The n e w e ng l a n d j o u r na l of m e dic i n e

5. Liese AD, DAgostino RB Jr, Hamman RF, et al. The burden of cardiovascular disease risk factors according to body mass index
diabetes mellitus among US youth: prevalence estimates from the
SEARCH for Diabetes in Youth Study. Pediatrics 2006;118:1510-8.
6. Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett
PH, Looker HC. Childhood obesity, other cardiovascular risk
factors, and premature death. N Engl J Med 2010;362:485-93.
7. Li C, Ford ES, Zhao G, Mokdad AH. Prevalence of pre-diabe-
tes and its association with clustering of cardiometabolic risk
factors and hyperinsulinemia among U.S. adolescents: National
Health and Nutrition Examination Survey 2005-2006. Diabetes
Care 2009;32:342-7.
8. Morrison JA, Glueck CJ, Horn PS, Wang P. Childhood predic-
tors of adult type 2 diabetes at 9- and 26-year follow-ups. Arch
Pediatr Adolesc Med 2010;164:53-60.
9. Minino AM, Arias E, Kochanek KD, Murphy SL, Smith BL.
Deaths: final data for 2000. Natl Vital Stat Rep 2002;50:1-119.
10. Gregg EW, Cheng YJ, Cadwell BL, et al. Secular trends in
in US adults. JAMA 2005;293:1868-74.
11. Lipscombe LL, Hux JE. Trends in diabetes prevalence, inci-
dence, and mortality in Ontario, Canada 1995-2005: a popula-
tion-based study. Lancet 2007;369:750-6.
12. Gerstein HC, Santaguida P, Raina P, et al. Annual incidence
and relative risk of diabetes in people with various categories of
dysglycemia: a systematic overview and meta-analysis of pro-
spective studies. Diabetes Res Clin Pract 2007;78:305-12.
13. Hirst K, Baranowski T, DeBar L, et al. HEALTHY study ra-
tionale, design and methods: moderating risk of type 2 diabetes
in multi-ethnic middle school students. Int J Obes (Lond)
2009;33:Suppl 4:S4-S20.
14. Murray CJ, Kulkarni SC, Michaud C, et al. Eight Americas:
investigating mortality disparities across races, counties, and
race-counties in the United States. PLoS Med 2006;3(9):e260.
Copyright 2010 Massachusetts Medical Society.

Fistula First, Stent Graft Second

Robert K. Kerlan, Jr., M.D., and Jeanne M. LaBerge, M.D.

A growing number of patients in the United States
undergo efficient hemodialysis through autoge-
nous arteriovenous fistulas or prosthetic arterio-
venous grafts. Unfortunately, these vascular con-
duits are fraught with complications, and failing
access remains the leading cause of hospitaliza-
tion for patients undergoing dialysis.1
The superiority of autogenous arteriovenous
fistulas as compared with prosthetic arteriovenous
grafts is well established. Fistulas have a far
lower risk of failure and a reduced requirement
for revision as compared with prosthetic grafts.
In 1997, the National Kidney Foundation Kidney
Disease Outcomes Quality Initiative recommended
a goal of arteriovenous fistula formation in 50%
of all new patients undergoing hemodialysis. In
2005, the Center for Medicare and Medicaid Ser-
vices raised the target to 66% in the breakthrough
initiative that has become known as Fistula
First.2
Unfortunately, a substantial number of patients
lack suitable veins for the creation of autogenous
fistulas and require placement of prosthetic grafts.
The high rate of graft failure in such patients
leads to increased cost of treatment and periodic
loss of access. Ameliorating the problem of graft
stenosis has been the subject of intense investi-
gation over the past decade. The study by Haskal
and colleagues in this issue of the Journal3 provides
hope that, as we enter the new decade, patients
with arteriovenous grafts may experience a bright-
er future.
The major cause of failure of prosthetic arterio-
venous grafts is stenosis at the venous anastomo-
sis of the graft. Attempts to prevent or reduce the
incidence of this problem through surgical or
pharmacologic means have been largely unpro-
ductive. In a recent report in the Journal, pharma-
cologic treatment with dipyridamole and aspirin
resulted in only a small (5-percentage-point) dif-
ference in restenosis as compared with placebo.4
Balloon angioplasty has been the standard
treatment for stenosis of a venous anastomotic
graft. Yet the benefit of angioplasty is offset by
a high rate of restenosis within weeks or a few
months after the procedure. To date, randomized,
controlled trials have not shown a substantial pro-
longation of graft patency after angioplasty, find-
ings that have led to controversy regarding the
merit of surveillance and early intervention.5
A variety of innovative percutaneous techniques
have been used to treat anastomotic graft stenos-
es, such as cutting balloons, cryoballoons, and
bare-metal stents. None of these interventions
have significantly prolonged graft patency as com-
pared with conventional balloon angioplasty in
appropriately sized, prospective, randomized, con-
trolled trials.6,7
The study by Haskal et al. appears to be the
first large, randomized, controlled trial to clearly
demonstrate superiority of an approach over bal-
loon angioplasty. Their data reveal that treating
a venous outflow stenosis with a stent graft more
than doubles the rate of graft patency, and sub-

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The New England Journal of Medicine

