Stent Graft versus Balloon Angioplasty for Failing Dialysis-Access Grafts

original article

T h e n e w e ngl a nd j o u r na l o f m e dic i n e

n engl j med 362;6 nejm.org february 11, 2010494

Stent Graft versus Balloon Angioplasty for Failing Dialysis-Access Grafts

Ziv J. Haskal, M.D., Scott Trerotola, M.D., Bart Dolmatch, M.D., Earl Schuman, M.D., Sanford Altman, M.D., Samuel Mietling, M.D., Scott Berman, M.D., Gordon McLennan, M.D., Clayton Trimmer, D.O., John Ross, M.D.,

and Thomas Vesely, M.D.

From the University of Maryland Medical Center, Baltimore (Z.J.H.); the Hospital of the University of Pennsylvania, Philadel-phia (S.T.); the University of Texas–South-western Medical Center, Dallas (B.D., C.T.); Oregon Surgical Consultants, Port-land (E.S.); Open Access Vascular Access Center, Miami (S.A.); Vascular Access Center, Augusta, GA (S.M.); Tucson Vas-cular Surgery, Tucson, AZ (S.B.); Indiana University School of Medicine, Indianap-olis (G.M.); Bamberg County Hospital and Nursing Center, Bamberg, SC (J.R.); and the Vascular Access Center of Frontenac Grove, Frontenac, MO (T.V.). Address re-print requests to Dr. Haskal at the Divi-sion of Vascular and Interventional Radi-ology, University of Maryland Medical Center, 22 S. Greene St., GK214, Baltimore, MD 21201, or at [email protected].

N Engl J Med 2010;362:494-503.Copyright © 2010 Massachusetts Medical Society.

A bs tr ac t

Background

The leading cause of failure of a prosthetic arteriovenous hemodialysis-access graft is venous anastomotic stenosis. Balloon angioplasty, the first-line therapy, has a tendency to lead to subsequent recoil and restenosis; however, no other therapies have yet proved to be more effective. This study was designed to compare conven-tional balloon angioplasty with an expanded polytetrafluoroethylene endovascular stent graft for revision of venous anastomotic stenosis in failing hemodialysis grafts.

Methods

We conducted a prospective, multicenter trial, randomly assigning 190 patients who were undergoing hemodialysis and who had a venous anastomotic stenosis to undergo either balloon angioplasty alone or balloon angioplasty plus placement of the stent graft. Primary end points included patency of the treatment area and pat-ency of the entire vascular access circuit.

Results

At 6 months, 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). In addition, the incidence of freedom from subsequent interventions at 6 months was significantly greater in the stent-graft group than in the balloon-angioplasty group (32% vs. 16%, P = 0.03 by the log-rank test and P = 0.04 by the Wilcoxon rank-sum test). The incidence of binary restenosis at 6 months was greater in the balloon-angioplasty group than in the stent-graft group (78% vs. 28%, P<0.001). The incidences of adverse events at 6 months were equivalent in the two treatment groups, with the exception of restenosis, which occurred more frequently in the balloon-angioplasty group (P<0.001).

Conclusions

In this study, percutaneous revision of venous anastomotic stenosis in patients with a prosthetic hemodialysis graft was improved with the use of a stent graft, which appears to provide longer-term and superior patency and freedom from repeat interventions than standard balloon angioplasty. (ClinicalTrials.gov num-ber, NCT00678249.)

The New England Journal of Medicine Downloaded from nejm.org at QUEENS UNIV on October 23, 2011. For personal use only. No other uses without permission.

Copyright © 2010 Massachusetts Medical Society. All rights reserved.

Stent Gr aft vs. Balloon Angioplasty for failing Dialysis-Access Gr afts

n engl j med 362;6 nejm.org february 11, 2010 495

By 2008, more than 341,000 patients in the United States were undergoing hemo-dialysis for treatment of their end-stage

renal disease.1 The National Kidney Foundation Kidney Disease Outcomes Quality Initiative seeks to increase the use of autogenous fistulas, yet many patients continue to undergo hemodialysis with the use of prosthetic arteriovenous grafts. The reasons for this discrepancy between the recommendation and practice are multifactorial and continue to be debated.2,3 The costs of maintaining vascular access are substantial; for example, the cost of treating a patient who has failure of a hemodialysis access graft is signifi-cantly higher ($62,000 per patient-year) than the cost of treating a patient who does not have ac-cess failure.1,4

Many percutaneous techniques and endovas-cular tools have been used to treat the neointi-mal stenoses that develop at the site of venous anastomoses of arteriovenous grafts. At best, secondary patency of arteriovenous grafts (i.e., patency after an intervention) is 50% at 3 years after the creation of the vascular access; typical-ly, multiple interventions are required to main-tain patency.5,6 No reported mechanical, endovas-cular, or pharmacologic approaches have improved the patency of arteriovenous grafts as compared with balloon angioplasty alone.7-15 We hypothe-sized that revision of a venous anastomotic stenosis with a stent graft constructed with the same material as the graft would prevent elastic recoil and tissue ingrowth, thereby improving long-term patency as compared with that afford-ed by standard balloon angioplasty.

