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

Abstract

Background. Mammalian target of rapamycin inhibitors may confer cardioprotective advantages, but clinical data are limited. Methods. In the open-label ELEVATE trial, kidney transplant patients were randomized at 10 to 14 weeks after transplant to convert from calcineurin inhibitor (CNI) to everolimus or remain on standard CNI therapy. Prespecified end points included left ventricular mass index and, in a subpopulation of patients, arterial stiffness as measured by pulse wave velocity. Results. The mean change in left ventricular mass index from randomization was similar with everolimus versus CNI (month 24, -4.37 g/m(2.7) versus -5.26 g/m(2.7); mean difference, 0.89 [p = 0.392]). Atmonth 24, left ventricular hypertrophy was present in 41.7% versus 37.7% of everolimus and CNI patients, respectively. Mean pulse wave velocity remained stable with both everolimus (mean change from randomization to month 12, -0.24 m/s; month 24, -0.03m/s) and CNI (month 12, 0.11 m/s; month 24, 0.16 m/s). The change in mean ambulatory nighttime blood pressure from randomization showed a benefit for diastolic pressure at month 12 (P = 0.039) but not at 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 end points after early conversion from CNI to a CNI-free everolimus-based regimen.