Internal Med Medical News about everolimus and zotarolimus eluting stents

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Rapamycin promotes arterial thrombosis in vivo: implications for everolimus and zotarolimus eluting stents
European Heart Journal, 07/02/09

Camici GG et al. – Rapamycin increases tissue factor (TF) activity and promotes arterial thrombosis in vivo at concentrations relevant in pts undergoing drug-eluting stents (DES) implantation; this effect may increase the thrombogenicity of DES. Since everolimus and zotarolimus augment endothelial TF expression and activity in vitro in a similar manner as rapamycin, these findings may also be relevant for second generation DES.

Methods

Study of effect of mammalian target of rapamycin (mTOR) inhibition on TF activity and thrombus formation in vivo
Investigation of whether second-generation DES substances everolimus and zotarolimus have an effect on endothelial TF expression
Use of a mouse carotid artery photochemical injury model

Results

In mouse model, rapamycin (182 ± 27.5 µg/L) decreased time to thrombotic occlusion by 40%, increased TF activity, and abrogated p70S6K phosphorylation vs controls
In vitro, rapamycin, everolimus, and zotarolimus (each 10–7 mol/L) enhanced TNF-{alpha}-induced TF expression by 2.2-, 1.7-, and 2.4-fold, respectively, which was paralleled by an increase in TF surface activity
Similar to rapamycin, everolimus and zotarolimus abrogated TNF-{alpha}-induced p70S6K phosphorylation under these conditions

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