Long-Term Results of Calcineurin Inhibitor-Free Immunosuppression Using Everolimus after Heart Transplantation

Background: Immunosuppression is necessary after transplantation but it is associated with distinct adverse side effects. These negative effects could at least partially be overcome with the mammalian target of Rapamycin (mTOR) inhibitor everolimus. Few studies have examined everolimus therapy with calcineurin inhibitor (CNI) withdrawal in maintenance heart transplant patients (HTx).

Methods: In this prospective, single-arm, single-center study, maintenance patients after HTx were converted from CNI to everolimus. They were followed for 9.1 ± 4 years. Primary endpoints were kidney-function and arterial hypertension.

Results: Forty-eight patients were recruited (mean posttransplant time 5.4 ± 3.5 years) and followed up for 9.1 ± 4 years. Mean creatinine serum level decreased from 2.1 ± 0.6 at baseline to 1.6 ± 0.8 at month 48 and 1.7 ± 0.7 after 9.1 ± 4 years (p = not significant). Eight patients (16.6%) required dialysis. Median systolic and diastolic blood pressure, triglycerides, and low-density lipoprotein cholesterol, did not change significantly during the study period. Early resolution of most non-renal CNI-related adverse events was sustained. Due to rejection (1 pat.), pneumonitis (3 pat.), infection (2 pat.) and other side effects (8 pat.), CNI therapy had to be reintroduced in 14 patients (29.1%). No significant changes in cardiac function parameters were observed.

Conclusions: Calcineurin inhibitor-free immunosuppression with everolimus is an effective and safe option in selected maintenance HTx patients. Most adverse effects under everolimus occurred early after conversion and in most cases resolved without intervention within a few weeks. Refining selection criteria may help both in identifying patients who will profit most from switching and in alleviating the need to reintroduce CNI therapy.