Key result
Everolimus with reduced CNI shows no benefit over standard therapy for CAV progression but increases calcification.
Why the study?
Does everolimus with reduced CNI exposure reduce morphological progression of cardiac allograft vasculopathy in maintenance heart transplant recipients compared to standard CNI therapy?
RCT (n=78)
Yes
Does everolimus with reduced CNI exposure reduce morphological progression of cardiac allograft vasculopathy in maintenance heart transplant recipients compared to standard CNI therapy?
Absolute Event Rate: 1.9% vs 1.6%
p-value: p=0.65
Conversion to everolimus with reduced CNI in heart transplant recipients is associated with increased calcified and necrotic intimal components in cardiac allograft vasculopathy, particularly in patients with longer time since transplant.
Should not yet alter CNI minimization in heart transplant recipients; leaves open whether increased necrotic and calcified plaque affects outcomes.
In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 ± 4.0 vs. 0.3 ± 3.1%; p = 0.02) and necrotic component (6.5 ± 8.5 vs. 1.1 ± 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.
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Arora et al. (2012) conducted an RCT in Maintenance heart transplant (HTx) (n=78). Everolimus with reduced calcineurin inhibitor (CNI) exposure vs. Continued standard CNI-therapy was evaluated on Quantitative CAV progression (plaque index) (p=0.65). Everolimus with reduced CNI exposure resulted in similar quantitative CAV progression compared to standard CNI therapy (plaque index 1.9% vs 1.6%; p=0.65), but increased calcified and necrotic components.
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