Me thods

Study Design

In our prospective, multicenter, randomized, con-trolled trial, patients were eligible if they had end-stage renal disease and were undergoing long-term hemodialysis with the use of failing, but nonthrombosed, prosthetic arteriovenous grafts. The study was designed to assess the safe-ty and efficacy of an expanded polytetrafluoro-ethylene stent graft, as compared with balloon angioplasty, for the treatment of hemodynami-cally significant venous anastomotic stenosis in an arteriovenous graft.

Inclusion and exclusion criteria, listed in Ta-ble 1, were developed in accordance with guide-

lines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative and the Soci-ety of Interventional Radiology.16-18 The study was approved by each center’s institutional review board and the Food and Drug Administration and was in compliance with Health Insurance Portability and Accountability Act regulations; all patients provided written informed consent. An independent clinical events committee at Har-vard Clinical Research Institute (Boston) adjudi-cated the clinical data and the Angiographic Core Lab of the Cardiovascular Research Foun-dation (New York) analyzed the angiographic films. The principal investigator designed the study, with assistance from the sponsor (Bard Peripheral Vascular). The data were collected by on-site investigators under the auspices of the sponsor and principal investigator for analysis; Harvard Clinical Research Institute performed the statistical analyses. The principal investigator prepared the manuscript, which was reviewed by all authors, who vouch for the accuracy and com-pleteness of the reported data.

Study End Points

The study objective was to demonstrate that treat-ment with a stent graft is not inferior to treat-ment with balloon angioplasty alone regarding the primary end point, the 6-month primary pat-ency of a stenotic venous anastomosis in the treatment area. Secondary end points included safety variables, procedural success (successful percutaneous insertion of the stent graft), pri-mary patency of the access circuit at 2 months and 6 months, the percent stenosis of the treat-ment area at 2 months and 6 months, and free-dom from subsequent intervention. See the Sup-plementary Appendix (available with the full text of this article at NEJM.org) for definitions of “treatment area” and “primary patency” and mea-sures of successful intervention.

Stent Graft

The investigational device consisted of a self-expanding nitinol stent covered in carbon-impreg-nated expanded polytetrafluoroethylene (Flair Endovascular Stent Graft, Bard Peripheral Vascu-lar). Two stent-graft configurations were used: tubular (straight) and flared. The flared configu-ration was used when the diameter of the out-flow vein beyond the stenosis was larger than that of the arteriovenous graft. The stent graft





was available in diameters of 6 to 9 mm and lengths of 30, 40, and 50 mm. It was deployed through a 9-French delivery catheter.

Randomization and Intervention

Once the enrollment criteria were met, angiogra-phy of the graft and treatment area was per-formed with the use of orthogonal magnified views, each 30 degrees or more apart, and a radio-paque 1-mm graduated ruler in the imaged field of view. The percent stenosis was calculated as follows: [1 − (minimal lumen diameter ÷ nondis-eased lumen diameter)] × 100, where the minimal lumen diameter was the narrowest lumen diam-eter within the stenosed area and the nondis-eased lumen diameter was the lumen diameter of

the nondiseased arteriovenous graft or vein just upstream of the lesion. Remote secondary lesions more than 3 cm from the treatment area were required to have been treated until the stenosis was less than 30%, before randomization.

Randomization was performed with the use of permuted blocks, identified in sealed enve-lopes that were sent to each site in advance. If the lesion met study criteria, then balloon angio-plasty was performed with the use of an appro-priately sized conventional (noncutting, noncom-pliant) angioplasty balloon. After angioplasty, patients were randomly assigned to undergo placement of a stent graft or to receive no other treatment. No patients were excluded before randomization because of resistant stenoses that

Table 1. Inclusion and Exclusion Criteria in the Study.

Inclusion criteria

Age of 18 to 90 yr and a hemodialysis access consisting of a synthetic arteriovenous access graft located in the arm.

Angiographic evidence of ≥1 stenoses, ≤7 cm in length and ≥50%, at the graft-vein anastomosis of a synthetic arterio-venous access graft, with the entire lesion located within 7 cm of the anastomosis, such that approximately 1 cm of the stent graft will be extended into a nondiseased vein and approximately 1 cm, but no more than 2 cm, of the stent graft will be extended into a nondiseased arteriovenous graft.

Clinical evidence of a hemodynamically significant stenosis.

Percutaneous endovascular therapy thought by the investigator to have been the best treatment choice for the identi-fied lesion.

Patient’s ability to provide written informed consent.

Synthetic arteriovenous access grafts implanted >30 days before enrollment and ≥1 successful hemodialysis sessions performed.

During primary balloon angioplasty, full expansion of an appropriately sized angioplasty balloon, in the operator’s judgment.

Exclusion criteria

Concomitant disease (e.g., terminal cancer) or other medical condition likely to result in death within 6 mo after the time of implantation.

Stenosis with a corresponding thrombosis treated within 7 days before enrollment.

A second lesion in the access circuit (area from the arteriovenous access graft arterial anastomosis to the superior vena cava–right atrial junction), ≤3 cm from the edges of the primary lesion, either treated within 30 days before enrollment or ≥30%.

The presence of a second lesion in the access circuit >3 cm from the edges of the primary lesion that was ≥30%. Second lesions that were ≥30% must have been treated before patient inclusion to reduce the percent stenosis to <30%.

