SIroliMus Coated angioPlasty Versus Plain Balloon Angioplasty in the tREatment of dialySis acceSs dysfunctION (IMPRESSION)

Dialysis vascular accesses such as Arteriovenous Fistula (AVF) and Arteriovenous Grafts (AVG) are surgically created vasculatures used for hemodialysis in patients with End-Stage Renal Disease (ESRD). A functioning dialysis vascular access is critical to the delivery of life-saving hemodialysis (HD) treatment to these patients. Unfortunately, neointimal hyperplasia frequently occurs within the dialysis vascular access, resulting in stenosis, poor flow and thrombosis with loss of function. The durability of both AVF and AVG are poor, with an almost 50% failure rate after a median lifetime of 3 to 7 years for AVF and 12 to 18 months for AVG. Vascular access failure is the most common reason for hospitalization among HD patients. The global healthcare costs for treating vascular access-related complications amount to USD 18 billion, and in USD 1 billion in the US alone. These figures are set to increase, due to the increase in the prevalence of access interventions and hemodialysis patients globally. Singapore has one of the highest ESRD rates in the world and the investigators are facing an increasing number of patients with ESRD and the majority of the patients opting for hemodialysis as their treatment modality. As such, vascular access-related complication is set to be a major contribution of healthcare cost in our nation.

The current gold standard therapy for the treatment of stenosis in dialysis access is plain balloon angioplasty (BA). Despite its widespread availability and minimally invasive nature, the mid- and long-term patency with BA in patients with ESRD is poor. The reported average primary patency after BA is around 40-50% at 1 year. Multiple repeated angioplasty is required to maintain the patency of the vascular access. Hence, there is an urgent clinical need to improve the patency of dialysis vascular access.

Recently, the use of stents, in particular stent graft, has been shown to be superior to angioplasty for stenosis occurring at the site of venous anastomoses of an AVG. The incidence of patency of the treatment area was significantly greater in the stent-graft group than in the balloon-angioplasty group (51% vs. 23%, P<0.001), as was the incidence of patency of the access circuit (38% vs. 20%, P=0.008) at 6 months. For cephalic arch stenosis in AVF, the use of stent graft has also been shown to be superior to bare metal stent. The 6 month primary patency for stent graft and bare stent was 81.8 and 39.1%, respectively. One-year primary patency for stent graft and bare stent was 31.8 and 0.00%, respectively (P = 0.002). However, the use of stent graft for the management of dialysis vascular access is not without any concern. In particular, re-stenosis can occur within the stented segment (post stent 12-month primary patency is 46%), resulting in the need for repeat angioplasty. Future stent deployment in the re-stenotic segment may also not be feasible due to the presence of the stent. Moreover, the presence of a stent can impede future surgical revision or new access creation within the same vessel.

Paclitaxel-coated balloon angioplasty (PCBA) has also been shown recently to be superior to plain BA in the treatment of stenosis in dialysis vascular access. This is because the very intervention used to treat the underlying stenosis by plain BA can induce vascular injury and accelerate intimal hyperplasia, resulting in rapid restenosis and the need for repeated procedures to maintain vessel patency. By releasing Paclitaxel, which is an anti-proliferative drug, locally into the vessel wall during balloon contact, it will blunt the acceleration of intimal hyperplasia response, resulting in improved primary patency after angioplasty. Additionally, unlike stents, PCBA does not leave a permanent structure that may impede future surgical revision. In a small 40 patient pilot study, the primary unassisted patency in the PCBA group was significantly better than the plain BA group at 6 (70 % versus 25 %) and 12 months (35 % versus 5 %, p <0.001) respectively. Recent randomized control trials have also shown the superiority of PCBA over plain balloon angioplasty in the treatment of stenosis in dialysis vascular access. However, concerns had also arisen recently in the use of PCBA. In large lower limb studies involving the use of PCBA, meta-analysis had revealed an increased risk of death in patients that are treated with PCBA or paclitaxel-coated stent. This had led to warning from the United States Food and Drug Administration (FDA) and the issue of guidelines from the interventional societies

Sirolimus coated balloon (SCB) is the new generation of drug-eluting balloons available in the market. Compared to Paclitaxel, sirolimus is cytostatic in its mode of action with a high margin of safety. It has a high transfer rate to the vessel wall and effectively inhibits neointimal hyperplasia in the porcine coronary model. In the coronary artery interventions, preliminary clinical studies using SCB have also shown excellent procedural and 6-month patency.