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

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.