Being unwilling or unable to return for follow-up visits or reason to believe that adherence to follow-up visits would be irregular.

A stent placed at the target lesion site.

A blood coagulation disorder or sepsis.

Requirement that the stent graft would have to cross an angle (between the inflow vein and synthetic arteriovenous access graft) of >90 degrees.

Requirement that the stent graft would have to be deployed fully across the elbow joint (which is identified radiographi-cally as a combination of the humeroulnar joint and the humeroradial joint).

A contraindication to the use of contrast medium.

Infected arteriovenous access graft.

Current or scheduled enrollment in other, conflicting studies.

Procedural use of another investigational device.

Pregnancy.





prevented full expansion of the initial angio-plasty balloon. If a patient was randomly as-signed to the stent-graft group, a device of ap-propriate length, configuration, and diameter (≤1 mm greater than the arteriovenous graft, to avoid the use of an oversized device) was chosen. The stent graft was placed and was then dilated, with a balloon diameter equal to that used in the balloon-angioplasty group. Lesions were dilated to reduce the stenosis in the treated area to less than 30%. The angiograms were later sent to the Angiographic Core Lab for analysis.

Clinical and Angiographic Follow-up Regimen

Patients were treated and discharged according to each center’s standard of care. Anticoagula-tion or antiplatelet agents were administered after the procedure at the physician’s discretion. A single, intravenous dose of prophylactic antibi-otic — usually cefazolin sodium, in patients who did not have an allergy — was administered in the stent-graft group.

Mandatory clinical evaluations and magnified quantitative angiography were performed 2 and 6 months after the index procedure, with the use of similar imaging protocols. Medical events, hospitalizations, access interventions, and adverse events were recorded. Graft function was as-sessed by means of a clinical evaluation of the same clinical or hemodynamic indicator used to assess graft function during the initial angio-graphic evaluation (one of the graft-function indi-cators accepted by the National Kidney Founda-tion Kidney Disease Outcomes Quality Initiative), as well as by means of angiographic evaluation. Catheter-based interventions were performed in patients who both met clinical criteria for graft dysfunction and had stenoses of more than 50%. In accordance with the National Kidney Founda-tion Kidney Disease Outcomes Quality Initiative guidelines, investigators were instructed not to intervene regarding asymptomatic, clinically silent (i.e., incidentally diagnosed) stenoses found in the treatment area during angiography at 2 and 6 months.

Statistical Analysis

We calculated the sample size needed to test the primary noninferiority hypothesis using the meth-ods of Blackwelder.19 The incidence of primary patency at 6 months was estimated as 60% in the stent-graft group and 50% in the balloon-angio-

plasty group. The two rates were considered clin-ically noninferior if the difference was 10 per-centage points or less (with a significance threshold of P = 0.05 on a one-tailed test and 80% statistical power). On this basis, the number of patients required for each of the two treatment groups was calculated to be 76. The target num-ber of patients enrolled in each group was set at 95, to account for a dropout rate of up to 20%. Thus, the total target sample size was 190 pa-tients.

Intention-to-treat analyses were performed to evaluate the 6-month primary patency. The times to the return of symptoms and patency were analyzed with the use of Kaplan–Meier product–limit survival estimates. The data for patients with missed 6-month visits were censored in the estimation of the percentage of patients with graft patency at 6 months.

Continuous secondary variables (e.g., percent stenosis) were analyzed by means of parametric or nonparametric analysis of variance with cova-riate adjustment. Outcomes for nonprimary ef-fectiveness variables (e.g., primary patency of the access circuit) were analyzed at 2 and 6 months after the procedure. Subgroup analyses were performed to evaluate the influence of concomi-tant variables. P values less than 0.05 were con-sidered to indicate statistical significance.

R esult s

Patients

A total of 190 patients at 13 study sites were en-rolled: 97 were randomly assigned to undergo implantation of the investigational stent graft and 93 were randomly assigned to undergo the control procedure, balloon angioplasty, only. The study patients consisted of 69 men and 121 wom-en (Table 2). Participating centers were academic, community-based, inpatient, or freestanding out-patient dialysis centers. There were no signifi-cant differences between the two treatment groups at baseline with respect to demographic charac-teristics, relevant medical history, or characteris-tics of the arteriovenous access graft, with the exception of a higher incidence of axillary venous anastomosis in the balloon-angioplasty group. Nor were there significant differences between the two groups with respect to the nature or prevalence of abnormalities leading to the inter-vention in the arteriovenous access graft. The





Table 2. Characteristics of the Study Patients and Access Grafts at Baseline, According to Treatment Group.*

CharacteristicStent Graft

(N = 97)Balloon Angioplasty

(N = 93) P Value

Age — yr 61.8±14.6 59.8±13.6 0.33

Male sex — no./total no. (%) 33/97 (34) 36/93 (39) 0.55

Hypertension — no./total no. (%) 96/97 (99) 87/93 (94) 0.06

Coronary artery disease — no./total no. (%) 33/90 (37) 34/88 (39) 0.88

Congestive heart failure — no./total no. (%) 25/89 (28) 19/86 (22) 0.39

Diabetes — no./total no. (%) 59/97 (61) 58/93 (62) 0.88

Chronic obstructive pulmonary disease — no./total no. (%) 7/91 (8) 5/87 (6) 0.77

Hypercoagulability — no./total no. (%) 1/91 (1) 0/83 1.00

Glomerulonephritis — no./total no. (%) 5/90 (6) 3/84 (4) 0.72

Anticoagulant agents — no./total no. (%) 40/97 (41) 36/93 (39) 0.77

Antiplatelet agents — no./total no. (%) 11/97 (11) 6/93 (6) 0.31

Age at placement of arteriovenous graft — yr 2.19±1.89 2.65±2.14 0.13

Location of arteriovenous graft — no./total no. (%)†

Right arm 23/97 (24) 22/93 (24) 0.99

Left arm 74/97 (76) 71/93 (76)

