Endovascular Treatment of PAD at the Veteran Affairs

Report
Endovascular Treatment of
Peripheral Artery Disease in
VA Healthcare System
Subhash Banerjee, MD, FACC, FSCAI
Chief, Division of Cardiology
VA North Texas Health Care System
Dallas, TX
SCAI 2014, Las Vegas, AZ
Endovascular Interventions in
Veterans Affairs Health Care System
 Evolving trends in endovascular interventions:
 National trends
 VA trends
 Patient outcomes:
 Medical therapy
 Detection of PAD in Veteran population
 Dual anti-platelet therapy (DAPT)
 Interventional therapies:
 Chronic total occlusions (CTO)
 Drug-coated balloons (DCB) & drug-coated stents (DCS)
 VA training programs
 PAD research in the VA
Endovascular Interventions in
Veterans Affairs Health Care System
 Evolving trends in endovascular interventions:
 National trends
 VA trends
 Patient outcomes:
 Medical therapy
 Detection of PAD in Veteran population
 Dual anti-platelet therapy (DAPT)
 Interventional therapies:
 Chronic total occlusions (CTO)
 Drug-coated balloons (DCB) & drug-coated stents (DCS)
 VA training programs
 PAD research in the VA
PAD: Endovascular Intervention, Surgery &
Amputation Trends: 1996-2006
Number of procedures /100,000 Medicare beneficiaries
3x growth in endovascular interventions
Total endovascular interventions
RR=3.3; 95% CI 2.9-3.8
400
300
Major LE amputation
RR=0.71; 95% CI 0.7-0.8
200
LE bypass surgery
RR=0.58; 95% CI 0.5-0.7
100
1996
2006
1997
1998
1999
2000
2001
2002
2003
2004
2005
Years
J Vascular Surgery 2009; 50:54-60
Number of procedures /100,000 Medicare beneficiaries
PAD Endovascular Intervention Trends: 1996-2006
Total endovascular interventions
RR=3.3; 95% CI 2.9-3.8
400
300
Angioplasty
RR=2.5; 95% CI 2.2-2.8
200
Atherectomy
RR=43.1; 95% CI 34.8-52.0
100
1996
2006
1997
PAD: peripheral artery disease
1998
1999
2000
2001
2002
2003
2004
2005
Years
J Vascular Surgery 2009; 50:54-60
Number of procedures /100,000 Medicare beneficiaries
PAD Operator Trends: 1996-2006
Cardiologist
RR=2.5; 95% CI 2.2-2.8
400
Vascular surgeon
RR=2.5; 95% CI 2.2-2.8
300
Interventional radiologist
RR=2.5; 95% CI 2.2-2.8
200
100
1996
2006
1997
1998
1999
2000
2001
2002
2003
2004
2005
Years
J Vascular Surgery 2009; 50:54-60
Proportion of PAD Endovascular Intervention: 19962006
100
10%
Vascular surgeons
Proportion of all endovascular procedures
80
40%
23%
60
Cardiologists
40
41%
67%
Radiologists
20
19%
1996
2006
1997
1998
1999
2000
2001
2002
2003
2004
2005
Years
J Vascular Surgery 2009; 50:54-60
U.S. PAD Trends: 2004-2013
Number of Annual Procedures
5
3.2
2.0
3.6
2
3
2
1
0.5
0
0
2008
2013
1.3
1.5
1
2004




2.5
4.3
USD (billion)
PVI (million)
4
Estimated Annual Cost
0.9
2004
2008
2013
Endovascular interventions ~1.5x coronary interventional volume
Endovascular interventional market annual growth rate >8%
Peripheral artery drug-coated stents (DCS): fastest growing sector
CTO crossing device: third highest growth after DES and drug-coated balloons
PVI: peripheral vascular interventions
CTO: chronic total occlusion
DCS & DES (drug-eluting stent) interchangeable
U.S. Market Report. Lifesciences Intelligence Inc. May 2014
Complication Rates for Endovascular vs. Open
Revascularization: 1998 vs. 2007
New York State inpatient and outpatient database
New York State
inpatient and outpatient
1998
2007 database
p
Endovascular revascularization
Operative mortality
2.4%
1.1%
<0.05
Cardiac
1.6%
0.8%
<0.0001
Stroke
0.2%
0.1%
0.04
Bleeding
9.9%
6.7%
<0.0001
Infection
1.7%
1.3%
0.02
Open surgical revascularization
Operative mortality
3.9%
2.7%
<0.05
Cardiac
3.0%
2.2%
0.0006
Stroke
0.4%
0.3%
0.03
Bleeding
14.3%
10.8%
<0.0001
Infection
3.4%
3.8%
0.10
Egorova et al. J Vasc Surg. 2010
PAD Trends in Veterans: 2000-2004
VA inpatient and outpatient database
82% increase in patients with established PAD diagnosis
800000
739,377
82% increase
Patients
600000
405,580
400000
200000
0
2000
2004
Diabetes Care 34:1157–1163, 2011
Endovascular Interventions in
Veterans Affairs Health Care System
 Evolving trends in endovascular interventions:
 National trends
 VA trends
 Patient outcomes:
 Medical therapy
 Detection of PAD in Veteran population
 Dual anti-platelet therapy (DAPT)
 Interventional therapies:
 Chronic total occlusions (CTO)
 Drug-coated balloons (DCB) & drug-coated stents (DCS)
 VA training programs
 PAD research in the VA
Predictive Value of ABI in Patients with
