A lower incidence of cytomegalovirus infection in de novo heart transplant recipients randomized to everolimus.
BACKGROUND
Cytomegalovirus (CMV) infection in recipients of cardiac transplants is associated with higher rates of morbidity. A recent phase III trial showed highly significantly (P<0.001) lower CMV rates with the proliferation signal inhibitor everolimus compared to azathioprine (AZA). To better define this association, data on CMV risk factors were collected retrospectively and analyzed.


METHODS
Data on CMV risk factors from a multicenter phase III trial on de novo heart transplant recipients (n=634) receiving a triple immunosuppressive regimen randomized to everolimus 1.5 mg/day (group 1), everolimus 3 mg/day (group 2), or AZA (group 3) were merged with prospectively collected CMV-related outcome data and analyzed.


RESULTS
CMV-positive donors (D+) and CMV-negative recipients (R-) were evenly distributed across groups 1-3 at 36/209 (17.2%), 48/211 (22.7%), and 38/214 (17.8%), respectively. CMV prophylaxis had been given for a mean (SD) of 175 (127.8), 183 (137.1), and 177 (132.9) days, respectively. In the high-risk D+/R- subgroup with prophylaxis, the proportions of patients with CMV infection compared with group 3 (12/29 [41.4%]) were 3/25 (12.0%) in group 1 (P=0.031) and 6/36 (16.7%) in group 2 (P=0.049). In D+/R+ subgroups either with or without prophylaxis, the everolimus groups had less CMV disease (P<0.001). The incidence of CMV syndrome, organ involvement, and laboratory evidence was lower with everolimus use compared to AZA.


CONCLUSIONS
Everolimus is associated with lower rates of CMV infection, syndrome, or organ involvement, suggesting an additional advantage from the use of everolimus in cardiac transplant recipients.
Hill
James A
JA
Medical Director Heart Failure/Transplantation, Shands Hospital at the University of Florida, Gainesville, FL, USA. hillja@medicine.ufl.edu
Hummel
Manfred
M
Starling
Randall C
RC
Kobashigawa
Jon A
JA
Perrone
Sergio V
SV
Arizón
Josè M
JM
Simonsen
Svein
S
Abeywickrama
Kamal H
KH
Bara
Christoph
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000187:drug effects* / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D000068338:Everolimus; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014019:Tissue Donors
D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus