IN.PACT AV Access Randomized Trial of Drug-Coated Balloons for Dysfunctional Arteriovenous Fistulae: Clinical Outcomes through 36 Months.

PURPOSE: To present the 36-month outcomes of the prospective randomized IN.PACT AV Access study of participants with obstructive de novo or restenotic native upper extremity arteriovenous dialysis fistula lesions treated with drug-coated balloon (DCBs) or standard percutaneous transluminal angioplasty (PTA) following successful high-pressure PTA. MATERIALS AND METHODS: Participants at 29 international sites were randomized 1:1 to receive an IN.PACT AV DCB (n = 170) or undergo PTA (n = 160). The outcomes through 36 months included target lesion primary patency (TLPP) and access circuit primary patency (ACPP) (composites of clinically driven target lesion or access circuit revascularization and/or access circuit thrombosis), number of reinterventions, and serious adverse events involving the access circuit. RESULTS: TLPP was 52.1% in the DCB group compared with 36.7% in the PTA group through 24 months and 43.1% in the DCB group compared with 28.6% in the PTA group through 36 months (both log-rank P < .001). ACPP was 39.4% in the DCB group compared with 25.3% in the PTA group through 24 months and 26.4% in the DCB group compared with 16.6% in the PTA group through 36 months (both log-rank P < .001). Cumulative incidence of access circuit thrombosis through 36 months was 8.2% in the DCB group compared with 18.3% in the PTA group (log-rank P = .040). Cumulative incidence of mortality through 36 months was 26.6% in the DCB group compared with 30.8% in the PTA group (log-rank P = .71). CONCLUSIONS: This study demonstrated superior TLPP and ACPP with DCBs compared with PTA, with no difference in mortality through 3 years. Access circuit thrombosis was statistically significantly higher in the PTA group at 3 years.

IN.PACT AV access randomized trial: Japan cohort outcomes through 12 months.

PURPOSE: There is a lack of adjudicated and prospectively randomized published outcomes on the use of drug-coated balloons (DCB) to treat dysfunctional arteriovenous fistula in Asian patients. This post hoc subgroup analysis of 112 Japanese participants from the global IN.PACT AV Access trial reports outcomes through 12 months. MATERIALS AND METHODS: Participants were treated with DCB (n = 58) or standard non-coated percutaneous transluminal angioplasty (PTA) balloons (n = 54). Outcomes included target lesion primary patency (TLPP), access circuit primary patency, and safety. RESULTS: Through 6 months, TLPP was 86.0% (49/57) in the DCB group and 49.1% (26/53) in the PTA group (p < 0.001). Through 12 months, TLPP was 67.3% (37/55) in the DCB group and 43.4% (23/53) in the PTA group (p = 0.013). CONCLUSION: In this post hoc analysis of Japanese participants from the IN.PACT AV Access trial, participants treated with DCB had higher TLPP through 6 and 12 months compared with PTA.

Economics of drug-coated balloons for arteriovenous fistula stenosis in Japan and Korea based on the IN.PACT AV access trial.

AIM: The recent IN.PACT AV Access study found drug-coated balloon therapy to be associated with reduced reinterventions compared to percutaneous transluminal angioplasty using standard balloons in the management of arteriovenous fistula stenosis. The economic implications of drug-coated balloon use in Asia, including Japan and Korea, remain unknown. METHODS: A decision-analytic model was developed to calculate strategy-specific costs for Korea and Japan through 5-year follow-up. The analysis assumed maintained therapy benefit beyond current trial follow-up of 1 year in the base case, with several alternative scenarios explored in sensitivity analysis. Costs were derived from claims and reimbursement data, and projections were evaluated at 3 and 5 years post-index procedure. RESULTS: Model-projected access circuit reintervention events for drug-coated versus standard balloons were 1.70 versus 2.76 (-1.06) and 2.53 versus 4.10 (-1.57) at 3 and 5 years in the base case. Corresponding 3- and 5-year costs were ₩6 211 103 versus ₩7 605 553 (-₩1 394 451) and ₩7 766 051 versus ₩10 124 954 (-₩2 358 904) in Korea, and ¥1 469 824 versus ¥1 504 161 (-¥34 337) and ¥1 956 931 versus ¥2 106 632 (-¥149 701) in Japan. In scenario analyses, drug-coated balloons remained cost saving at 3- and 5-year follow-up in Korea, but required up to 5 years to reach cost-savings in Japan. Drug-coated balloon use in reinterventions increased projected savings, as did younger treatment age. CONCLUSION: Treatment of arteriovenous fistulas with the IN.PACT AV drug-coated balloon, based on preliminary data, may lead to meaningful reductions in reintervention costs that would render it cost-saving at timeframes of around 1 year in Korea and between 3 and 5 years in Japan.

