Tacrolimus time in therapeutic range and long‐term outcomes in heart transplant recipients

Abstract

Study Objective
Little is known about the association between tacrolimus time in therapeutic range (TTR) within the guideline‐recommended targets and heart transplant (HT) patient outcomes. This study evaluated the association of early tacrolimus TTR with rejection and other clinical outcomes during an extended follow‐up after HT.


Design
This was a single‐center retrospective cohort study.


Setting
The study was conducted at Michigan Medicine (1/1/2006–12/31/2017).


Patients
HT recipients ≥18 years of age were included.


Measurement
The primary end point was the effect of tacrolimus TTR on time to rejection over the entire follow‐up period.


Main Results

A total of 137 patients were included with a median follow‐up of 53 months. Based on the median TTR of 58%, the patients were divided into the low tacrolimus TTR (
n
 = 68) and high tacrolimus TTR (
n
 = 69) cohort. The high tacrolimus TTR was associated with a significantly lower risk of rejection compared to the low tacrolimus TTR cohort (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.41–0.98;
p
 = 0.04). A
post hoc
analysis revealed associations between rejection and TTR when high and low TTR groups were created at different levels. TTR <30% was associated with a 7‐fold higher risk of rejection (HR 7.56; 95% CI 1.76–37.6;
p
 < 0.01) and TTR >75% was associated with a 77% lower risk of rejection (HR 0.23; 95% CI 0.08–0.627;
p
 < 0.01).



Conclusions
Patients in the higher tacrolimus TTR cohort had a lower risk of rejection. We observed correlations between higher risk of rejection with TTR <30% and lower risk of rejection with TTR >75%. Future studies should focus on validating the optimal TTR cutoff while also exploring a cutoff to delineate high‐risk patients for which early interventions to improve tacrolimus TTR may be beneficial.