Forearm 20/97 (21) 24/92 (26) 0.64

Upper arm 73/97 (75) 67/92 (73)

Across elbow joint (forearm with jump graft) 2/97 (2) 1/92 (1)

Forearm and elbow 2/97 (2) 0/92

Configuration of graft — no./total no. (%) 0.62

Looped 42/97 (43) 37/93 (40)

Straight 55/97 (57) 56/93 (60)

Arterial anastomosis — no./total no. (%) 0.28

Axillary 2/97 (2) 2/93 (2)

Brachial 92/97 (95) 87/93 (94)

Radial 1/97 (1) 4/93 (4)

Ulnar 0/97 0/93

Other 2/97 (2) 0/93

Venous anastomosis — no./total no. (%) 0.009

Axillary 22/97 (23) 30/93 (32)

Basilic 56/97 (58) 51/93 (55)

Brachial 14/97 (14) 3/93 (3)

Cephalic 3/97 (3) 9/93 (10)

Other 2/97 (2) 0/93

Previous access — no./total no. (%)†

Arteriovenous access graft 55/94 (59) 50/90 (56) 0.77

Venous anastomosis 64/94 (68) 60/89 (67) 1.00

Venous outflow tract 40/90 (44) 29/86 (34) 0.17

Type of arteriovenous access graft — no./total no. (%) 0.34

Tapered 14/80 (18) 10/77 (13) 0.51

Straight 53/80 (66) 61/77 (79) 0.08

Stepped 8/80 (10) 5/77 (6) 0.57

Other 5/80 (6) 1/77 (1) 0.21





three most common triggers for intervention were clinical variables, elevated venous pressure during dialysis, and detection of decreased blood flow.

Baseline Angiographic Characteristics of the Lesion

There were no significant differences between the two treatment groups with respect to angio-graphic characteristics of the target lesion: inter-polated reference-vessel diameter, minimum lu-men diameter, or percent stenosis (Table 2). The average balloon diameters during dilation were

similar in the stent-graft group and the balloon-angioplasty group. The percentage of patients with secondary lesions in the access circuit was similar in the two groups: 39% of patients receiv-ing a stent graft and 41% undergoing balloon angioplasty.

Implantation of Stent Grafts

A total of 125 stent grafts were implanted in 97 patients; 67% of the stent grafts were flared, 16% were straight, and 17% consisted of overlapping straight and flared grafts. Seventy-three patients

Table 2. (Continued.)

CharacteristicStent Graft

(N = 97)Balloon Angioplasty

(N = 93) P Value

Graft diameter — no./total no. (%)‡ 0.37

5 mm 0/81 0/80

6 mm 54/81 (67) 55/80 (69) 0.87

7 mm 5/81 (6) 7/80 (9) 0.57

8 mm 0/81 2/80 (2) 0.25

4 mm/7 mm 17/81 (21) 16/80 (20) 1.00

5 mm/8 mm 1/81 (1) 0/80 1.00

3 mm/6 mm 0/81 0/80

4.5 mm/6.5 mm 1/81 (1) 0/80 1.00

Other 3/81 (4) 0/80 0.25

Clinical sign of graft dysfunction — no./total no. (%)§ 31/97 (32) 39/93 (42) 0.17

Elevated venous pressure during dialysis — no./total no. (%) 25/97 (26) 35/93 (38) 0.08

Detection of decreased blood flow — no./total no. (%) 24/97 (25) 17/93 (18) 0.30

Abnormal flow on Doppler ultrasonography — no./total no. (%) 16/97 (16) 15/93 (16) 1.00

Angiographic data

Target lesion length 0.21

No. with data 95 90

Mean (±SD) length — mm 35.3±13.9 37.8±12.7

Interpolated reference-vessel diameter 0.07

No. with data 96 90

Mean (±SD) diameter — mm 8.3±1.5 8.7±1.7

Mean lesion diameter 0.66

No. with data 96 90

Mean (±SD) diameter — mm 2.37±0.88 2.32±0.80

Target lesion preprocedure stenosis 0.17

No. with data 96 90

Mean (±SD) % stenosis 70.9±10.5 72.9±9.0

* Plus–minus values are means ±SD.† Patients could have had a graft at more than one location and more than one previous procedure.‡ Graft diameters separated by a slash represent the diameter at each end of a tapered graft.§ Clinical signs of graft dysfunction were defined as prolonged bleeding after needle withdrawal or altered pulse or thrill in graft.





