Introduction
Hemodialysis is the most common treatment of patients with end-stage renal disease. In most of them the circulation is accessed through an arteriovenous fistula (AVF) or a graft (AVG) created on the upper limb (1,2). Although there is no better entry point for dialysis than a functional dialysis access (DA) on upper limb, its performance is far from perfect with nearly all patients requiring at least one percutaneous intervention with a subsequent primary patency rate of 23% at 12 months (3–5).
Despite great effort that had been devoted to improving the durability of DA, for long percutaneous transluminal angioplasty (PTA) had been the mainstay of DA stenosis treatment. The proposed deployment of a stent in the stenosis was initially met with little success. Further studies showed that only nitinol stents might deliver improved patency rates (6,7). Further development based on the promising bare nitinol stent was crowned by the design of a covered stent graft. Initial promising results were confirmed in a randomized multicenter trial that showed significant improvement of overall patency rates and freedom from subsequent interventions in short-term (8). The benefit of a stent graft deployment in a stenosed DA had been replicated in further studies and scenarios (9). However, the efficacy of the use of stents or stent grafts in the treatment of DA had been questioned due to the high cost of the devices and a limited number of randomized studies with long-term endpoints (10).
The objectives of this independent study were to compare three options for the treatment of failing AVG due to restenosis in the venous anastomosis or the adjacent segment of the outflow vein by PTA, deployment of a stent, or a stent graft with regard to primary and secondary patency rates, the number of therapeutic interventions (either PTA ± thrombolysis) required to maintain vascular access patency, and the cost of maintaining the vascular access.
Results
The patients were 64±12 years old and 41 (71%) were women. There was no significant difference between the groups in the baseline data (Table I). In all patients, the primary intervention was technically successful (Table II). During a median follow-up of 22.4 [interquartile range (IQR)=5.7] months patients with PTA, stent, or stent graft required 3.1±1.7, 2.5±1.7, or 1.7±2.1 (P=0.031) secondary PTA interventions, respectively. The primary patency rates were 0, 18, and 65% at 12 months and 0, 18, and 37% at 24 months in the PTA, stent, and stent graft group respectively (P<0.0001; Fig. 3). The secondary patency rates were 94, 84, and 89% at 12 months and 94, 84, and 79% at 24 months (P=0.58; Fig. 4). The cost of the procedures in the first two years was €7,900±€3,300 in PTA group, €8,500±€4,500 in stent group, and €7,500±€6,200 in stent graft group (P=0.45).
Survival analysis showed that patients with stent graft had better primary patency rates (P<0.0001; Fig. 3), but there was no difference in the secondary patency rates among the groups (P=0.58; Fig. 4). Multivariable Cox regression analysis identified the following predictors of primary patency: residual stenosis after initial PTA [hazard ratio (HR)=1.048; 95% CI 1.013 to 1.084; P=0.007], diameter of the reference segment adjacent to the stenosis (HR=0.498; 95% CI 0.306 to 0.813; P=0.005), and outflow to the superficial venous system vs. deep venous system (HR=0.457; 95% CI 0.233 to 0.894; P=0.022) with model significance of P=0.005 (Table III).
Discussion
In this study, we compared the mid-term performance of PTA, bare stent, and stent graft in the treatment of restenosis in the venous anastomosis or the adjacent segment of the outflow vein of upper limb AVGs. We showed that patients with stent graft required less subsequent PTA interventions but the reduction in cost was not statistically significant. We further identified predictors of primary patency rate.
Hemodialysis is the most common treatment of patients with end-stage renal disease. Maintaining dialysis access is necessary for all patients undergoing ambulatory hemodialysis on a regular basis. In most cases, a DA is the preferred long-term or permanent solution (1,2). The majority of DA failures occur due to stenosis or occlusion and can be repaired by percutaneous intervention including PTA and local thrombolysis with initial success rates above 90% and primary patency rates of 23% at 12 months (4,5,12,13). The culprit stenosis that leads to malfunction of AVG can be identified in the anastomosis in half of the patients with prosthetic AVGs. In patients with autogenous AVFs it is more common in the outflow vein. Stenosis in failing AVGs is attributed to intimal hyperplasia due to increased wall shear stress and other mechanisms with secondary thrombosis caused by decreased flow velocity and stasis (3).
Maintaining failing DA is a matter of finding a line between the requirement of repeated percutaneous interventions and surgical correction or a redo procedure (14). Nearly all patients with DA require at least one percutaneous intervention (14). Early resolution of DA stenosis improves the functioning of the circuit, but randomized trials were unable to demonstrate its positive effect on DA survival (15,16). Lessons have been drawn from other vascular interventions, and stents and stent grafts have been tested in DAs in the treatment of stenosis, aneurysms and ruptures initially in off-label settings (17).
