Impact of De Novo Everolimus-Based Immunosuppression on Incisional Complications in Heart Transplantation

Background. The mammalian target of rapamycin inhibitor sirolimus has been associated with an increased incidence of wound-healing complications after de novo heart transplantation. To evaluate the possibility of a similar association for everolimus, we performed a risk-factor analysis to compare the incidence of incision-related wound complications for everolimus with that of other adjunctive drugs. Methods. Safety data from 1009 heart transplant recipients (n = 214, receiving azathioprine; n = 84, mycophenolate mofetil (MMF); n = 711, everolimus) were reviewed in a post hoc analysis from three randomized, multicenter studies-B253 (n = 634), A2403 (n = 199), and A2411 (n = 176)-in which de novo patients received fixed-dose or concentration-controlled everolimus (target trough, 3-8 ng/mL), azathioprine, or MMF with standard-or reduced-exposure cyclosporine A. Incisional complications were analyzed for incidence, type, and severity up to day 90 posttransplant. Results. Incisional-complication events occurred in 25 (11.7%) azathioprine, six (7.2%) MMF, and 87 (12.3%) everolimus patients. Serious incisional complications were more frequent with everolimus (6.9%) compared with azathioprine (4.2%; P = 0.197) or MMF (1.2%; P = 0.051). In a univariate analysis, patient sex, body mass index (BMI), and diabetes were associated with incisional complications. Only BMI was significantly associated with incisional complications in the subsequent multivariate analysis, with the odds of an incisional-complication event increasing by 12.9% for every 1 kg/m(2) increase in BMI (P < 0.001). Conclusions. The incidence of incisional complications with everolimus was generally low, although numerically higher compared with MMF. Our analyses provided no strong evidence that everolimus is an independent risk factor for incisional complications. After de novo heart transplantation, patients with a high BMI are at higher risk of incision-related wound complications.