ABSTRACT
BACKGROUND: Everolimus is an immunosuppressive agent that reduces cardiac allograft vasculopathy. This report presents the 24-month results of a multicenter trial of everolimus vs azathioprine in heart transplantation. METHODS: A total of 634 patients were randomized to receive 1.5 mg everolimus, 3 mg everolimus or azathioprine, with cyclosporine and steroids. A 12-month, double-blind, double-dummy period was followed by a 12-month open-label period. RESULTS: At 24 months, the percentage of patients reaching the composite efficacy end-points was significantly lower with everolimus (1.5 mg: 45.9%, p = 0.016; 3 mg: 36.0%, p < 0.001) than with azathioprine (57.5%). The change in maximal intimal thickness from baseline to 24 months was significantly smaller with everolimus 1.5 mg (0.07 mm, p = 0.014) and 3 mg (0.06 mm, p = 0.004) compared with azathioprine (0.15 mm). The 24-month incidence of vasculopathy was 33.3% with everolimus 1.5 mg, 45.5% with everolimus 3 mg and 58.3% with azathioprine (p = 0.017 vs everolimus 1.5 mg). Incidence of cytomegalovirus infection was 3-fold lower in patients receiving everolimus compared with azathioprine (7.2% and 7.1% in the 1.5-mg and 3-mg everolimus cohorts, respectively, and 21% in the azathioprine group; p < 0.0001). Median serum creatinine levels at 24 months were higher with everolimus than with azathioprine, but decreased when cyclosporine exposure was reduced (everolimus 1.5 mg: baseline 167 micromol, after 6 months 157.5 micromol; everolimus 3 mg: baseline 185.6 micromol, after 6 months 160 micromol; azathioprine: baseline 123.3 micromol, after 6 months 127 micromol). CONCLUSIONS: Everolimus significantly reduced acute rejection and limited the progression of allograft vasculopathy at 24 months compared with azathioprine. Although graft and patient survival was comparable at 24 months, everolimus therapy may improve longer-term outcomes after heart transplantation.
Subject(s)
Graft Rejection/prevention & control , Heart Transplantation/immunology , Immunosuppressive Agents/therapeutic use , Sirolimus/analogs & derivatives , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Azathioprine/therapeutic use , Cyclosporine/therapeutic use , Double-Blind Method , Everolimus , Graft Rejection/epidemiology , Graft Rejection/pathology , Heart Transplantation/pathology , Humans , Kidney Function Tests , Middle Aged , Safety , Sirolimus/therapeutic use , Transplantation, Homologous/pathology , Treatment OutcomeABSTRACT
En este artículo se comentan las principales novedades que han surgido en el último año en el ámbito de la insuficiencia cardíaca (IC). Se incluyen los avances en el diagnóstico y el tratamiento médico de la IC, el trasplante cardíaco, la cirugía de remodelado ventricular, los dispositivos de asistencia mecánica circulatoria, la resincronización cardíaca y la terapia celular. Se pone de manifiesto que el manejo actual de la IC es un gran reto que depende en gran medida del avance de la investigación a diferentes niveles y de las modificaciones subsiguientes en la práctica clínica para incorporar esos avances (AU)
In this article the most recent advances in the field of heart failure over the last year are presented. These include advances in the diagnosis and medical treatment of heart failure, heart transplantation, left ventricular reconstruction surgery, mechanical assist devices, cardiac resynchronization and cell therapy. Nowadays, heart failure management is a big challenge because it depends on on-going multi-disciplinary investigation and subsequent changes in clinical practice in order to implement such advances (AU)