IN.PACT AV Access Randomized Trial: 12-Month Clinical Results Demonstrating the Sustained Treatment Effect of Drug-Coated Balloons.

PURPOSE: To present the 12-month outcomes of the IN.PACT AV Access Study, a prospective, single-blind trial enrolling participants with obstructive de novo or restenotic native upper extremity arteriovenous dialysis fistula lesions treated with a drug-coated balloon (DCB) or percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: After successful high-pressure PTA, participants at 29 international sites were randomized 1:1 to treatment with an IN.PACT AV DCB (n = 170) or standard uncoated PTA (n = 160). Outcomes at 12 months include target lesion primary patency (TLPP), defined as freedom from clinically driven target lesion revascularization or access circuit thrombosis; access circuit primary patency; number of reinterventions; and adverse events involving the access circuit. RESULTS: At 12 months, TLPP was 63.8% (90/141) in the DCB group compared with 43.6% (61/140) in the PTA group (P < .001). The total number of reinterventions required to maintain TLPP through 360 days was 93 in the DCB group and 144 in the PTA group, with a 35.4% reduction in reinterventions when DCB was used. Access circuit thrombosis occurred in 2.9% (4/138) of the participants in the DCB group and in 6.2% (8/129) of those in the PTA group (P = .19). Time to TLPP was assessed using a multivariable analysis to identify the factors associated with loss of patency. The treatment device was the independent predictor with the largest effect, with a hazard ratio of 0.42 (95% confidence interval, 0.29-0.60; P < .001). CONCLUSIONS: TLPP was statistically significantly higher with DCBs than with standard PTA at 12 months, demonstrating the sustained and superior effectiveness of this device for the treatment of dysfunctional arteriovenous dialysis fistulae.

Drug-Coated Balloons for Dysfunctional Dialysis Arteriovenous Fistulas.

BACKGROUND: Standard percutaneous transluminal angioplasty is the current recommended treatment for dysfunctional hemodialysis fistulas, yet long-term outcomes of this treatment are poor. Drug-coated balloons delivering the antirestenotic agent paclitaxel may improve outcomes. METHODS: In this prospective, single-blinded, 1:1 randomized trial, we enrolled 330 participants at 29 international sites. Patients with new or restenotic lesions in native upper-extremity arteriovenous fistulas were eligible for participation. After successful high-pressure percutaneous transluminal angioplasty, participants were randomly assigned to receive treatment with a drug-coated balloon or a standard balloon. The primary effectiveness end point was target-lesion primary patency, defined as freedom from clinically driven target-lesion revascularization or access-circuit thrombosis during the 6 months after the index procedure. The primary safety end point, serious adverse events involving the arteriovenous access circuit within 30 days, was assessed in a noninferiority analysis (margin of noninferiority, 7.5 percentage points). The primary analyses included all participants with available end-point data. Additional sensitivity analyses were performed to assess the effect of missing data. RESULTS: A total of 330 participants underwent randomization; 170 were assigned to receive treatment with a drug-coated balloon, and 160 were assigned to receive treatment with a standard balloon. During the 6 months after the index procedure, target-lesion primary patency was maintained more often in participants who had been treated with a drug-coated balloon than in those who had been treated with a standard balloon (82.2% [125 of 152] vs. 59.5% [88 of 148]; difference in risk, 22.8 percentage points; 95% confidence interval [CI], 12.8 to 32.8; P<0.001). Drug-coated balloons were noninferior to standard balloons with respect to the primary safety end point (4.2% [7 of 166] and 4.4% [7 of 158], respectively; difference in risk, -0.2 percentage points; 95% CI, -5.5 to 5.0; P = 0.002 for noninferiority). Sensitivity analyses confirmed the results of the primary analyses. CONCLUSIONS: Drug-coated balloon angioplasty was superior to standard angioplasty for the treatment of stenotic lesions in dysfunctional hemodialysis arteriovenous fistulas during the 6 months after the procedure and was noninferior with respect to access circuit-related serious adverse events within 30 days. (Funded by Medtronic; IN.PACT AV Access Study ClinicalTrials.gov number, NCT03041467.).

