Calcineurin inhibitor-free immunosupression using everolimus (certican) after heart transplantation: 2 years' follow up

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.