Efficacy and safety of sirolimus and everolimus in heart transplant patients: a retrospective analysis

Background: Since its introduction as an immunosuppressant in the late 1990s, sirolimus (SRL) has been used to prevent rejections after heart transplantation (HTx) in the United States. An analogue, everolimus (ERL) has been mainly used in Europe. We performed a retrospective longitudinal single-center study to evaluate efficacy and side effects of SRL and ERL.

Patients and methods: We analyzed 71 patients, 39 in the SRL and 32 in the ERL group. The following data were collected: Trough levels of SRL and ERL, biopsy-proven rejections, renal function, blood lipids, hematology, blood pressure, pulse rate, and side effects (via an anonymous questionnaire). Follow-up time was 6 months. No prisoners or organs from prisoners were used in the study.

Results: Introduction of SRL or ERL into therapy took place 44 or 42 months (average) after HTx. SRL and ERL were equally effective in preventing rejection (8/39 versus 6/32). Hemoglobin levels decreased slightly in the SRL group (nonsignificant). Leucocytes and thrombocyte levels decreased in both groups (P < .05 only in the ERL group). Creatinine levels remained unchanged. Cholesterol and triglyceride levels increased significantly in the SRL group. High-density lipoprotein levels increased significantly in the ERL group. Vital signs remained stable in both groups. Side effects (mainly edema, gastrointestinal symptoms and infections) were considerable and prompted discontinuation in 39% of all patients in both groups. Infections were more frequent in SRL (18/39 versus 12/32, nonsignificant). Calcineurin therapy could be reduced by 25% in SRL and 45% in ERL.

Conclusion: The impact of SRL and ERL on laboratory values and rejection rates, as well as on clinical parameters, is similar with a slight advantage to ERL regarding lipids and rate of infections (not significant). Both SRL and ERL allow an important reduction of calcineurin-therapy; however, both drugs have considerable side effects, which often require discontinuation of therapy.