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Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Three-Year Results From the Randomized SCHEDULE Study
Oslo University Hospital, Norway.
Sahlgrens University Hospital, Sweden.
Rigshosp, Denmark.
Aarhus University Hospital, Denmark.
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2016 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 16, no 4, 1238-1247 p.Article in journal (Refereed) PublishedText
Abstract [en]

In a randomized, open-label trial, de novo heart transplant recipients were randomized to everolimus (3-6ng/mL) with reduced-exposure calcineurin inhibitor (CNI; cyclosporine) to weeks 7-11 after transplant, followed by increased everolimus exposure (target 6-10ng/mL) with cyclosporine withdrawal or standard-exposure cyclosporine. All patients received mycophenolate mofetil and corticosteroids. A total of 110 of 115 patients completed the 12-month study, and 102 attended a follow-up visit at month 36. Mean measured GFR (mGFR) at month 36 was 77.4mL/min (standard deviation [SD] 20.2mL/min) versus 59.2mL/min (SD 17.4mL/min) in the everolimus and CNI groups, respectively, a difference of 18.3mL/min (95% CI 11.1-25.6mL/min; p < 0.001) in the intention to treat population. Multivariate analysis showed treatment to be an independent determinant of mGFR at month 36. Coronary intravascular ultrasound at 36 months revealed significantly reduced progression of allograft vasculopathy in the everolimus group compared with the CNI group. Biopsy-proven acute rejection grade 2R occurred in 10.2% and 5.9% of everolimus- and CNI-treated patients, respectively, during months 12-36. Serious adverse events occurred in 37.3% and 19.6% of everolimus- and CNI-treated patients, respectively (p=0.078). These results suggest that early CNI withdrawal after heart transplantation supported by everolimus, mycophenolic acid and steroids with lymphocyte-depleting induction is safe at intermediate follow-up. This regimen, used selectively, may offer adequate immunosuppressive potency with a sustained renal advantage. A follow-up study of the SCHEDULE trial, which randomized de novo heart transplant recipients to everolimus with cyclosporine discontinuation or to standard-exposure cyclosporine, shows that measured glomerular filtration rate remains significantly higher in the everolimus group at three years posttransplant, with significantly reduced progression of allograft vasculopathy compared to cyclosporine therapy.

Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 16, no 4, 1238-1247 p.
Keyword [en]
clinical research; practice; heart transplantation; cardiology; immunosuppression; immune; immunosuppressant; mechanistic target of rapamycin: everolimus; immunosuppressant; mechanistic target of rapamycin (mTOR); clinical trial modulation
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-127413DOI: 10.1111/ajt.13588ISI: 000373075400024PubMedID: 26820618OAI: diva2:925583
Available from: 2016-05-02 Created: 2016-04-26 Last updated: 2016-05-02

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Jansson, Kjell
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Division of Cardiovascular MedicineFaculty of Health SciencesDepartment of Cardiology in Linköping
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