NF-κB Decoy Oligodeoxynucleotide-Coated Balloon Catheter for Arteriovenous Fistula in Hemodialysis.

INTRODUCTION: New treatments to inhibit neointimal formation after percutaneous transluminal angioplasty (PTA) are needed for patients undergoing chronic hemodialysis (HD). We compared the efficacy and safety of AMG0102, a balloon catheter containing nuclear factor κB (NF-κB) decoy oligodeoxynucleotide (ODN) with the PTA balloon catheter (control group) for arteriovenous fistula (AVF) stenosis. METHODS: In total, 175 patients (age ≥20 years, undergoing HD, with venous stenosis at the anastomotic region) were registered in this prospective open-label, randomized study. Patients were followed postoperatively for 36 weeks. The duration of primary patency on the targeted venous stenosis site (primary endpoint) was estimated by the Kaplan-Meier method. RESULTS: A lower restenosis risk was observed for the AMG0102 group, but it was not statistically significant (stratified log-rank test P = 0.250, hazard ratio [HR] 0.774; 95% confidence interval [CI]: 0.500-1.198). The median duration of primary patency was 245 days and 172 days in the AMG0102 and control groups, respectively. After stratification based on the status of diabetes complications, the HR was 0.666 (95% CI: 0.366-1.212; P = 0.183) and the median duration of primary patency was prolonged by 108 days in the AMG0102 group with diabetes complications (245 days) compared with the control group (137 days). Adverse event (AE) incidence up to 36 postoperative weeks did not differ between groups. Four device failures occurred in 3 patients (AMG0102 group), but none resulted in AEs. CONCLUSION: Further modifications to enhance NF-κB decoy ODN uptake and efficacy are necessary to show its clinical utility for AVF stenosis in chronic HD.

2005 Japanese Society for Dialysis Therapy guidelines for vascular access construction and repair for chronic hemodialysis.

The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Dr Ohira, has published an original Japanese guideline, 'Guidelines for Vascular Access Construction and Repair for Chronic Hemodialysis'. The guideline was created mainly because of the existence of numerous factors characteristic of Japanese hemodialysis therapy, which are described in this report, and because we recognized the necessity for standardization in vascular access-related surgeries. This guideline consists of 10 chapters, each of which includes guidelines, explanations or comments and references. The first chapter discusses informed consent of vascular access (VA)-related surgeries, which often resulted in trouble between dialysis staff and patients. The second chapter describes the fundamentals of VA construction and timing of the introduction of hemodialysis with emphasis on the avoidance of catheter indwelling if at all possible. In the third chapter, arteriovenous fistula (AVF) construction and management are discussed from the viewpoint of the most preferable type of VA. The fourth chapter deals with arteriovenous grafts (AVG) which has recently increased in clinical applications. The factors which improve the AVG patency rate are discussed and postoperative management methods are emphasized to avoid possible complications. The fifth chapter deals with short and long-term vascular catheters. It is emphasized that these methods are definitely effective but, at the same time, are apt to be associated with several serious complications and might result in vascular damage. In the sixth chapter, superficialization of an artery is explained. This was originally for emergency use or backup but has been used permanently in 2-3% of Japanese hemodialysis patients. In the seventh chapter, methods for the use of VA are described and the buttonhole method is referred to as one of the options for patients who complain of intense pain at every cannulation. In the eighth chapter, the importance of continuous monitoring is stressed for maintaining appropriate function of VA. As a rule, the internal shunt type VA (AVF, AVG) places a burden on cardiac function. Thus, in the ninth chapter, it is stressed that VA construction, maintenance and repair should always be carried out with consideration of cardiac function which is not constant but variable. The 10th chapter forms one of the cores of this guideline and deals with repair and timing of VA. It is shown how to select a surgical or interventional repair method. In the final 11th chapter, VA types and resultant morbidity and mortality of hemodialysis patients are reviewed.

