title: Calcineurin inhibitor-free immunosuppression using everolimus (Certican) in maintenance heart transplant recipients: 6 months' follow-up.
abstract: BACKGROUND
  Everolimus is a proliferation signal-inhibitor recently introduced in heart transplant recipients. To date, little is known about calcineurin inhibitor (CNI)-free immunosuppression using everolimus. This study reports the results of CNI-free immunosuppression using everolimus.
  
  
  METHODS
  During a continuous 9-month period, 60 heart transplant recipients were enrolled. Reasons for switching to everolimus were side effects associated with prior CNI immunosuppression. All patients underwent standardized switching protocols and completed 6 months of follow-up. Blood was obtained for lipid status, renal function, routine controls, and levels of immunosuppressive agents. Echocardiography and a physical examination were performed on Days 0, 14, 28, and then every 3 months.
  
  
  RESULTS
  After switching to everolimus, most patients recovered from the side effects associated with CNIs. Renal function improved significantly after 6 months (creatinine, 2.1 +/- 0.6 vs 1.5 +/- 0.9 mg/dl, p = 0.001; creatinine clearance, 42.2 +/- 21.6 vs 61.8 +/- 23.4 ml/[min x 1.73 m2], p = 0.018). Arterial hypertension improved after 3 months and remained decreased during the observation period. Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Adverse events occurred in 8 patients (13.3%), including interstitial pneumonia (n = 2), skin disorders (n = 2), reactivated hepatitis B (n = 1), and fever of unknown origin (n = 3).
  
  
  CONCLUSIONS
  Preliminary data suggest that CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance heart transplant recipients. Arterial hypertension and renal function improved significantly. CNI-induced side effects such as tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved in most patients.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Muenster, Berlin, Germany. markus.rothenburger@novartis.com
authors.forename: Markus
authors.initials: M
authors.lastname: Rothenburger
authors.forename: Elisa
authors.initials: E
authors.lastname: Teerling
authors.forename: Christian
authors.initials: C
authors.lastname: Bruch
authors.forename: Hans
authors.initials: H
authors.lastname: Lehmkuhl
authors.forename: Barbara
authors.initials: B
authors.lastname: Suwelack
authors.forename: Christoph
authors.initials: C
authors.lastname: Bara
authors.forename: Thomas
authors.initials: T
authors.lastname: Wichter
authors.forename: Frank
authors.initials: F
authors.lastname: Hinder
authors.forename: Christof
authors.initials: C
authors.lastname: Schmid
authors.forename: Joerg
authors.initials: J
authors.lastname: Stypmann
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D000068338:Everolimus; D005260:Female; D005335:Fever of Unknown Origin / Q000139:chemically induced; D005500:Follow-Up Studies; D016027:Heart Transplantation; D006515:Hepatitis B virus / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D017563:Lung Diseases, Interstitial / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012871:Skin Diseases / Q000139:chemically induced; D013997:Time Factors; D014775:Virus Activation
chemical_list: D007166:Immunosuppressive Agents; D008055:Lipids; D000068338:Everolimus; D020123:Sirolimus