title: Wound complications and surgical events in de novo heart transplant patients treated with everolimus: Post-hoc analysis of the SCHEDULE trial.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway; Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway. Electronic address: mitrarashidi@hotmail.com.
authors.forename: Mitra
authors.initials: M
authors.lastname: Rashidi
authors.affiliation: Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Sorosh
authors.initials: S
authors.lastname: Esmaily
authors.affiliation: Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: Arnt E
authors.initials: AE
authors.lastname: Fiane
authors.affiliation: Department of Cardiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Gude
authors.affiliation: Department of Plastic and Reconstructive Surgery, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Norway.
authors.forename: Kim
authors.initials: K
authors.lastname: A Tønseth
authors.affiliation: Faculty of Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Norway.
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Finn
authors.initials: F
authors.lastname: Gustafsson
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Eiskjær
authors.affiliation: The Clinic for Heart Failure and Valvular Disease, Skåne University Hospital and Department of Clinical Sciences Lund, Cardiology, Lund University, Lund, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Rådegran
authors.affiliation: Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Dellgren
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects* / Q000639:trends; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D013530:Surgical Wound Infection / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus
keywords: Heart transplantation; Randomized study; Surgical events; Wound infection