In preparation for a treatment guideline for suitable vascular access repair in Japan.

In cases of vascular access (VA) for hemodialysis including arteriovenous fistula and arteriovenous graft, venipuncture and hemostasis are usually repeated three times a week. Accordingly, it is assumed that VA vascular disorders are worsened following long-term hemodialysis. In particular, angiostenosis frequently occurs and results in insufficient blood flow or increased venous pressure. Additionally, stenosis is a major cause of VA occlusion. While VA intervention treatment is mainstream for VA stenosis, its major advantage lies in its less invasiveness because it is a percutaneous treatment. A further advantage of this treatment procedure is that the existing VA can be preserved intact. For practical use of VA intervention treatment, however, compliance with the therapeutic indication guideline is required. In K/DOQI of the United States, such a guideline has already been formulated based on evidence and specialist opinion, while the guideline of the European Vascular Access Society is presented in the form of a flowchart. The Japanese Society for Dialysis Therapy is currently preparing a guideline for the construction and maintenance of VA, which introduces the timing and principles of repair of VA in the following six categories: (i) stenosis; (ii) occlusion; (iii) venous hypertension; (iv) steal syndrome; (v) excess blood flow; and (vi) infection. Except for infection, most of the treatments for these events involve VA intervention, thus the need for the guideline for VA intervention treatment is becoming widely recognized.

Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous grafts: a review.

Stenosis at the graft-vein junction caused by intimal hyperplasia (IH) is the major cause of failure of vascular access grafts used for hemodialysis. There is a strong relationship between hemodynamic factors and formation of IH. The hemodynamic pattern and the location of IH are different in arterial bypass grafts (ABGs) compared with arteriovenous grafts (AVGs). In an ABG, end-to-side anastomosis of the expanded polytetrafluoroethylene graft and artery produces hemodynamic changes around the junction. IH develops at the arterial floor and the toe and heel of the distal anastomosis. Low shear stress and oscillating shear forces at the arterial floor and the heel plus a high wall sheer stress (WSS) gradient at the toe probably promote IH development. Compliance mismatch between the graft and artery causes turbulence that may contribute to IH formation. The blood flow rate in AVGs is 5-10 times greater than that in ABGs. High flow causes turbulence that injures endothelial cells and eventually results in IH. The peak WSS in AVGs is about 6 N/m(2), much higher than that in ABGs. Excessively high WSS may effect IH formation in AVGs. Several venous cuff or patch anastomotic designs have been used in attempts to regulate hemodynamic factors in grafts. In ABGs, these designs appear to help decrease IH formation. In AVGs, however, they generally have not improved patency rates. In a high-flow system such as an AVG, more drastic changes in anastomotic design may be required.

Adenovirus-mediated functional gene transfer into parathyroid cells in vivo and in vitro.

Chronic renal failure patients usually develop secondary hyperparathyroidism and, as the disease progresses, there is a decrease in the number of vitamin D and calcium-sensing receptors (CaRs) in the parathyroid glands. Parathyroid cell function can be controlled if a functional gene is transferred into these cells using an adenovirus vector. Vitamin D or CaR genes transferred by the infected adenovirus vector induced a reduction in parathyroid hormone secretion. These results suggest that adenovirus-mediated gene transfer is a useful technique for control of parathyroid cell function.