title: Calcineurin inhibitor-free immunosuppression using everolimus (Certican) after heart transplantation: 2 years' follow-up from the University Hospital Münster.
abstract: BACKGROUND
  Everolimus is a proliferation-signal inhibitor which was introduced for heart transplant recipients in 2004. To date, there are only sparse data about long-term calcineurin inhibitor (CNI)-free immunosuppression using everolimus.
  
  
  METHODS
  After heart transplantation, patients receiving everolimus were consecutively enrolled. Reasons for switching to everolimus were side effects of CNI immunosuppression, such as deterioration of kidney function and recurrent rejection episodes. All 60 patients underwent standardized switching protocols, 42 patients completed 24-month follow-up. Blood was sampled for lipid status, renal function, routine controls, and levels of immunosuppressive agents. On days 0, 14, and 28, and then every 3 months, echocardiography and physical examination were performed.
  
  
  RESULTS
  After switching to everolimus, most patients recovered from the side effects. Renal function improved significantly after 24 months (creatinine, 2.1 ± 0.6 vs 1.8 ± 1 mg/dL; P < .001; creatinine clearance, 41.8 ± 22 vs 48.6 ± 21.8 mL/min; P < .001). Median blood pressure increased from 120.0/75.0 mm Hg at baseline to 123.8/80.0 mm Hg at month 24 (P values .008 and .003 for systolic and diastolic pressures, respectively). Tremor, peripheral edema, hirsutism, and gingival hyperplasia markedly improved. Levels of interleukin-6 were stable between baseline and 24-month levels. Temporary adverse events occurred in 8 patients [13.3%: interstitial pneumonia (n = 2), skin disorders (n = 2); reactivated hepatitis B (n = 1), and fever of unknown origin (n = 3)].
  
  
  CONCLUSIONS
  CNI-free immunosuppression using everolimus is safe, with excellent efficacy in maintenance of heart transplant recipients. Arterial hypertension and renal function significantly improved. CNI-induced side effects, such as tremor, peripheral edema, hirsutism, and gingival hyperplasia, markedly improved in most patients.
authors.affiliation: Department of Cardiology and Angiology, University Hospital Münster, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Stypmann
authors.forename: M A
authors.initials: MA
authors.lastname: Engelen
authors.forename: S
authors.initials: S
authors.lastname: Eckernkemper
authors.forename: S
authors.initials: S
authors.lastname: Amler
authors.forename: S
authors.initials: S
authors.lastname: Gunia
authors.forename: J R
authors.initials: JR
authors.lastname: Sindermann
authors.forename: M
authors.initials: M
authors.lastname: Rothenburger
authors.forename: A
authors.initials: A
authors.lastname: Rukosujew
authors.forename: G
authors.initials: G
authors.lastname: Drees
authors.forename: H A
authors.initials: HA
authors.lastname: Welp
mesh_terms: D000368:Aged; D001794:Blood Pressure; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood / Q000652:urine; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D016027:Heart Transplantation; D006785:Hospitals, University; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D003404:Creatinine; D020123:Sirolimus