(75%) received a single device. Stent grafts were overlapped when lesion lengths (including a non-diseased 10-mm “landing zone” between the ar-teriovenous graft and outflow vein) exceeded the

longest available stent-graft length (50 mm). De-vice deployment was successful in 96 of the 97 patients (99%). A 30-mm stent graft was placed in 28% of the patients, a 40-mm graft in 36%, and a 50-mm graft in 36%.

Follow-up of the Patients

There were no significant differences between the two treatment groups regarding the atten-dance of patients at follow-up examinations at any study interval. Thirteen patients (6 of the 97 patients [6%] receiving a stent graft and 7 of the 93 patients [8%] undergoing balloon angioplasty) missed either the 2-month or 6-month follow-up evaluation: 2 patients (1 in each group) missed the 2-month follow-up visit and 11 (5 in the stent-graft group and 6 in the balloon-angioplasty group) missed the 6-month follow-up visit. A to-tal of 94% of patients in the stent-graft group and 93% of patients in the balloon-angioplasty group completed the 6-month follow-up visit.

Study End Points

On the basis of an intention-to-treat analysis, at 6 months, the incidence of primary patency of the treatment area was significantly greater in the stent-graft group (51%) than in the balloon-angioplasty group (23%) (P<0.001), as was the incidence of primary patency of the access circuit (38% vs. 20%, P = 0.008) (Table 3). Forty-five pa-tients in the stent-graft group and 66 patients in the balloon-angioplasty group had loss of pri-mary patency of the treatment area, owing to one or more of the following events: reintervention in the treatment area, thrombotic occlusion, surgi-cal intervention that excluded the treatment area from the access circuit, and abandonment of the graft because of an inability to treat the primary lesions (Table 4). At 6 months, the percentage of patients with freedom from loss of primary pat-ency of the treatment area was significantly greater in the stent-graft group than in the bal-loon-angioplasty group (P = 0.003 by the log-rank test and P = 0.008 by the Wilcoxon rank-sum test), as was the percentage with freedom from loss of primary patency of the access circuit (P = 0.03 by the log-rank test and P = 0.04 by the Wilcoxon rank-sum test) (Fig. 1). At 210 days, the stent-graft group showed superior freedom from sub-sequent interventions as compared with the bal-loon-angioplasty group (P = 0.03 by the log-rank test and P = 0.04 by the Wilcoxon rank-sum test).

Table 3. Treatment Success and Patency End Points in the Intention-to-Treat Population, According to Treatment Group.*

End Point Stent GraftBalloon

Angioplasty P Value

no. of patients/total no. (%)

Anatomical success 91/97 (94) 68/93 (73) <0.001

Hemodynamic success 97/97 (100) 93/93 (100)

Clinical success 85/97 (88) 78/93 (84) 0.49

Procedural success 91/97 (94) 68/93 (73) <0.001

Primary patency of treatment area

2 mo 77/96 (80) 71/92 (77) 0.72

6 mo 46/91 (51) 20/86 (23) <0.001

Primary patency of access circuit

2 mo 76/96 (79) 71/92 (77) 0.86

6 mo 35/92 (38) 17/86 (20) 0.008

* Definitions of treatment success are listed in the Supplementary Appendix.

Table 4. Adverse Events at 6 Months, According to Treatment Group.*

Adverse Event Stent GraftBalloon

Angioplasty P Value

no. of patients/total no. (%)

Infection 6/95 (6) 2/90 (2) 0.28

Thrombotic occlusion 31/95 (33) 19/90 (21) 0.10

Restenosis 38/95 (40) 69/90 (77) <0.001

Pseudoaneurysm 5/95 (5) 2/90 (2) 0.45

Vessel rupture 3/95 (3) 1/90 (1) 0.62

Hemorrhage 0/95 0/90

Hematoma 2/95 (2) 0/90 0.498

Edema of arm or hand 3/95 (3) 2/90 (2) 1.00

Vascular insufficiency from graft

2/95 (2) 1/90 (1) 1.00

Congestive heart failure 4/95 (4) 2/90 (2) 0.68

Cerebrovascular accident 2/95 (2) 3/90 (3) 0.68

Death 5/95 (5) 5/90 (6) 1.00

Embolism 0/95 0/90

Problems with device

Kinking 0/95 NA

Migration 4/95 (4) NA

Permanent deformation 1/95 (1) NA

* NA denotes not applicable.





These findings supported both the primary and secondary study hypotheses: the noninferiority to and superiority of the stent graft as compared with balloon angioplasty.

Procedural Success and Restenosis

The rate of procedural success was significantly higher in the stent-graft group than in the percu-taneous-transluminal-angioplasty group, with suc-cess in 94% versus 73% of patients (P<0.001) (Table 4). At 6 months, the minimum lumen di-ameter of the treatment area was, on average (mean ±SD), significantly greater with the stent graft than with balloon angioplasty alone: 5.1±1.5 mm vs. 3.3±1.5 mm (P<0.001).

The average percent stenosis was lower in the stent-graft group (32.1±19.8%) than in the balloon-angioplasty group (59.2±19.6%) (P<0.001). At 6 months, the incidence of binary restenosis (stenosis of >50% diameter) was significantly greater in the balloon-angioplasty group (78%) than in the stent-graft group (28%) (P<0.001). Restenotic lesions were, on average, significant-ly shorter in the stent graft group (18.0±12.5 mm) than in the balloon-angioplasty group (32.1±14.3 mm) (P<0.001).