Established CAD (XLPAD® Registry)
Prevalence of Abnormal ABI in Patients with Stable CAD
n=679
ABI=0.9-1.4
(38.7%)
ABI<0.9
(58.4%)
ABI>1.4
(2.9%)
ABI: ankle-brachial index, CAD: coronary artery disease, Normal
ABI (>0.9 and <1.4), Abnormal ABI (<0.9 and >1.4)
www.xlpad.org
Banerjee et al. Am J Cardiol. 2014 Apr 15;113(8):1280-4
Predictive Value of ABI in Patients with
Established CAD (XLPAD® Registry)
Freedom form Major Adverse Cardiovascular Events (MACE)
No DM, Normal ABI
(Reference group)
DM, Normal ABI
(HR=1.7, 95% CI: 0.71-4.06, p=0.24)
No DM, Abnormal ABI
(HR=2.03, 95% CI: 0.83-4.98, p=0.12)
DM, Abnormal ABI
(HR4.85, 95% CI: 2.22-10.61, p=0.0001)
No DM, Normal ABI
DM, Normal ABI
No DM, Abnormal ABI
DM, Abnormal ABI
ABI: ankle-brachial index, CAD: coronary artery disease, Normal
ABI (>0.9 and <1.4), Abnormal ABI (<0.9 and >1.4)
Banerjee et al. Am J Cardiol. 2014 Apr 15;113(8):1280-4
Annual Mortality of Veterans with PAD:
DM vs. Non-DM
VA inpatient and outpatient database-1998
33,629 patients with PAD; 9,474 (29%) with DM*
1.0
Diabetics
Non-diabetics
Log-rank, p-value <0.001
Survival probability
0.8
0.6
0.4
0.2
0.0


60-day mortality no different,
Mortality significantly increased at 6m for DM
subjects (9.8% vs 8.4%, p<0.001) & continued to
8y
500
1000
1500
2000
2500
3000
Follow-up (days)
*VA Austin database
Kamlesh at al. Clin. Cardiol. 32, 8, 442–446 (2009)
Statin Therapy & Limb Outcomes in
Patients with PAD: (REACH Registry)
30
26.2
22
On statin
25.1
21.7
21.1
20
18.2
%
18.2
Not on statin
n=5,861
4-year follow-up
14.7
10
5.6
3.8
0
Worsening
PAD
Worsening PAD
(competing risks)
Worsening claudication/
new CLI
New limb
revascularization
New amputation
 Prior studies have documented improvements in walking distance & coronary revascularization
 This is the first study to demonstrate the impact of statins on adverse limb outcomes
Kumbhami et al. EHJ 2014
Endovascular Revascularization & Supervised
Exercise For Claudication (ERASE Trial)
Multicenter Randomized Clinical Trial
Maximum walking distance (m)
1600
1200
SET (n=106)
EVR+SET
(n=106)
800
400
0
1 month
6 month
12 month
Endovascular revascularization plus supervised exercise therapy is associated with
greater improvement in functional performance in patients with PAD
Fakhry et al. AHA 2013 Late-breaking trial
CASPER Trial: DAPT After Peripheral
Arterial Bypass Surgery
Overall: HR=0.98; 95% CI: 0.78-1.23)
100%
Proportion event-free (%)
ASA+Clopidogrel (n=426)
75%
50%
25%
0
Primary endpoint was significantly reduced by
clopidogrel in prosthetic graft patients (HR=0.65;
95% CI: 0.45-0.95; p=0.025)
50
100
150
200
250
300
350
400
ASA+Placebo (n=425)
450
500
550
No significant difference in severe bleeding: clopidogrel+ASA=2.1% vs. ASA+placebo=1.2%
DAPT: Dual anti-platelet therapy
Belch et al. J Vasc. Surg. October 2010
MAE-free Survival
Major Adverse Event (MAE)-Free
Survival with ≤3m or >3m of DAPT
0.68
0.55
p=0.0024
≤3 months DAPT
>3 months DAPT
≤ 3 months DAPT (n=203)
> 3 months DAPT (n=131)
Months
Das S et al. SCAI Annual Mtng. 2014
Lower Extremity Amputation Trends Veterans
with PAD: 2000-2004
VA inpatient and outpatient database
82% increase in patients with established PAD diagnosis
8
Amputations/1000 patients
7.08
34% decline
6
4.65
4
2
0
2000
2004
Diabetes Care 34:1157–1163, 2011
Endovascular Interventions in
Veterans Affairs Health Care System
 Evolving trends in endovascular interventions:
 National trends
 VA trends
 Patient outcomes:
 Medical therapy
 Detection of PAD in Veteran population
 Dual anti-platelet therapy (DAPT)
 Interventional therapies:
 Chronic total occlusions (CTO)
 Drug-coated balloons (DCB) & drug-coated stents (DCS)
 VA training programs
 PAD research in the VA
Crossing Peripheral CTO
(XLPAD® Registry)
a
b
c
 40-50% patients with
symptomatic PAD have a
peripheral artery CTO1
Proximal cap
Side branch
CTO body
Distal cap
Distal target
vessel
Figure: (a) Parts of a typical SFA CTO (b) Inability to direct the wire in a SFA CTO (c) Formation of a wire
andcoronary
passage advanced
through the
sub-intimal space. Arrow head indicates the width of the wire loop
ABI: ankle-brachial index,loop
CAD:
artery disease,
Normal
and theABI
size(<0.9
of theand
potential
ABI (>0.9 and <1.4), Abnormal
>1.4)sub-intimal space created
1Norgen
et al. J Vasc Surg 2007; 45: S5-67
Peripheral Artery CTO: Surgery vs. PVI
Authors
Primary
endpoint
PVI vs.
