Paclitaxel-eluting devices in peripheral vascular interventions

Background: Paclitaxel is a cytostatic agent that is widely used in oncologic treatment. It has also showed promising results in combating vascular restenosis. It is delivered via drug-coated balloons (DCB) or drug-eluting stents (DES). Peripheral artery occlusive disease (PAD) affects approximately 200.000.000 people worldwide. Therapeutic options for occluded or stenosed arteries include open surgical bypass and endovascular percutaneous treatment and balloon dilatation. Both induce intimal hyperplasia as a biological response: as part of the arterialization and surgical trauma of the graft in the first, and as an intimal injury response in the latter. Hyperplasia can lead to restenosis. Dialysis through an arteriovenous fistula (AVF) is the standard of care in patients with chronic kidney disease (CKD). The fistula is created by anastomosing a vein to an artery, thus exposing the vein to arterial pressure and flow. The biological response in the venous wall is complex, and is further aggravated by the often numerous comorbidities of dialysis patients. Intimal hyperplasia in the venous segment of the fistula is a frequent cause for stenosis and AVF failure. The aim of this thesis was to investigate the potential benefit of paclitaxel for prevention of restenosis and maintaining conduit patency in bypass vein grafts and arteriovenous fistulae, and furthermore to compare patency of leg revascularization with paclitaxel eluting stents and open bypass surgery. Materials: The thesis consists of four parts. First, 93 consecutive cases of DCB treated restenoses in native arteries, vein grafts, and AVFs were retrospectively analyzed for potential improvement in the target lesion revascularization (TLR) free survival after DCB. Second, the effect of DCB for vein graft restenosis was analyzed in a prospective single-center randomized controlled trial (RCT). Primary endpoint was freedom from TLR Third, the effect of DCB on AVF stenosis was investigated in a RCT. Primary endpoint was freedom from TLR. Fourth, DES and open prosthetic femoropopliteal above-knee bypass surgery were compared in a prospective, multi-center RCT. Primary endpoint was stent/conduit patency. Results: Study I: The overall time from DCB to endpoint was 572 days, compared to 240 days from previous BA to DCB (P