Five-Year Results of Everolimus-Based Immunosuppression with and without Calcineurin Inhibitors after Heart Transplantation

Objectives: Clinical study results are still controversial about the timing of starting Everolimus (ERL) with and without calcineurin inhibitors (CNIs) after heart transplantation (HTx). We analyzed long-term data of the effect of ERL on renal function, the incidence of biopsy-proven acute cellular rejection (BPACR), and the incidence of cardiac allograft vasculopathy (CAV) in a real-life scenario.

Methods: A total of 105 patients received HTx between 2005 and 2015, and were divided into three groups (Gs) according to time of ERL start: G1: ERL start ≤3 months after HTx (n = 46), G2: ERL start 4 to 12 months after HTx (n = 33), and G3: ERL start >12 months after HTx (n = 26). Additionally, we analyzed patients either with early CNI withdrawal ≤3 months (SG1, n = 25) after ERL start or with concomitant CNI therapy > 12 months (SG2, n = 71) after ERL start. Renal function was calculated using MDRD formula for glomerular filtration rate (GFR) in relation to baseline value before ERL admission, and at 12 and 60 months after ERL start (ΔGFR mL/min). CAV was assessed with coronary angiography for all patients. Incidence of BPACR (≥2R) was compared between the study groups at 12 and 60 months after HTx.

Result: At 12 months after ERL start, GFR was significantly higher in G2 as compared with G3 (ΔGFR: G2: +3.98 mL/min vs. G3: −4.98 mL/min, p = 0.04). Furthermore, early CNI withdrawal did not further improve renal function at 12 months. However, G1 had a higher ΔGFR at 60 months after ERL start compared to G2 and G3 (G1: +1.59 mL/min, G2: −12.71 mL/min, G3: −6.26 mL/min, p1 vs. p2 = 0.035 and p1 vs. p3 = 0.27). In all three groups, early CNI withdrawal leads to a higher GFR compared with concomitant CNI therapy at 60 months after HTx. Incidence of BPACR at 12 months after HTx showed no differences between the groups (G1: 15.2%, G2: 19.1%, G3: 19.2%, p = 0.72). However, CNI-free patients of G1 had a higher incidence of BPACR than patients with concomitant CNI therapy of G1 at 12 months (SG1: 33.3% vs. SG2: 6.9%, p = 0.03) and at 60 months (SG1: 22% vs. SG2: 0%, p = 0.049). All BPACR were without hemodynamic compromise. Regarding CAV, no significant difference was seen at 60 months (G1: 11.8%, G2: 5.6%, G3: 8%, p = 0.74).

Conclusion: Early ERL therapy within 3 months of HTx had a long-term beneficial effect on renal function. Early CNI withdrawal further enhanced the nephroprotective effect. While the incidence of BPACR was increased by early CNI-withdrawal, echocardiographic assessed graft function, however, was not impaired. The incidence of CAV was not different among the study groups.

No conflict of interest has been declared by the author(s).

Publication History

Article published online:
19 February 2021