Covered Stents to Treat Hemodialysis Access Stenosis in Central

2/5/2015
Covered Stents to Treat
Hemodialysis Access
Stenosis in Central Veins
How much does this matter?
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 In the U.S. alone, $2.9 billion, i.e. ~15% of the total cost
of hemodialysis care is spent on managing access
dysfunction
 Much of the longstanding PTA literature, i.e. ‘standard
therapy,’ is built upon retrospective literature– equally
quoted in DOQI
 Shouldn’t it bear more critical review?
 Doesn’t clinical research warrant replicative studies?
Ziv Haskal MD FSIR FACR FCIRSE FAHA
Professor of Radiology / Interventional Radiology
University of Virginia
Editor in Chief, Journal of Vascular and Interventional
Radiology
Ziv J Haskal MD
Places They Go
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Iatrogenesis (cause of most CV stenoses)
 Emergent use: ruptures
 Central vein stenoses and occlusions
Bare venous stents restenose
centrally just like they do in the
periphery
Virtually every device has been shown,
fractured, in a central location
Ziv J Haskal MD
Early Signal
Central Stents are prone to Iatrogenic Events:
SVC Syndrome: handmade PTFE stent
grafts I sewed in1998
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Migration After Unaware Operator Placed TDC Through Stent
recurrent intra-bare stent stenosis
Impra 4 mm PTFE sewn over Wallstents
Ziv J Haskal MD
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Ziv J Haskal MD
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Revision
Functioning arm: Early Signal: 2000
SVC Syndrome Treated with ePTFE Central Vein Stent Grafts
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Had repeated central vein PTA, nitinol stent, intranitinol stent PTA
<2-3 week effect, in final 2 rounds
9 month follow up after 13mm Viabahn in left inominate
On-label ePTFE central
vein stent grafts is a
desirable goal
Would be nice to have
a mission-specific
device, beyond revision
use of existing designs
Viabahn
18 month follow-up
PTFE graft placed after many recurrent,
symptomatic, bare stent stenoses
Ziv J Haskal MD
Peripheral Long lengths reach into ‘central’ roles:
Arm Swelling, AVG
Central Veins Subset: Cephalic Arch Stenoses
(renal transplant)
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~17+cm
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Cephalic arch stenosis in 26/177 (15%)
•
2/116 Radiocephalic (2%)
•
24/61 Brachiocephalic (39%)
•
Cephalic arch PTA 50 cases
May
2010
•
•
Jan
2011
Rajan DK, et al. JVIR 2003; 14:567–573
29/50 (58%) required “Ultra-high pressure” (>27 ATM)
Higher rupture risk, high restenosis
Kian K, Asif A. Sem Dialy. 2008;12 :78-82
Ziv J Haskal MD
Edge stenoses: Current
designs are not site-specific
Small Comfort in that biological response is similar
in other veins:
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Hepatic Vein Outflow Block and Budd-Chiari
Syndrome
 Unique forces at these sites
 Some stent designs may prove better: match adjacent vessel elastic modulus, stress
sensitive
 42 yo man with
recurrent chronic BCS
10/14 Returns with restenosis after 2 prior PTA
From: Brent et al jvir 2010
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Ziv J Haskal MD
2/3/15 Returns with ‘edge’ stenosis and
recurrent ascites and renal insufficiency
PTA. Time for a new plan
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Venous Stent Grafts: What
Evidence Do We Have?
Cephalic Arch Stent use: Dukkipati et al
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45 cephalic arch stent patients, retrospective. Time to repeat PTA after prior
PTA in TPA only vs ‘Stent’ patients
median PTA patency was 91.5 days with suggested improved bare metal
stent patency with a median patency of 152 days.
 May benefit from different elastic modulus,
 Different flexibilities to reduce torque, shear
stress, edge effects
 Heparin coating might be important
Although patency appeared improved with bare metal stents for CAS in this
study, there is no description of intervention, follow-up methodology, points of
censure or definitions and estimation of patency were provided
We do not know which stent(s) were placed– do not even know if they were
covered or not….
Is this not a failure of the review process?
Even the table lists “PTCA”, which is: Percutaneous transluminal coronary
angioplasty
Ziv J Haskal MD
Dukkipati R, et al Outcomes of Cephalic Arch Stenosis With and Without Stent Placement after Percutaneous Balloon Angioplasty in Hemodialysis Patients.
Semin Dial. 2014 Oct 9. epub.
Ziv J Haskal MD
Cephalic arch stenosis in autogenous
haemodialysis fistulas: treatment with the
Viabahn stent-graft
Viabahn ePTFE stent grafts
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 11 consecutive AVF patients (2005-11), retrospective
 10 access patency: 82 % at 6 mos; 73 % at 12 mos
 20 access patency rates: 91% at 6 mos
• Retrospective; n=25
• 11 x 5 Viabahn or 13mm Fluency
• 8% thormbosis (n=2) at 30, 90d
• 12% edge PTA req’d
• 10 Stent patency: 56% 12 mos
Anaya-Ayala et al. J Vasc Surgery 2011
Ziv J Haskal MD
Long-term results of stent-graft placement to treat central
venous stenosis and occlusion in hemodialysis patients with
arteriovenous fistulas.
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42 Viabahn stent grafts in 30 patients
Prior PTA and/or bare stents in 77%
16 stenoses, 12 occlusions
Mean 705d follow up: Fistulography
10 patency 6 mos: 81%; 100% asst’d
10 patency 12 mos: 67%; 80% asst’d
10 patency 24 mos: 45%; 75% asst’d
Jones et al. JVIR 2011; 22: 1240-5
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Ziv J Haskal MD
Shawter et al. CVIR 2013; 36:133-9
Early randomized data (2008) and signal
Cephalic Arch Bare Stent V. PTFE
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 Luminex vs. Fluency
 25 consecutive patients, >50% stenosis
 Endpoint: >50% stenosis at 3 mos (1 0 p)
Limitations:
 Study had no sample size calculation
 Many devices were extended into subclavian
vein (excluding the axillary vein)
Ziv J Haskal MD
Shemesh et al. J Vasc Surg 2008; 48:1524-31
Ziv J Haskal MD
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Covered Stents to Treat Hemodialysis Access Stenoses in the
Cephalic Arch and Central Veins (U.Toronto), NCT01200914
(n~140): Hep Bonded Viabahn
RESCUE Study
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Prospective, Multi-Center RCT, Concurrently-Controlled Study of Fluency®
Plus for In-stent Restenosis in the AV Access Venous Outflow Circuit
 Prospective 1:1 RCT of PTA vs Viabahn at 3,6,12 mos.
Investigator sponsored study
 After several years, study closed after failing to enroll more than
14 AVF patients across 3 centers (5 randomized to PTA, 9 to SG)
 PTA mean patency 100d
 SG mean patency 300d

