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Transpl Int. 2016 Jul;29(7):819-29. doi: 10.1111/tri.12783. Epub 2016 May 30.

Long-term outcomes of thoracic transplant recipients following conversion to everolimus with reduced calcineurin inhibitor in a multicenter, open-label, randomized trial.

Author information

1
Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
2
Faculty of Medicine, K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
3
Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
4
Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
5
Department of Respiratory Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
6
Department of Cardiology and Transplant Institute, Sahlgrenska University Hospital, Gothenburg, Sweden.
7
Department of Clinical Sciences Lund, Cardiology, Lund University and the Section for Heart Failure and Valvular Disease, Skåne University Hospital, Lund, Sweden.
8
Department of Respiratory Medicine, Lund University Hospital and Skåne University Hospital, Lund, Sweden.
9
Department of Respiratory Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
10
Department of Cardiology, Heart Center, University Hospital, Linkoping, Sweden.
11
Division of Lung Transplantation, Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
12
Novartis Norge AS, Oslo, Norway.

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.

KEYWORDS:

calcineurin inhibitor; certican; cyclosporine; everolimus; heart; lung; randomized; renal impairment; tacrolimus; transplantation

PMID:
27067532
DOI:
10.1111/tri.12783
[Indexed for MEDLINE]
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