Cardiovascular Parameters to 2 years After Kidney Transplantation Following Early Switch to Everolimus Without Calcineurin Inhibitor Therapy: An Analysis of the Randomized ELEVATE Study

BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors may confer cardioprotective advantages but clinical data are limited. METHODS: In the open-label ELEVATE trial, kidney transplant patients were randomized at 10–14 weeks posttransplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified endpoints included left ventricular mass index (LVMi) and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity (PWV). RESULTS: The mean change in LVMi from randomization was similar with everolimus versus CNI (month 24: -4.37 g/m versus -5.26 g/m; mean difference 0.89 [p=0.392]). At month 24, LVH was present in 41.7% versus 37.7% of everolimus and CNI patients, respectively. Mean PWV remained stable with both everolimus (mean change from randomization to month 12: -0.24 m/s; month 24: -0.03 m/s) or CNI (month 12: 0.11 m/s; month 24: 0.16 m/s). The change in mean ambulatory night time blood pressure from randomization showed a benefit for diastolic pressure at month 12 (p=0.039) but not month 24. Major adverse cardiac events occurred in 1.1% and 4.2% of everolimus-treated and CNI-treated patients, respectively by month 12 (p=0.018) and 2.3% (8/353) and 4.5% by month 24 (p=0.145). CONCLUSIONS: Overall, these data do not suggest a clinically relevant effect on cardiac endpoints following early conversion from CNI to a CNI-free everolimus-based regimen.