Drug-eluting balloons: where are we and what are the problems?

Abstract

The starting point of percutaneous transluminal coronary angioplasty was defined by Andreas Gruntzig in 1977 [1]. He developed the novel technique of revascularization and established a new speciality – interventional cardiology. Since that time, interventionalists have been confronted with the problems of vessel recoil during the procedure and restenosis within the first 6 months of balloon angioplasty. In spite of progress in some indications, in others these challenges have lost nothing of their significance, motivating investigators to pursue their research efforts with a view to finding new strategies for overcoming these difficulties. Stents proved to be a significant advance in reducing the frequency of restenosis by eliminating elastic recoil and negative remodeling at the treatment site [2]. However, neointimal proliferation is not prevented by stenting, and thus in-stent restenosis became a ‘new’ disease, especially in some patient populations such as diabetics or in certain lesions such as bifurcation, long lesions, lesions in small vessels, total occlusions and diffuse disease [3]. The systemic administration of anti-inflammatory, antiproliferative, anticlotting or other agents before or after balloon dilatation was shown to effectively reduce neointimal hyperplasia in animal models. Clinical use in humans, however, failed to result in adequate restenosis prevention [4]. The advent of drug-eluting stents (DESs) marked a decisive advance, enabling direct transfer of drugs to the target site and prolonged exposure of the vessel wall. Sirolimus and paclitaxel were shown to be effective pharmacological inhibitors of neointimal hyperplasia in vitro and in vivo [5,6]. Stents coated with these agents were successfully used in both the coronary arteries [7] and below the knee [8]. By contrast, use of these stents were not found to be superior to bare-metal stents in femoral and popliteal arteries or in patients with severe diffuse disease and long, complicated lesions [9]. The occurrence of late stent thrombosis, caused by incomplete endothelization of the stent struts and an inflammatory response to the polymer matrix, considerably limited the use of DES [10,11]. Coating paclitaxel onto the surface of conventional percutaneous transluminal coronary angioplasty balloon catheters with a new coating technique that provides immediate drug release upon inflation was a new approach to preventing restenosis without having to implant a stent. The drug is transferred to the dilated segment when the balloon is inflated. An effective local drug concentration is achieved with very low systemic exposure. Paclitaxel admixed to a small amount of the hydrophilic x-ray contrast medium iopromide (Ultravist) emerged as a very effective coating matrix from numerous in vitro and in vivo experiments investigating different coating techniques, the adhesion of paclitaxel to the balloon surface while the catheter is advanced to the lesion, and the release of the active agent into the vessel wall during balloon expansion [12,13]. Balloon catheters coated in this way have a paclitaxel dose of 3 μg/mm of balloon surface and are marketed as Paccocath (Bayer Schering Pharma AG, Germany). 1Department of Radiology, Charite – Universitatsmedizin Berlin, Chariteplatz 1, 10117 Berlin, Germany 2Clinic for Internal Medicine III, Cardiology, Angiology and Intensive Care, University Hospital of Saarland, Homburg/Saar, Germany †Author for correspondence: Tel.: +49 304 5053 9076 Fax: +49 304 5052 7993 E-mail: beatrix.schnorr@charite.de