Potential solutions to the current problem: coated balloon.

Restenosis prevention continues to be a challenge in interventional cardiology. Clinical trials on drug eluting stents (DES) suppressing neointimal proliferation by sustained release of antiproliferative drugs have shown excellent results in reducing restenosis. DES are well accepted in the prevention and therapy of coronary restenosis. Meanwhile, concerns have been raised that DES while being effective in reducing restenosis may be associated with an increased incidence of late thrombotic complications or death. Restenosis caused by neointimal proliferation is a slow process, suggesting that prolonged local drug administration is necessary for effective inhibition. DES are characterised by a sustained drug delivery due to special features for slow release, mostly polymer matrixes. In this case, sustained drug release is essential because drug distribution from a DES to the arterial wall is inhomogeneous1. About 85% of the stented vessel wall area is not covered by the stent struts resulting in low tissue concentrations of the antiproliferative agent in these areas. Cell culture experiments indicate that low drug concentrations require much longer exposition times to achieve sufficient inhibition of cell proliferation than higher concentrations2-5. Therefore, high drug concentrations on the stent struts including controlled and sustained release are mandatory for stent-based local drug delivery6 with the consequence of delayed and incomplete endothelialisation of the stent struts7. Furthermore, the polymeric matrixes on the stent embedding the antiproliferative drug could induce inflammation and thrombosis8,9. On the other hand, incomplete suppression of neointimal hyperplasia at the stent margins or between the struts may limit the efficacy of DES1,10. Novel concepts to overcome the limitations of DES should avoid sustained drug release from stent struts including polymers or other sustained release technology. The drug-eluting PACCOCATH balloon (DEB) represents a novel option for the treatment of coronary and peripheral arteries. The DEB is a regular angioplasty balloon coated with paclitaxel at a dose of 3 μg/mm2 balloon surface. It requires no special handling. A key feature of the PACCOCATH is to facilitate the transfer of the antiproliferative agent from the balloon surface to the vessel wall during a short inflation time. The coating includes an X-ray contrast medium (iopromide) which improves the solubility of the drug and its transfer to the vessel wall. The basic experiments leading to this device were performed by us based on the surprising discovery that sustained drug release as provided by DES is not a precondition for long lasting restenosis inhibition. The innovative coating technique enables for a controlled dose of paclitaxel to be released during dilatation as soon as the balloon is inflated inside the stenotic artery11. It allows for a homogeneous drug distribution to the arterial wall12. Once exposed cells retain paclitaxel in vivo for six days even if plasma levels were far below the detection limit13. Preclinical studies have shown that brief contact between vascular smooth muscle cells and antiproliferative drugs can result in prolonged inhibition of neointimal proliferation4,5,11,14. It has been shown, that even after a short single dose application on human smooth muscle cell cultures, paclitaxel had a sustained anti-proliferative effect over 14 days without showing cytotoxic effects15. Initial drug concentration as achieved by the DEB is a substitute for sustained release. The drug administered only during the short