Wound complications and surgical events in de novo heart transplant patients treated with everolimus: Post-hoc analysis of the SCHEDULE trial

OBJECTIVES: The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx) everolimus (EVE) de novo trial with early calcineurin (CNI) avoidance (SCHEDULE). The aim of the study was to compare wound complications between EVE and CNI based regimen.

MATERIALS AND METHODS: A total of 115 patients (mean age 51 ± 13 years, 73% men) were randomized within five days post-HTx to low dose EVE and reduced dose Cyclosporine (CyA) followed by early CyA withdrawal (EVE group; n=56) or standard CyA regimen (CyA group; n=59). All AE/SAEs were prospectively recorded according to the SCHEDULE study protocol, and re-assessed retrospectively by two independent reviewers. Wound complication as primary endpoint was defined as any complication associated with failure of tissue healing. Secondary endpoint was total number of events involving surgical intervention.

RESULTS: There were no significant differences between the groups with regards to wound complications (EVE=20, CyA=12)(p=0.08) or total surgical events (EVE=38, CyA=34) (p=0.44). Age>54.5 years (median) was an overall risk factor for surgical wound complications regardless of treatment group (p=0.025). There was no difference in the EVE versus CyA group with regards to other surgical events. Majority of events were in 1/3 of the patients.

CONCLUSION: De novo initiation of EVE and early CyA withdrawal in HTx patients did not show any significant differences in wound complications or in total surgical events. Majority of complications were seen in a small number of patients.