Key result
Switching from cyclosporine A to everolimus stabilized pulse wave velocity (change -0.37 m/s, P=0.16), whereas continued cyclosporine A led to a significant increase (change 0.89 m/s, P=0.03).
Why the study?
Does switching from cyclosporine A to everolimus improve pulse wave velocity in stable de-novo renal allograft recipients?
RCT (n=27)
randomized
Does switching from cyclosporine A to everolimus improve pulse wave velocity in stable de-novo renal allograft recipients?
Absolute Event Rate: -0.37% vs 0.89%
Switching from cyclosporine A to everolimus in renal allograft recipients prevents the progression of arterial stiffness observed with continued cyclosporine A therapy.
May support switching cyclosporine A to everolimus to prevent arterial stiffness progression in renal allograft recipients; extends RCT evidence on calcineurin inhibitor alternatives.
BACKGROUND: Cardiovascular mortality is extraordinarily high in renal allograft recipients and accounts for almost half of all allograft losses. Whereas the immunosuppression with calcineurin inhibitors is associated with an increased cardiovascular risk, beneficial effects of mammalian target of rapamycin inhibitors on the vascular system are suspected. METHODS: In a randomized clinical trial, we evaluated the impact on pulse wave velocity (PWV) of a switch from cyclosporine A (CsA) to everolimus (EVR), 6 months after transplantation, in 27 stable de-novo renal allograft recipients. PWV was assessed before and after randomization to the different immunosuppressive protocols at 6 and 15 months post-transplantation, respectively. Seventeen out of 27 patients included in the analysis were switched to EVR; 10 out of 27 were kept on CsA. RESULTS: The switch of immunosuppressive therapy from CsA to EVR resulted in stable PWV (9.50+/-1.92 vs. 9.13+/-1.62 m/s, DeltaPWV= -0.37+/-1.14 m/s, P=0.16), whereas a significant increase of PWV (9.93+/-1.94 vs. 10.8+/-2.24 m/s, DeltaPWV=0.89+/-1.47 m/s, P=0.03) was observed in patients on continued CsA therapy. CONCLUSION: In renal allograft recipients, the prolonged treatment with CsA was associated with a significant increase of PWV whereas no further deterioration of large vessel compliance was observed in patients that were switched to EVR 6 months post transplantation. The cardiovascular risk profile in stable de-novo renal allograft recipients might therefore be positively impacted by an early switch of the primary immunosuppressive therapy from CsA to EVR.
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Seckinger et al. (2008) conducted an RCT in stable de-novo renal allograft recipients (n=27). Everolimus vs. Cyclosporine A was evaluated on Pulse wave velocity (PWV). Switching from cyclosporine A to everolimus stabilized pulse wave velocity (change -0.37 m/s, P=0.16), whereas continued cyclosporine A led to a significant increase (change 0.89 m/s, P=0.03).
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