title: Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial.
abstract: The NOCTET study randomized 282 patients ≥1 year after heart or lung transplantation to continue conventional calcineurin inhibitor (CNI) therapy or to start everolimus with reduced-exposure CNI. Last follow-up, at ≥5 years postrandomization (mean: 5.6 years) was attended by 72/140 everolimus patients (51.4%) and 91/142 controls (64.1%). Mean measured GFR remained stable in the everolimus group from randomization (51.3 ml/min) to last visit (51.4 ml/min) but decreased in controls (from 50.5 ml/min to 45.3 ml/min) and was significantly higher with everolimus at last follow-up (P = 0.004). The least squares mean (SE) change from randomization was -1.5 (1.7)ml/min with everolimus versus -7.2 (1.7)ml/min for controls (difference: 5.7 [95% CI 1.7; 9.6]ml/min; P = 0.006). The difference was accounted for by heart transplant patients (difference: 6.9 [95% 2.3; 11.5]ml/min; P = 0.004). Lung transplant patients showed no between-group difference at last follow-up. Rates of rejection, death, and major cardiac events were similar between groups, as was graft function. Pneumonia was more frequent with everolimus (18.3% vs. 6.4%). In conclusion, introducing everolimus in maintenance heart transplant patients, with reduced CNI, achieves a significant improvement in renal function which is maintained for at least 5 years, but an early renal benefit in lung transplant patients was lost. Long-term immunosuppressive efficacy was maintained.
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Gullestad
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Eiskjaer
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Finn
authors.initials: F
authors.lastname: Gustafsson
authors.affiliation: Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Gerdt C
authors.initials: GC
authors.lastname: Riise
authors.affiliation: Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Kristjan
authors.initials: K
authors.lastname: Karason
authors.affiliation: Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Dellgren
authors.affiliation: Department of Clinical Sciences Lund, Cardiology, Lund University and the Section for Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Rådegran
authors.affiliation: Department of Respiratory Medicine, Lund University Hospital and Skåne University Hospital, Lund, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hansson
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Faculty of Medicine, K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Einar
authors.initials: E
authors.lastname: Gude
authors.affiliation: Department of Respiratory Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bjørtuft
authors.affiliation: Department of Cardiology, Heart Center, University Hospital, Linkoping, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Jansson
authors.affiliation: Division of Lung Transplantation, Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Schultz
authors.affiliation: Novartis Norge AS, Oslo, Norway.
authors.forename: Dag
authors.initials: D
authors.lastname: Solbu
authors.affiliation: Division of Lung Transplantation, Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D003718:Denmark; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006085:Graft Survival; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016040:Lung Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009664:Norway; D011014:Pneumonia / Q000209:etiology; D013548:Sweden; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus
keywords: calcineurin inhibitor; certican; cyclosporine; everolimus; heart; lung; randomized; renal impairment; tacrolimus; transplantation