Paclitaxel – A Tool to Prevent Stenosis in Vascular Access for Haemodialysis?

Paclitaxel has an antiproliferative effi cacy against a variety of malignant cell lines and against smooth muscle cells [1, 2] . Hong et al. [3] reported on the placement of paclitaxel-eluting stents to reduce coronary in-stent restenosis in pigs. As an alternative to this ‘inside-out’ drugeluting stent approach, Melhem et al. present an ‘outsidein’ perivascular approach. They could demonstrate ‘that the paclitaxel polymer wraps were mechanically stable with a burst release phase followed by a slower continuous release phase’. In addition, they showed that the ‘released paclitaxel retains its physicochemical and biological properties and is able to inhibit the proliferation of smooth muscle cells, endothelial cells and fi broblasts in vitro’. It seems extremely unlikely that the local delivery of paclitaxel would result in any systemic toxicity. A still critical issue in any delivery system, although a fascinating aspect, is the ‘need to match the temporal profi le of drug release to the biologic sequence of events that characterize the disease process’. Finally, the authors speculate that ‘a potent antiproliferative drug milieu at the site of vascular injury for this prolonged period of time could result in a permanent alteration of cell types at the graft-vein or the artery-vein anastomosis, such that neointimal hyperplasia may not occur even in the absence of paclitaxel release after the complete release of paclitaxel from the EVA polymer wrap’. A well-functioning vascular access – an arteriovenous fi stula (AVF) or an arteriovenous graft (AVG) – is the lifeline for the hemodialysis patient. Access dysfunction is mainly caused by venous stenosis which fi nally results in access thrombosis. In forearm AVF, postanastomotic stenoses are observed in about 50% of patients; the underlying mechanism still remains speculative. In addition, AVF stenoses occur in scarred and narrowed venous segments due to cannulations during the predialysis period. Repeated cannulation of the identical area for dialysis access can lead to stenoses and aneurysms. In AVG, stenoses are predominantly observed at the graft-vein anastomosis caused by venous neointimal hyperplasia (VNH) which consists of smooth muscle cells, fi broblasts and myofi broblasts and a microvessel formation within the neointima causing a substantial economic burden and clinical morbidity. Numerous surgical and interventional therapeutical techniques were introduced. It therefore makes sense to look for an effective prevention of VNH. Dr. Melhem and co-workers from Cincinnati, USA, report on ‘Development of a local perivascular paclitaxel delivery system for hemodialysis vascular access dysfunction: Polymer preparation and in vitro activity’. They succeeded in developing a paclitaxel-loaded ethylene vinyl acetate (EVA) polymer wrap for local drug delivery in a perivascular confi guration in a pig AVG model. Published online: February 7, 2006