Lessons?



23 U.S. investigational sites
Randomization PTA vs. PTA & Fluency® Stent Graft
265 patients randomized / treated
 220 patients included in 6 month effectiveness
analysis

Follow Up at 1, 3, 6, 12, 18 and 24 months
Mandatory angiogram at 90 Days to evaluate binary
restenosis (core lab)
Rajan et al.
Ziv J Haskal MD
Core Lab Analysis
Ziv J Haskal MD
RESCUE Study
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Baseline Data
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Access Circuit Characteristics (n=265)
Stenosis prior Treatment
Right after Fluency® Plus Device
90 Day Follow Up
Source: RESCUE Clinical Study Angiographic Core Lab
RESCUE at 6 months: Access Types and Lesion
Locations– Post-Intervention Lesion Patency (PLP)
RESCUE
Results: Percentage of Access Circuit Primary
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Patency at 6 Months (95% CI)
No significant difference between AV Graft
and Fistula Outcome (p=0.151): Access
Type Did Not Matter
Central Lesions Greater Benefit: Yes,
statistical significance between central vs.
peripheral veins (p= 0.023)
p<0.001
n=109
n=111
Statistically powered to test superiority
Ziv J Haskal MD
ASDIN 2015
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2/5/2015
…Drug Eluting Balloons?
Questions For AV Access?
• Any results so far?
• Control of Dosing and
amounts?
• Control of release kinetics of
drug into a vein wall (is not an
atherosclerotic artery), etc
Perrcutaneous Angioplasty Using a Paclitaxel-Coated Balloon
Improves Target Lesion Restenosis on Inflow Lesions
of
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Autogenous Radiocephalic Fistulas: Pilot Study
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Immunofluorescence micrographs after staining with a monoclonal antitubulin abx
 Random assignment of 20 lesions in 10 patients
Lai et al. JVIR 2013
Control animal 7 days after PTA:
heterogeneous staining within
the neointima.
Rx animal 7d after local paclitaxel
delivery: intensely stained
“fluorescence band” at luminal cell
lining
small sample; single site; some differences in lesions; smaller
coronary PCBs
dysfunction-driven re-referral (rather than scheduled follow up)
may create differences in small group (reporting bias)
Gray W , Granada J F Circulation. 2010;121:2672-2680
Ziv J Haskal MD
Paclitaxel-Coated versus Plain Balloon Angioplasty for
Dysfunctional Arteriovenous Fistulae: One-YearASDIN
Results
of a
2015
Prospective Randomized Controlled Trial
But… Did it provide some Signal?
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DEB
POBA
P= 0.03
DEB
 All pts completed 1 yr f/up
 Superior 1 yr patency for DEB
(paclitaxel) in AVF pts
 SIR Reporting Standards
endpoints (<30% resid stenosis,
ITT, clinical success, etc)
P= 0.04
Final
Ziv J Haskal MD
Conclusions
Ziv Jin
Haskal
MD
Panagiotis M. et al. JVIR
press
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 Hemodialysis access life extension is
dramatically potentiated by the use of
ePTFE stent grafts– for revision, repair,
conversion, etc.
 In-stent restenosis is a current and
reasonable approach for central lesions
 Purpose-designed devices would expand
treatment of central vein stenoses– and
may markedly affect results. This may
not happen
 Initial Rounds will be market driven
expansion of existing products, despite
limitations (proof of P)
Ziv J Haskal MD
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