At 6 months, the presence or absence of re-mote secondary lesions that were required to have been treated before study enrollment did not negate the patency advantage of the stent graft over balloon angioplasty. The incidence of pat-ency of the treatment area was greater, among patients who had secondary lesions, in the stent-graft group (44%) than in the balloon-angioplasty group (17%) (P = 0.02), as well as among patients who did not have secondary lesions (54% vs. 28%) (P = 0.006).

Logistic-regression analysis of clinical vari-ables at 6 months failed to identify any distin-guishing or significant criteria affecting primary patency — including diabetes, age, sex, history of hypercoagulability or glomerulonephritis, graft site, hypertension, or use of anticoagulation or antiplatelet therapy. By means of multiple logis-tic-regression analysis, the only criterion that was associated with primary patency at 6 months of follow-up was assignment to the stent-graft group (P<0.001).

Safety and Adverse Events

There was no significant difference in the inci-dence of reported adverse events between the

balloon-angioplasty control group and the stent-graft group, except for the incidence of restenosis, which was higher with balloon angioplasty (77%, vs. 40% with stent graft; P<0.001) (Table 4).

Discussion

Despite nearly universal agreement that native fistulas should be the hemodialysis access of first choice, prosthetic grafts continue to play an im-portant role in the creation of permanent hemo-dialysis-access circuits in patients in the United States. Though the percentage of patients under-going dialysis through prosthetic grafts may con-tinue to fall, the total number of patients with end-stage renal disease continues to grow each year.1,3 Thus, hemodialysis grafts are likely to re-main important vascular accesses, as “planned bridges” to native fistulas or in patients in whom fistulas have failed or cannot be created.17,20-22

4 col22p3

Prim

ary

Pate

ncy

ofTr

eatm

ent A

rea

(%)

100

80

60

40

20

00 30 60 90 120 150 180 210

Days after Initial Procedure

A

Stent graft

P=0.003

P=0.03

Balloon angioplasty

Balloon angioplasty

AUTHOR:

FIGURE:

RETAKE:

SIZE

4-C H/TLine Combo

Revised

AUTHOR, PLEASE NOTE: Figure has been redrawn and type has been reset.

Please check carefully.

1st2nd

3rd

Haskal

1 of 1

ARTIST:

TYPE:

MRL

2-11-10JOB: 361xx ISSUE:

Prim

ary

Pate

ncy

ofA

cces

s C

ircu

it (%

)

100

80

60

40

20

00 30 60 90 120 150 180 210

Days after Initial Procedure

B

Stent graft

Figure 1. Estimated Percentages of Patients with Primary Patency during the Study Period, According to Treatment Group.

Panel A shows the percentages with primary patency of the treatment area, and Panel B, percentages with primary patency of the access circuit. The P values shown were calculated with the use of the log-rank test.





Balloon angioplasty for stenotic arteriovenous grafts has limitations, however: the long-term durability of balloon angioplasty is limited6,9,10 and may necessitate repeated invasive proce-dures9-11 with attendant complications and costs. From 16 to 25% of hospital admissions of pa-tients with end-stage renal disease in the United States are necessitated by complications related to a vascular access; the associated costs have been estimated at nearly 1 billion dollars per year.1,4 Furthermore, the outpatient costs for pa-tients with graft failure more than doubled be-tween 1991 and 2005.1

Multiple devices and approaches for treating arteriovenous graft–related stenosis have been used and reported on in retrospective series and prospective, randomized trials. To date, none have shown any benefit over balloon angioplasty. These techniques have included angioplasty with cutting or with ultrahigh-pressure balloons, brachytherapy, cryoplasty, anticoagulation thera-py, placement of bare-metal stents, modified surgical techniques and graft configurations, and other pharmacologic approaches. Although preliminary research in minimizing the hyper-plastic process at the time of graft creation by means of pharmacologic, cellular, or gene thera-pies appears promising, such efforts are in the early stages of evaluation or development.7-15,23-29

The polytetrafluoroethylene self-expanding stent graft is a less-invasive endovascular ap-proach for revision of failing prosthetic arterio-venous grafts that is intended to mimic open surgical revision of a graft. Unlike surgery, a per-cutaneous approach optimally allows for imme-diate use of the graft, which might obviate the need for interim catheter dialysis and its associ-ated costs, risks of bloodstream infection, and other complications. The stent graft used in the present trial was designed to prevent both the elastic recoil that occurs after balloon angio-plasty, thus sustaining the short-term gain in luminal patency — an effect similar to that of uncovered (bare-metal) stents used in the access circuit — and the late loss in luminal patency due to trans-stent growth of neointimal tissue.13,28,29 The present endovascular approach also essen-tially converts the initial surgical end-to-side ve-nous anastomosis into an end-to-end anastomo-sis, providing more laminar in-line flow and

thus potentially reducing the turbulence and shear stress that contribute to the development of venous outflow stenosis.7,8,32-36

Our study involved detailed assessments and definitions of patency. All patients underwent formal angiography at 2 and 6 months, regard-less of the clinical graft function, allowing for uniform assessment of stenosis at the Angio-graphic Core Lab. The angiographic findings were an integral part of the study definition of patency. In contrast, most published studies have used the absence of clinical dysfunction alone as the measure of treatment success.7-15,25-29 The definitions used in our randomized, controlled study may provide a more accurate measure of ac-tual arteriovenous graft patency than previous retrospective studies of arteriovenous grafts. Pro-spective reports of the patency of autogenous fis-tulas have noted similar findings: the incidence of patency is lower when prospectively assessed than when retrospectively ascertained.20,37,38

In conclusion, our data indicate that the ex-panded polytetrafluoroethylene self-expanding stent graft used in the present study is superior to balloon angioplasty for the treatment of arte-riovenous access grafts that have venous anasto-motic stenosis. As compared with balloon an-gioplasty, the stent graft was associated with graft function for a longer period before subse-quent intervention and a graft lumen that had a greater diameter and had patency for a longer period.