A percutaneous approach to DA stenosis by PTA has been long established as the best treatment in most cases and used as the gold standard (14,18,19). The primary patency rates after PTA of DA regardless of location (arm, forearm) vary widely in the literature and are about 25–30% for AVG and 67% for AVF at 1 year (3). Up to 70% of patients require a second intervention within one year (5,20). Secondary patency rates usually with multiple interventions are about 82% at one year and 70% at two years (3,8).
Initial attempts to improve patency rates of AVF by placement of bare stents have been disappointing and their hypothesized advantage over PTA alone did not materialize (21,22). Only nitinol stents showed improved flow in the AVF with and better patency rates with a pooled relative risk of 0.79 (2,6,7). Compared to stainless steel, nitinol (nickel-titanium alloy) stents do not shorten during deployment (23).
Further development based on the promising bare nitinol stent resulted in the design of a covered stent graft that was used in a randomized multicenter trial by Haskal et al who compared short-term patency rates in 190 patients with venous anastomotic stenosis in a prosthetic AVG (8). In their study, PTA with the placement of a stent graft showed significant improvement in overall primary patency rates of the AVG and freedom from subsequent interventions at six months compared to PTA alone (32% vs. 16%) (8). The advantage of a stent graft over PTA was later confirmed in other studies as well (9). Carmona et al compared primary patency rates in patients with failing grafts due to stenosis at the graft to vein anastomosis between PTA and heparin bonded stent graft and reported improved primary patency rates from 9 to 42% and an increased proportion of functional grafts from 36 and 88% at 12 months (24). Both rival stent grafts (nitinol stents covered with ePTFE), the Viabahn® and Fluency® were compared in a study by Schmelter et al (25), who did not prove any difference in primary and secondary patency rates in the treatment of stenosed AVGs and AVFs. In their study, the primary patency rates were 31% at 12 months and 19% at 24 months. Our results with 65 and 37% primary patency rates at 12 and 24 months in the stent graft group and only prosthetic AVGs compare favorably with the results from Schmelter et al (25). The success rate of the deployment of stents and stent grafts in our study is comparable to other studies that consistently report high rates near 99% confirming the safety of both approaches (8,25).
The effect of antiplatelet agents and their risk to benefit ratio in dialysis patients is poorly understood especially in AVGs and their general use for preventing AVG thrombosis is therefore not recommended due to lack of supporting data (3,26,27). Their use after placement of stent graft in stenosed dialysis access has not been included in the protocol of previous studies and left on the discretion of the referring physician (8,25). In our study, the protocol required dual antiplatelet therapy after deployment of stent or stent graft. We believe that this might have improved their performance compared to the PTA group.
The comparison of primary and secondary patency rates after intervention should be viewed in the perspective of study design. Intensive follow-up programs with tight monitoring of the vascular access and early intervention artificially decrease the primary patency rates (10). Moreover, lower patency rates can be expected in AVGs, younger DA, in the presence of longer lesions, and residual stenosis after PTA (25,28). The present study confirmed that greater residual stenosis after initial PTA is a risk factor and identified further two factors: Smaller diameter of the reference segment adjacent to the stenosis and the use of a deep vein as the outflow.
Numerous approaches to the management of stenosed or malfunctioning DA have also been compared on the cost-effectiveness basis. The debated intensive surveillance program has an incremental net cost for a modest decline in DA thrombosis and is less efficient than increasing the proportion of autogenous fistulas (13,29). The cost-effectiveness of stents and stent grafts in the treatment of DA stenosis has been questioned due to the high cost of the devices and a limited number of randomized studies with long-term endpoints (10). Our study showed that deployment of a stent graft results in decreased number of subsequent PTAs, but the reduction in cost for maintaining AVG patency in our country was not significant. We estimate that in countries such as the USA or India the deployment of a stent graft in this scenario would reduce the cost of maintaining the access from the payer's perspective by a greater margin due to higher ratio between the procedure reimbursement rates and the price of the stent graft, even more than predicted by Dolmatch et al (30). Nevertheless, the sole reduction of the number of PTAs can be regarded as a clear benefit to the comfort of the patient.
In conclusion, this study confirms that treatment of failing dialysis vascular access due to restenosis in the anastomosis or the outflow vein by the deployment of a stent graft significantly improves its primary patency rate and decreases the number of secondary PTA interventions in comparison with PTA and deployment of a stent. The cost analysis showed that the reduction in cost for maintaining AVG patency is not statistically significant. The present study confirmed that greater residual stenosis after initial PTA is a risk factor and identified further two: Smaller diameter of the reference segment adjacent to the stenosis and the use of a deep vein as the outflow. Finally, the safety of all three compared approaches was confirmed.
The present study has several limitations. Firstly, the sample size is relatively small. Secondly, the study groups are heterogeneous in term of the location of the restenosis. Thirdly, only one type of stent graft was used. Fourthly, dual antiplatelet therapy was required in the stent and stent graft groups only, but patients from the PTA group received or continued at least one antiplatelet agent or continued their anticoagulation therapy. Lastly, the cost analysis pertains to the author's country.