Everolimus is associated with a reduced incidence of cytomegalovirus infection following de novo cardiac transplantation.
Kobashigawa J, Ross H, et al.Transplant Infectious Disease 15(2): 150-162.
Aims
To investigate the efficacy and safety of everolimus in heart transplant recipients by analysing the cytomegalovirus (CMV) outcomes for the overall treatment groups and subgroups of patients from three randomised controlled trials.
Interventions
In study 1 patient received fixed dose everolimus or azathriopine (AZA) together with standard dose cyclosporine microemulsion (CsA-ME)and corticosteroids. In study 2, patients received everolimus with either full dose or reduced dose CsA-ME and corticosteroids. In study 3 patients received everolimus with reduced dose CsA-ME and corticosteroids or mycophenolate mofetil together with standard dose CsA-ME.
Participants
1009 patients undergoing heart transplantation.
Outcomes
The outcomes included occurrence of CMV infection as reported by the investigators and combined occurrence of CMV syndrome/disease.
Follow-up
Not reported.
CET Conclusions
This paper reports a post-hoc analysis of the patterns of CMV rejection in three trials investigating the use of everolimus in cardiac transplant recipients. The authors demonstrate a lower incidence of CMV infection in the everolimus-treated arms of these trials when compared to either azathioprine or MMF, irrespective of recipient CMV status or use of prophylaxis. It should, however, be noted that the original trials demonstrated inferior renal function in the everolimus-treated patients with higher adverse event rates in some trials, and that everolimus was being used in conjunction with cyclosporine in all trials. The clinical efficacy and safety of a combination of everolimus and tacrolimus (now more commonly in use) is less certain, and there is clearly a trade-off between the risk of CMV infection and other safety outcomes with the use of everolimus.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov NCT00098007 and NCT00150046