Mid-Term Effectiveness of Everolimus on Heart Transplant Recipients with Renal Dysfunction or Transplant Coronary Artery Atherosclerosis

Abstract

Everolimus (EVL) can be utilized after heart reduce calcineurin inhibitor (CNI) associated nephrotoxicity, due to cell cycle inhibitor adverse effects, and as adjunct therapy for rejection and cardiac allograft vasculopathy (TCAV). Since 2007, we have primarily considered converting from mycophenolate mofetil with standard-dose CNIs to EVL with low-dose CNIs for the following recipients: 1) recipients with impaired renal function; 2) those with increases in or an initially large maximal intimal thickness (MIT) on routine intravascular ultrasound (IVUS) examinations; 3) donor derived TCAV; and 4) those with MMF-related leukopenia. In the present study, mid-term safety and effectiveness of EVL on heart transplant recipients with renal dysfunction or TCAV. A single-center, retrospective cohort study was conducted including 116 adult heart transplant patients between 1999 and 2018. Sixty nine of 116 patients was started EVL and patients who was initiated EVL due to renal dysfunction (n=21) with longer than 1 year follow-up of serum creatine and TCAV (n=22) with longer than 3 years follow-up of annual MIT measurement by IVUS were enrolled in this study. The trough levels of EVL were evaluated at 1 week after initiation. Once target trough levels of EVL (6-8 ng/mL) were achieved, the CNI dose was reduced to obtain target trough levels. EVL efficacy on renal dysfunction and TCAV and safety were assessed. In 21 patients given EVL due to renal dysfunction, serum creatinine was significantly decreased from initiation of EVL to 1 year after initiation (1.44 +/- 0.32 vs 1.23 +/- 0.36 mg/dL; p=0.0004), but that did not significantly changed since then. In 22 patients given EVL due to TCAV, MIT was significantly decreased from initiation of EVL to 3 years after initiation (1.20 +/- 0.38 mm vs 1.00 +/- 0.40 mm, p<0.001), but that did not significantly changed since then. EVL with low-dose CNI might play a role in short-term improvement in renal function and TCAV in heart transplant patients. However, immunosuppressive regimen to furtherly improve renal function or TCAV mid-term after initiation of EVL should be investigated.