title: The Effect of Everolimus Initiation and Calcineurin Inhibitor Elimination on Cardiac Allograft Vasculopathy in De Novo Recipients: One-Year Results of a Scandinavian Randomized Trial.
abstract: Early initiation of everolimus with calcineurin inhibitor therapy has been shown to reduce the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients. The effect of de novo everolimus therapy and early total elimination of calcineurin inhibitor therapy has, however, not been investigated and is relevant given the morbidity and lack of efficacy of current protocols in preventing CAV. This 12-month multicenter Scandinavian trial randomized 115 de novo heart transplant recipients to everolimus with complete calcineurin inhibitor elimination 7-11 weeks after HTx or standard cyclosporine immunosuppression. Ninety-five (83%) patients had matched intravascular ultrasound examinations at baseline and 12 months. Mean (± SD) recipient age was 49.9 ± 13.1 years. The everolimus group (n = 47) demonstrated significantly reduced CAV progression as compared to the calcineurin inhibitor group (n = 48) (ΔMaximal Intimal Thickness 0.03 ± 0.06 and 0.08 ± 0.12 mm, ΔPercent Atheroma Volume 1.3 ± 2.3 and 4.2 ± 5.0%, ΔTotal Atheroma Volume 1.1 ± 19.2 mm(3) and 13.8 ± 28.0 mm(3) [all p-values ≤ 0.01]). Everolimus patients also had a significantly greater decline in levels of soluble tumor necrosis factor receptor-1 as compared to the calcineurin inhibitor group (p = 0.02). These preliminary results suggest that an everolimus-based CNI-free can potentially be considered in suitable de novo HTx recipients.
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Arora
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: A K
authors.initials: AK
authors.lastname: Andreassen
authors.affiliation: Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Gustafsson
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Eiskjaer
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Denmark.
authors.forename: H E
authors.initials: HE
authors.lastname: Bøtker
authors.affiliation: The Clinic for Heart Failure and Valvular Disease, Skåne University Hospital and Lund University, Lund, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Rådegran
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Gude
authors.affiliation: Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Ioanes
authors.affiliation: Novartis Norge AS, Oslo, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Solbu
authors.affiliation: Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Sigurdardottir
authors.affiliation: Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Dellgren
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Erikstad
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: O G
authors.initials: OG
authors.lastname: Solberg
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammatory Research Center, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Research Institute for Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammatory Research Center, Faculty of Medicine, University of Oslo, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.|K.G. Jebsen Cardiac Research Center and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D000328:Adult; D064591:Allografts; D065095:Calcineurin Inhibitors / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D006085:Graft Survival; D006331:Heart Diseases / Q000150:complications / Q000601:surgery*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D020123:Sirolimus / Q000627:therapeutic use; D066027:Transplant Recipients; D014652:Vascular Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus
keywords: clinical research / practice; heart (allograft) function / dysfunction; heart transplantation / cardiology; immunosuppressant; mechanistic target of rapamycin: everolimus