Current status on drug-eluting devices in dialysis access

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Dialysis access fistulae and grafts are life-saving in patients with renal insufficiency and failure. Numbers of patients requiring haemodialysis have continued to rise over recent decades and are expected to rise further in the future, making interventional radiology an integral part of this life-saving procedure, writes Marcio Das, Maastricht, The Netherlands.

Arteriovenous fistulae (AVF) or arteriovenous grafts (AVG—usually made of polytetrafluoroethylene [PTFE])—are surgically placed and need to maintain a blood flow of at least 400–500mL/min in order to allow proper haemodialysis function. Problems occur due to the unphysiological blood pressure which induces wall stress on the venous vessel wall, inducing tangential and shear wall stress, which may consecutively lead to the development neointimal hyperplasia with consecutive stenosis resulting in reduced blood flow. Occurrence of stenosis frequently requires treatment—usually making use of balloon angioplasty and, in the central venous system, also resulting in stent placement as ultima ratio.

In patients with suspected stenosis, percutaneous balloon angioplasty usually is the first method of choice, although primary patency rate after six months can be lower than <50%. Standard pressure balloons are primarily used. In recurrent stenosis, high pressure balloons or cutting balloons are often used, while stenting (including stent grafts) should be initially avoided for as long as possible, although some authors have also documented good results using stent grafts and higher patency rates using cutting balloons. These techniques are usually more aggressive and therefore represent mostly treatment options in patients with restenosis.

Drug-eluting balloons and drug-eluting stents have been successfully implemented in the treatment of coronary artery disease. Using drugs like paclitaxel or everolimus, which are coated to the balloon, reactions induced in the vessel wall can be reduced—especially suppression of proliferation of smooth muscle cells. These drugs belong to the group of cytotoxic agents (paclitaxel) or immunosuppressant (sirolimus) and therefore aim to reduce building of neo-intima, which consecutively causes stenosis. The challenge is to bring enough of the agent to the vessel wall at the location of the stenosis and to have enough bioactive drugs at the place over a period of time. In drug-eluting balloons, the drug is usually put into a polymer matrix which degrades when the material comes into contact with the vessel wall. Usually 2.5–3.5μg of the therapeutic agent is placed on the balloon per mm2. Appropriate sizing is therefore necessary for sufficient contact of the agent with the treatment area. As dialysis fistulae often show great variability in vascular configuration, the choice of the optimal material can be challenging, especially as larger DEB (>7mm) are still missing or need to be custom made.

Initial studies using drug-eluting balloons in comparison to treatment with standard balloon angioplasty did show reduced restenosis rates of 12% compared to 28% in peripheral artery disease. In dialysis fistulae evidence is less available, but current results in small patient cohorts are encouraging. Katsanos/Kitrou et al performed a prospective randomised trial comparing drug-eluting balloons and standard balloon angioplasty in arteriovenous fistulae and arteriovenous grafts using paclitaxel-coated balloons, which showed a primary patency rate of 70% versus 25%. A recent large retrospective study by Swinnen et al showed a reintervention-free percentage at 12 months of 69% for the use of drug-eluting balloons, while in patients without use of drug-eluting balloons only 12% did not need intervention during one-year of follow-up. In a study of 26 patients by Patane, very high primary patency rates of up to 96% after six months were shown as well as 58% after 24 months, which is very high compared to standard balloon angioplasty. Massmann et al could show a significantly better “freedom from target lesion revascularisation by the use of drug-eluting balloons in central vein stenosis. Interval to restenosis was nine months with the use of drug-eluting balloons and four months with use of a standard balloon. Recently, the results of a prospective randomised trial were published by Kitrou et al. Forty patients were randomised to either treatment with a standard balloon angioplasty or treatment using a drug-eluting balloon. Patients treated with drug-elution had a significantly longer target lesion revascularisation-free survival. A prospective randomised multicentre trial is currently under way (Karunanithy et al) aiming to include 211 patients, randomised to post-plain balloon treatment with or without drug-eluting balloons. Patients will be followed for one year to assess target lesion patency. As costs play an important role, cost-effectiveness is always of great concern. Initial studies have presented results showing a cost benefit of drug-eluting balloons compared to plain balloons alone of approximately €1,000, mainly as a result of longer patency rates and less frequent re-intervention.

Initial results for drug-eluting balloons are very promising. Unfortunately, data is still based on small sample sizes, heterogeneous input values and outcome measures. Yet, large, ideally prospective randomised multicentre trials are lacking, but are under way. Further research is essential in addressing several unanswered issues. Challenges remain such as missing spectrum of different drug-eluting balloons in terms of sizing, questions about optimal treatment of different anatomical locations (eg. venous anastomosis vs. central vein stenosis) and unclear knowledge about primary use or secondary use of drug-eluting balloons after initial percutaneous transluminal angioplasty.

Marco Das is part of the Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands

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