title: Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients: a randomized trial.
abstract: In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3–6 ng/mL) with reduced-exposure cyclosporine (n = 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7–11 weeks and everolimus exposure increased (6–10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean ± SD: 79.8 ± 17.7 mL/min/1.73 m2 vs. 61.5 ± 19.6 mL/min/1.73 m2; p < 0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7–11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, p < 0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.
authors.forename: A K
authors.initials: AK
authors.lastname: Andreassen
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: F
authors.initials: F
authors.lastname: Gustafsson
authors.forename: H
authors.initials: H
authors.lastname: Eiskjaer
authors.forename: G
authors.initials: G
authors.lastname: Radegran
authors.forename: E
authors.initials: E
authors.lastname: Gude
authors.forename: K
authors.initials: K
authors.lastname: Jansson
authors.forename: D
authors.initials: D
authors.lastname: Solbu
authors.forename: V
authors.initials: V
authors.lastname: Sigurdardottir
authors.forename: S
authors.initials: S
authors.lastname: Arora
authors.forename: G
authors.initials: G
authors.lastname: Dellgren
authors.forename: L
authors.initials: L
authors.lastname: Gullestad
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000008:administration & dosage*; D016572:Cyclosporine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection; D006333:Heart Failure / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016277:Ventricular Function, Left
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D009173:Mycophenolic Acid; D020123:Sirolimus