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 editorials
stantially reduces the need for reintervention, as
compared with angioplasty. Although patients
who presented with graft occlusion were not en-
rolled in the study, it is logical to infer that stent
grafts would have a similar patency advantage
when a venous outflow stenosis is identified after
removal of the thrombus.
Despite the improved outcomes demonstrated
by Haskal et al., stent grafts do not represent a
panacea for patients with failing arteriovenous
grafts. Six months after stent-graft placement, pri-
mary dialysis-access patency was achieved in only
half the patients. A pessimist might conclude that
performance of the arteriovenous graft can be im-
proved from dismal (with angioplasty) to merely
poor (with stent grafts). Indeed, both angioplasty
and stent grafts are imperfect treatments, and
even with this new technological innovation, there
is much room for improvement.
Several other details in the study by Haskal
et al. may temper enthusiasm for the immediate
adoption of stent grafts as the treatment of choice
for anastomotic arteriovenous graft stenosis. First,
there was a trend toward a higher rate of throm-
botic occlusion in the stent-graft group (33%) than
in the balloon-angioplasty group (21%) (P=0.10).
This raises the possibility that adjunctive system-
ic anticoagulant or antiplatelet therapy may yield
additional benefit. A study of a stent graft bonded
with heparin is currently under investigation.8
Second, the relatively short follow-up period in
the study by Haskal et al. limits our understand-
ing of the true clinical value of stent-graft revi-
sion in arteriovenous grafts. Though patency was
improved at 6 months, the longer-term outcomes
are unknown. In the current health care environ-
ment, the financial effect of stent-graft therapy
must be considered. Will sufficient improvement
in arteriovenous graft patency at 2 to 3 years be
observed, and will it offset the increased cost of
stent-graft placement?
Finally, the study was powered to show non-
inferiority, and the sample size was relatively small
(190 patients). Although this clinical trial was well
designed, with careful assessment of venographic
and clinical end points, it will be important to
confirm the study findings in subsequent inves-
tigations.
The ultimate goal in hemodialysis management
is to provide each patient with a vascular access
that will last a lifetime. With widespread adoption
n engl j med 362;6 nejm.org february 11, 2010
The New England Journal of Medicine
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Copyright 2010 Massachusetts Medical Society. All rights reserved.
of the Fistula First initiative, we are coming
closer to realizing this goal. The most pressing
problems in the coming decade will lie not in
managing arteriovenous graft failure but in pre-
venting, detecting, and treating arteriovenous-fis-
tula dysfunction.
One hopes that the beneficial effects of stent
grafts reported by Haskal et al. will also be
observed in patients with autogenous-fistula
stenoses. Preliminary data are promising and sug-
gest an advantage of stent grafts over angioplasty
or bare-metal stents.9 Perhaps more importantly,
there is hope that stent grafts can be used to treat
central venous stenosis effectively. Balloon angio-
plasty and bare-metal stents have yielded extreme-
ly disappointing results in this anatomical loca-
tion, with incidences of primary patency at 1 year
of 29% and 21%, respectively.10 A durable solution
to the problem of central venous stenosis would be
an extraordinary advance in the care of patients
undergoing dialysis.
In conclusion, the use of stent grafts to treat
dysfunctional arteriovenous grafts is an important
advance that will most likely change the practice
of percutaneous intervention and provide imme-
diate benefit to the many patients suffering from
graft dysfunction. If the findings of Haskal et al.
are confirmed, the strategy for dialysis-access
planning in the coming decade may change from
Fistula First to fistula first, arteriovenous graft
with stent-graft revision second.
Financial and other disclosures provided by the authors are
available with the full text of this article at NEJM.org.
From the University of California, San Francisco, San Francisco.
1. United States Renal Data System. USRDS 2009 annual data
report: atlas of end-stage renal disease in the United States.
Bethesda, MD: National Institute of Health, National Institute of
Diabetes and Digestive Diseases, 2009. (Accessed January 21, 2010,
at http://www.usrds.org/2009/slides/indiv/INDEX_ESRD.HTML.)
2. Vascular Access Work Group. Clinical practice guidelines for
vascular access. Am J Kidney Dis 2006;48:Suppl 1:S248-S273.
3. Haskal ZJ, Trerotola S, Dolmatch B, et al. Stent graft versus
balloon angioplasty for failing dialysis-access grafts. N Engl J
Med 2010;362:494-503.
4. Dixon BS, Beck GJ, Vazquez MA, et al. Effect of dipyridamole
plus aspirin on hemodialysis graft patency. N Engl J Med 2009;
360:2191-201.
5. White JJ, Bander SJ, Schwab SJ, et al. Is percutaneous trans-
luminal angioplasty an effective intervention for arteriovenous
graft stenosis? Semin Dial 2005;18:190-202.
6. Vesely TM, Siegel JB. Use of the peripheral cutting balloon to
treat hemodialysis-related stenoses. J Vasc Interv Radiol 2005;
16:1593-603.
7. Clark TW. Nitinol stents in hemodialysis access. J Vasc Interv
Radiol 2004;15:1037-40.
8. ClinicalTrials.gov. GORE VIABAHN Endoprosthesis Versus
551
 editorials

Percutaneous Transluminal Angioplasty (PTA) to Revise AV Grafts
in Hemodialysis (REVISE) study. (ClinicalTrials.gov number,
NCT00737672.) (Accessed January 21, 2010, at http://clinicaltrials
.gov/ct2/show/NCT00737672.)
9. Shemesh D, Goldin I, Zaghal I, Berlowitz D, Raveh D, Olsha
D. Angioplasty with stent graft versus bare stent for recurrent
cephalic arch stenosis in autogenous arteriovenous access for
hemodialysis: a prospective randomized clinical trial. J Vasc Surg
2008;48:1524-31.
10. Bakken AM, Protack CD, Saad WE, Lee DE, Waldman DL,
Davies MG. Long-term outcomes of primary angioplasty and
primary stenting of central venous stenosis in hemodialysis pa-
tients. J Vasc Surg 2007;45:776-83.
Copyright 2010 Massachusetts Medical Society.

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The New England Journal of Medicine

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Copyright 2010 Massachusetts Medical Society. All rights reserved.