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.
Arora S, Andreassen AK, et al.American Journal of Transplantation. 2015 Jul; 15(7): 1967-75
Aims
This sub-study of the SCHEDULE trial evaluates the effect of everolimus and cyclosporine (CsA) elimination on cardiac allograft vasculopathy (CAV) in de novo heart transplant recipients.
Interventions
(i) low-dose everolimus, low-dose CsA, mycophenolate mofetil (MMF) and corticosteroids with withdrawal of CsA and step up to everolimus full dose after 7–11 weeks or (ii) conventional treatment with CsA, MMF and corticosteroids. The first dose of everolimus, CsA, MMF and corticosteroids was administered no later than the fifth postoperative day.
Participants
97 of 115 de novo heart transplant patients in the SCHEDULE trial. 47 patients received Everolimus and 49 patients received CsA.
Outcomes
The primary endpoint was intravascular ultra sound analysis of CAV progression (i.e. increase in maximal intimal thickness. Secondary outcomes included incidence of CAV and normalized total atheroma volume. Parallel assessment of a range of inflammatory markers was also performed.
Follow-up
12 months
CET Conclusions
This pre-planned sub-analysis of the SCHEDULE trial investigates the effects of complete CNI withdrawal and conversion to everolimus shortly after liver transplantation on cardiac allograft vasculopathy (CAV), as measured by intravenous ultrasound. There is a significant reduction in parameters of CAV in the everolimus cohort at 12 months, despite a higher incidence of acute rejection in this arm. The authors conclude that conversion to everolimus is likely safe, with potential benefits in terms of renal function and CAV. There are limitations. The patient cohort is fairly homogenous, and findings may not generalise to other settings. The gold-standard for measurement of CAV is angiography, and the clinical significance of the IVUS parameters reported here is uncertain. Longer follow-up would be required to see if these changes translate to improved graft survival, especially in the context of a significantly higher acute rejection rate.
Data analysis
Available case analysis
Quality notes
Previously reported: Andreassen A, Andersson B, Gustaffson F, et al. Everolimus initiation and early calcineurin inhibitor withdrawal in heart transplant recipients: A randomized trial. Am J Transplant 2014; 14: 1828–1838.
Trial registration
NCT01266148