Supported by Bard Peripheral Vascular.Dr. Haskal reports receiving consulting fees from W.L. Gore

and Associates and lecture fees from Bard Peripheral Vascular and holding stock in AngioDynamics; Dr. Trerotola, receiving consulting fees from W.L. Gore and Associates and Bard Periph-eral Vascular; Dr. Dolmatch, receiving consulting and lecture fees from Bard Peripheral Vascular and royalties for the Flair Endovascular Stent Graft and serving as an expert witness for testimony concerning the healing characteristics of the Flair Endovascular Stent Graft; Drs. Schuman and Berman, receiving consulting and lecture fees from Bard Peripheral Vascular; Dr. Altman, receiving consulting fees from Bard Peripheral Vascu-lar; Dr. McLennan, receiving consulting fees from Medtronic, Cook, and Bard Peripheral Vascular and grant support from Cook, Boston Scientific, Guerbet, and Medical International Research; Dr. Ross, receiving lecture fees from W.L. Gore and Associates, Hemosphere, Bard Peripheral Vascular, and Medrad Interventional–Possis; and Dr. Vesely, receiving consulting fees from AngioDynamics, Elcam Medical, Spire Biomedical, and W.L. Gore and Associates and lecture fees from AngioDynamics and W.L. Gore and Associates.

No other potential conflict of interest relevant to this article was reported.





References

U.S. Renal Data System. USRDS 2009 1. annual data report: atlas of chronic kid-ney disease and end-stage renal disease in the United States. Bethesda, MD: Nation-al Institute of Diabetes and Digestive and Kidney Diseases, 2009.

Vascular Access Work Group. Clinical 2. practice guidelines for vascular access. Am J Kidney Dis 2006;48:Suppl 1:S248-S273.

Chan MR, Sanchez RJ, Young HN, 3. Yevzlin AS. Vascular access outcomes in the elderly hemodialysis population: a USRDS study. Semin Dial 2007;20:606-10.

The economic cost of ESRD, vascular 4. access procedures, and Medicare spend-ing for alternative modalities of treat-ment. Am J Kidney Dis 1997;30:Suppl 1: S160-S177.

Schwab SJ, Harrington JT, Singh A, et 5. al. Vascular access for hemodialysis. Kid-ney Int 1999;55:2078-90.

NKF-DOQI clinical practice guide-6. lines for vascular access: National Kidney Foundation-Dialysis Outcomes Quality Ini-tiative. Am J Kidney Dis 1997;30:Suppl 3: S150-S191.

Fillinger MF, Reinitz ER, Schwartz 7. RA, Resetarits DE, Paskanik AM, Breden-berg CE. Beneficial effects of banding on venous intimal-medial hyperplasia in ar-teriovenous loop grafts. Am J Surg 1989; 158:87-94.

Fillinger MF, Reinitz ER, Schwartz RA, 8. et al. Graft geometry and venous intimal-medial hyperplasia in arteriovenous loop grafts. J Vasc Surg 1990;11:556-66.

Kanterman RY, Vesely TM, Pilgram 9. TK, Guy BW, Windus DW, Picus D. Dialy-sis access grafts: anatomic location of venous stenosis and results of angio-plasty. Radiology 1995;195:135-9. [Erra-tum, Radiology 1995;196:582.]

Lilly RZ, Carlton D, Barker J, et al. 10. Predictors of arteriovenous graft patency after radiologic intervention in hemodi-alysis patients. Am J Kidney Dis 2001;37: 945-53.

Lumsden AB, MacDonald MJ, Kikeri 11. D, Cotsonis GA, Harker LA, Martin LG. Prophylactic balloon angioplasty fails to prolong the patency of expanded poly-tetraf luoroethylene arteriovenous grafts: results of a prospective randomized study. J Vasc Surg 1997;26:382-90.

Misra S, Bonan R, Pflederer T, Roy-12. Chaudhury P. BRAVO I: a pilot study of vascular brachytherapy in polytetrafluo-roethylene dialysis access grafts. Kidney Int 2006;70:2006-13.

Patel RI, Peck SH, Cooper SG, et al. 13.

Patency of Wallstents placed across the venous anastomosis of hemodialysis grafts after percutaneous recanalization. Radi-ology 1998;209:365-70.

Rifkin BS, Brewster UC, Aruny JE, 14. Perazella MA. Percutaneous balloon cryo-plasty: a new therapy for rapidly recurrent anastomotic venous stenoses of hemodi-alysis grafts? Am J Kidney Dis 2005; 45(2):e27-e32.

