Prolonged Release Tacrolimus Has Comparable Safety and Efficacy Profile as Standard Release Tacrolimus in Heart Transplant Recipients

Abstract

Current data on safety and efficacy of prolonged release tacrolimus (PRT, Advagraf) in heart transplant (HTX) recipients is scarce. We sought to compare standard release tacrolimus (SRT) to PRT in this patient population. In a prospective cross-over single-center study we enrolled 70 HTX recipients transplanted between 2014 and 2017. In Phase 1 all patients received SRT and were followed for 6 months. Then SRT was switched for PRT (Phase 2) and the patients were followed for another 6 months. Target tacrolimus trough values for SRT and PRT in Phases 1 and 2 were 5-8 ng/mL. Renal dysfunction was defined as estimated glomerular filtration rate (eGFR)<90mL/min/1.73m2. Of 70 patients enrolled, 56 (80%) were male with the average age of 56±10 years, 40 (57%) had renal dysfunction, 16 (23%) had diabetes and 41 (59%) had hypertension. When comparing the two treatment strategies we found no differences regarding tacrolimus trough levels (7.1±1.4 ng/mL in SRT vs. 7.2±1.6 ng/mL in PRT, P=0.57) or cumulative drug dose (3.1±1.6 mg vs. 3.6±1.8 mg, P=0.11). Furthermore, we found no differences in eGFR (75±14 mL/min/1.73m2 in SRT vs. 73±18 mL/min/1.73m2 in PRT, P=0.69), Cystatin C levels (1.11±0.27 mg/dL vs. 1.08±0.33 mg/dL, P=0.68), glucose metabolism (HbA1c: 5.9±0.9% vs. 5.8±1.0%, P=0.68), allograft left ventricular ejection fraction (65±7% vs. 66±6%, P=0.84) or right ventricular function (TAPSE: 1.7±0.7 cm vs. 1.8±0.3 cm, P=0.39). Troponin levels (0.01±0.01 pg/mL in SRT vs. 0.01±0.02 pg/mL in PRT, P=0.29) and allograft rejection rates (0% in SRT vs. 1% in PRT, P=0.32) remained comparable. When stratifying patients according to the baseline eGFR no decline was observed in patients with either normal renal function (ΔeGFR -2.2±5.1 mL/min/1.73m2 in SRT vs. +0.6±5.6 mL/min/1.73m2 in PRT, P=0.19) or decreased renal function (ΔeGFR -0.9±7.7 mL/min/1.73m2 in SRT vs. -0.7±8.9 mL/min/1.73m2 in PRT, P=0.95). Prolonged-release tacrolimus may represent a safe and effective alternative to standard-release tacrolimus in heart transplant recipients.