Purpose: Everolimus is a proliferation signal inhibitor which has 2004 been introduced for
heart transplant recipients. To date, there is only sparse data about long term calcineurin
inhibitor (CNI)-free immunosuppression using everolimus.
Methods: Patients after HTx receiving everolimus were enrolled over a period of 9 months.
Reasons for switching to everolimus were side effects of CNI immunosuppression, such
as deterioration of kidney function and recurrent rejection episodes. All 60 patients
underwent standardized switching protocols, 42 patients completed 24-months follow-up.
Blood was sampled for lipid status, renal function, routine controls, and levels of
immunosuppressive agents. On days 0, 14, 28, and thereafter every 3 months, echocardiography
and physical examination were performed.
Results: After switching to everolimus, most patients recovered from the side effects. Renal
function improved significantly after 24 months (creatinine: 2.1±0.6 vs. 1.8±1mg/dL,
P<0.001; creatinine clearance: 41.8±22 vs. 48.6±21.8 mL/min, P<0.001). Arterial
hypertension significantly improved after 3 months and remained decreased over the
observation period (P<0.001 for systolic and diastolic blood pressure). Tremor,
peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Levels of
interleukin 6 where stable when comparing baseline and 24 month. Temporary adverse
events occurred in eight patients [13.3%; interstitial pneumonia (n=2); skin disorders
(n=2); reactivated hepatitis B (n=1); fever of unknown origin (n=3)].
Conclusion: CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance
heart transplant recipients. Arterial hypertension and renal function significantly
improved. CNI-induced side effects such as tremor, peripheral edema, hirsutism, and
gingival hyperplasia markedly improved in most patients.
