New Drug-Coated ePTFE Artificial Vessel for Dialysis

In recent years, advances in dialysis therapy have significantly extended the lifespan of patients with end-stage renal disease, from more than a decade to several decades. Hemodialysis patients are required to undergo treatment three times per week. To achieve efficient blood purification within a limited period, it is essential to secure vascular access that is both easy to cannulate and capable of maintaining sufficient blood flow.
Therefore, patients typically undergo arteriovenous fistula (AVF) creation or implantation of a polytetrafluoroethylene (PTFE) vascular graft (Fig. 1). However, regardless of the type of vascular access, neointimal hyperplasia often develops over time, leading to luminal stenosis and insufficient blood flow. As a result, repeated reconstruction of new vascular access routes becomes necessary.
In Japan, the medical costs associated with such repeated interventions have been increasing year by year, placing a significant burden on the healthcare insurance system. Furthermore, these procedures impose substantial physical and financial burdens on patients. Despite these challenges, effective therapeutic strategies for vascular access failure have not yet been established.

According to a facility survey conducted at the end of 2022, the number of dialysis patients in Japan was 347,474, corresponding to 2,781 patients per million population. Among these, 89.7% are managed using arteriovenous fistulas (AVFs) as vascular access. In contrast, patients with poor superficial vessels or conditions such as arterial occlusive disease require PTFE vascular graft implantation, which accounts for approximately 7.1% of cases. This proportion is considered lower than that reported internationally.
In general, AVFs provide longer patency and are therefore the preferred option for dialysis patients. However, when PTFE vascular grafts are used, their patency duration is typically much shorter. Approximately 50% of vascular access routes using artificial grafts develop luminal stenosis within one year due to neointimal hyperplasia, resulting in decreased blood flow and eventual vascular access failure. The patency rate at two years falls to less than 10%, necessitating the creation of new vascular access routes.
The total cost required to establish a new vascular access route is approximately 300,000 yen, with an out-of-pocket expense of around 90,000 yen under a 30% copayment.

The use of PTFE vascular grafts as vascular access routes for dialysis patients has been increasing year by year, accompanied by a rise in the number of reinterventions required due to vascular access failure. This trend imposes a significant burden on both patients and the healthcare insurance system.
As demonstrated in our research, chymase inhibitor-coated PTFE vascular grafts markedly suppress neointimal hyperplasia compared with non-coated grafts, as observed six months after carotid arteriovenous implantation in canine models. These findings suggest that clinical application of chymase inhibitor coating technology has the potential to substantially prolong the patency of PTFE vascular access grafts in dialysis patients.
Furthermore, in our previous studies evaluating the effects of oral administration of chymase inhibitors, the treatment significantly reduced not only neointimal hyperplasia within the graft lumen but also thrombus formation at the sites of intimal thickening compared with untreated groups. These results indicate that this approach may also overcome one of the major drawbacks of PTFE grafts—their high thrombogenicity.
Taken together, coating PTFE vascular grafts with chymase inhibitors is expected to significantly extend their usable lifespan in clinical practice. This advancement may not only reduce the economic burden on patients but also contribute to alleviating the growing financial strain on healthcare systems.