title: Prospective study of everolimus with calcineurin inhibitor-free immunosuppression after heart transplantation: results at four years.
abstract: BACKGROUND
  Immunosuppression is necessary after transplantation but it is associated with distinct adverse side effects. These negative effects could at least partially be overcome with the mammalian target of Rapamycin (mTOR) inhibitor everolimus. Few studies have examined everolimus therapy with calcineurin inhibitor (CNI) withdrawal in maintenance heart transplant patients (HTx).
  
  
  METHODS
  In this prospective, single-arm, single-center study, maintenance patients after HTx were converted from CNI to everolimus. They were followed for 48 months. Primary endpoints were kidney-function and arterial hypertension.
  
  
  RESULTS
  Forty-eight patients were recruited (mean post-transplant time 5.4 ± 3.5 years). Of these, 36 were followed for the entire 4-year period. Median calculated glomerular filtration rate increased from 40.7 (32.4 to 59.1) mL/minute at baseline to 48.9 (29.7 to 67)) mL/minute at month 48 (p = not significant). Median systolic and diastolic blood pressure, triglycerides, and high-density lipoprotein and low-density lipoprotein cholesterol, did not change significantly in a comparison of the values at baseline and at 48 months. Early resolution of most non-renal CNI-related adverse events was sustained. Due to adverse events, CNI therapy had to be reintroduced in 6 patients (12.5%). No significant changes in cardiac function parameters were observed.
  
  
  CONCLUSIONS
  Calcineurin inhibitor-free immunosuppression with everolimus is an effective and safe option in selected maintenance HTx patients. Most adverse effects under everolimus occurred early after conversion and in most cases resolved without intervention within a few weeks. Refining selection criteria may help both in identifying patients who will profit most from switching and in alleviating the need to reintroduce CNI therapy.
authors.affiliation: Department of Cardiovascular Medicine, Division of Cardiology, University of Muenster, Muenster, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Engelen
authors.affiliation: Department of Cardiac Surgery, University of Muenster, Muenster, Germany. Electronic address: henryk.welp@ukmuenster.de.
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Welp
authors.affiliation: Department of Cardiovascular Medicine, Division of Cardiology, University of Muenster, Muenster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gunia
authors.affiliation: Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Amler
authors.affiliation: Department of Cardiovascular Medicine, Division of Cardiology, University of Muenster, Muenster, Germany.
authors.forename: Mortimer Phil
authors.initials: MP
authors.lastname: Klarner
authors.affiliation: Department of Cardiac Surgery, University of Muenster, Muenster, Germany.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Dell'aquila
authors.affiliation: Department of Cardiovascular Medicine, Division of Cardiology, University of Muenster, Muenster, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Stypmann
mesh_terms: D000328:Adult; D000368:Aged; D019703:Calcineurin / Q000009:adverse effects; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068338:Everolimus; D019703:Calcineurin; D020123:Sirolimus