardiovascular complications (P =.018), with no effect of tacrolimus through level variability.
KW - clinical research / practice
KW - drug toxicity
KW - heart transplantation / cardiology
KW - immunosuppressant - calcineurin inhibitor: tacrolimus
KW - organ transplantation in general
KW - pharmacokinetics / pharmacodynamics
KW - pharmacology
KW - rejection
KW - risk assessment / risk stratification
UR - http://www.scopus.com/inward/record.url?scp=85052635677&partnerID=8YFLogxK
U2 - 10.1111/ajt.15016
DO - 10.1111/ajt.15016
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 29989311
AN - SCOPUS:85052635677
SN - 1600-6135
VL - 18
SP - 2571
EP - 2578
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 10
ER -