Sun S, Beitler JJ, Ohki T, et al. Inhibi-15. tory effect of brachytherapy on intimal hyperplasia in arteriovenous fistula. J Surg Res 2003;115:200-8.

Aruny JE, Lewis CA, Cardella JF, et al. 16. Quality improvement guidelines for per-cutaneous management of the throm-bosed or dysfunctional dialysis access. J Vasc Interv Radiol 2003;14:S247-S253.

Clinical practice guidelines and for 17. vascular access. Am J Kidney Dis 2006;48: Suppl 1:S176-S247.

Gray RJ, Sacks D, Martin LG, Trero-18. tola SO. Reporting standards for percuta-neous interventions in dialysis access. J Vasc Interv Radiol 2003;14:S433-S442.

Blackwelder WC. “Proving the null 19. hypothesis” in clinical trials. Control Clin Trials 1982;3:345-53.

Biuckians A, Scott EC, Meier GH, Pan-20. neton JM, Glickman MH. The natural his-tory of autologous fistulas as first-time dialysis access in the KDOQI era. J Vasc Surg 2008;47:415-21.

Stevenson KB, Hannah EL, Lowder 21. CA, et al. Epidemiology of hemodialysis vascular access infections from longitudi-nal infection surveillance data: predicting the impact of NKF-DOQI clinical practice guidelines for vascular access. Am J Kid-ney Dis 2002;39:549-55.

NKF-K/DOQI clinical practice guide-22. lines for vascular access: update 2000. Am J Kidney Dis 2001;37:Suppl 1:S137-S181.

Luo Z, Akita GY, Date T, et al. Adeno-23. virus-mediated expression of beta-adren-ergic receptor kinase C-terminus reduces intimal hyperplasia and luminal stenosis of arteriovenous polytetrafluoroethylene grafts in pigs. Circulation 2005;111:1679-84.

Kohler TR, Toleikis PM, Gravett DM, 24. Avelar RL. Inhibition of neointimal hyper-plasia in a sheep model of dialysis access failure with the bioabsorbable Vascular Wrap paclitaxel-eluting mesh. J Vasc Surg 2007;45:1029-37.

Konner K. Paclitaxel — a tool to pre-25. vent stenosis in vascular access for haemo-dialysis? Blood Purif 2006;24:287-8.

Yevzlin AS, Conley EL, Sanchez RJ, 26. Young HN, Becker BN. Vascular access outcomes and medication use: a USRDS study. Semin Dial 2006;19:535-9.

Rajan DK, Platzker T, Lok CE, et al. 27. Ultrahigh-pressure versus high-pressure angioplasty for treatment of venous anas-tomotic stenosis in hemodialysis grafts: is there a difference in patency? J Vasc In-terv Radiol 2007;18:709-14.

Hoffer EK, Sultan S, Herskowitz MM, 28. Daniels ID, Sclafani SJ. Prospective ran-domized trial of a metallic intravascular stent in hemodialysis graft maintenance. J Vasc Interv Radiol 1997;8:965-73.

Vogel PM, Parise C. SMART stent for 29. salvage of hemodialysis access grafts. J Vasc Interv Radiol 2004;15:1051-60.

Guiu B, Loffroy R, Ben Salem D, et al. 30. Angioplasty of long venous stenoses in hemodialysis access: at last an indication for cutting balloon? J Vasc Interv Radiol 2007;18:994-1000.

Vesely TM, Siegel JB. Use of peripheral 31. cutting balloon to treat hemodialysis-re-lated stenoses. J Vasc Interv Radiol 2005; 16:1593-603.

Roy-Chaudhury P, Kelly BS, Miller 32. MA, et al. Venous neointimal hyperplasia in polytetrafluoroethylene dialysis grafts. Kidney Int 2001;59:2325-34.

Sottiurai VS, Yao JS, Batson RC, Sue 33. SL, Jones R, Nakamura YA. Distal anasto-motic intimal hyperplasia: histopatho-logic character and biogenesis. Ann Vasc Surg 1989;3:26-33.

Longest PW, Kleinstreuer C. Numeri-34. cal simulation of wall shear stress condi-tions and platelet localization in realistic end-to-side arterial anastomoses. J Bio-mech Eng 2003;125:671-81.

Krueger U, Zanow J, Scholz H. Com-35. putational fluid dynamics and vascular access. Artif Organs 2002;26:571-5.

Fillinger MF, Kerns DB, Bruch D, Re-36. initz ER, Schwartz RA. Does the end-to-end venous anastomosis offer a functional advantage over the end-to-side venous anastomosis in high-output arteriovenous grafts? J Vasc Surg 1990;12:676-90.

Huijbregts HJ, Bots ML, Wittens CH, 37. Schrama YC, Moll FL, Blankestijn PJ. He-modialysis arteriovenous fistula patency revisited: results of a prospective, multi-center initiative. Clin J Am Soc Nephrol 2008;3:714-9.

Dixon BS, Beck GJ, Vazquez MA, et al. 38. Effect of dipyridamole plus aspirin on he-modialysis graft patency. N Engl J Med 2009;360:2191-201.Copyright © 2010 Massachusetts Medical Society.



Stent Graft versus Balloon Angioplasty for Failing Dialysis-Access Grafts

Documents