Surgery
n
Lesions
Adam et al.1
452
Infrainguinal
Amputationfree survival
71.0% vs. 68.0% 5y-multicenter randomized,
(12m); p=ns
CLI; no difference at 5y
Wolf et al.2
(VA CSP 199)
263
Iliac &
infrainguinal
Clinical
patency
64.1% vs. 68.1% 4y-multicenter randomized,
(4y); p=ns
claudication & CLI; no
difference at 6y
McQuade et al.3
100
SFA CTO
Clinical
patency
72.0% vs. 66.0% 2y-single center, prospective,
(320d); p=ns
randomized; PTFE stent vs.
PTFE bypass graft; no
difference at 2y
PVI: peripheral vascular intervention
Comments
1. Adam et al. Lancet 2005;366:1925–1934
2. Wolf et al. JVIR 1993;4:639-648
3. McQuade et al. J Vasc Surg 2010;52:584-91
Peripheral Artery CTO: Crossing Studies
Femoropopliteal Wire-catheter vs. Crossing Device Outcomes
Authors
n
Crossing
strategy
Crossing
success
Major
Complications
Comments
‘Wire catheter’
Van der Heijden et al.1
-
‘Wire catheter’
60%
Not reported
Retrospective
Charalambous et al.4
76
‘Wire catheter’
65.8%
Not reported
Single arm, prospective
Pigott et al.11
88
‘Wire catheter’
4.5%
0%
Multicenter, prospective
Banerjee et al.2
45
‘Wire catheter’
66%
4%
COBRA trial: prospective, rand.
Dedicated CTO device
Banerjee et al.9
13
TruPath™
77%
0%
XLPAD registry
Charalambous et al.4
26
Frontrunner™
88.1%
3.8%
Single arm, prospective
Zeller et al.6
37
Enabler™
86%
3%
Single arm, prospective
Banerjee et al.10
58
VianceTM★
87.9%
1.7%
XLPAD registry
Massop et al.7
16
Frontrunner™
65%
2.3%
Single arm, prospective
Banerjee et al.5
17
CrossBoss™★
100%
0%
Retrospective
Staniloae et al.8
73
Crosser™
87.7%
0%
Single arm, prospective
Galassi et al.3
36
Crosser™
76.7%
0%
Prospective registry
Pigott et al.11
84
WildCat™
89%
4.8%
Multicenter, prospective
1. Van der Heijden FH et al. Br J Surg 1993;80:959-63; 2. Banerjee S. et al. J Am Coll Cardiol 2012; 3. Galassi AR et al. J Invasive Cardiol 2011;23:359–362; 4. Charalambous N et al. Cardiovasc Intervent Radiol
2010;33:25-33; 5. Banerjee S et al. JEVT 2014; 6. Zeller T et al. JEVT 2012; 7. Mossop PJ et al. CCI 2006; 8. Staniloae CS et al. JIC 2011; 9. Banerjee et al. JEVT 2014; 10. Banerjee et al. JIC 2014 (accepted);
11. Pigott et al. J Vasc Surg. 2012. ★CrossBossTM is the same device as VianceTM
Peripheral Artery CTO: Stent Studies
Authors
n
Stent type
12m
Mean lesion
Primary
length
patency
Comments
‘Nitinol Self-expanding Stents
Hong et al.1
150
EverFlexTM
77.0%
226mm
Single arm, retrospective
Lagana et al.2
52
Multiple
76.9%
Not reported
Single arm, retrospective
Lagana et al.3
93
Multiple
69.2%
255mm
Single arm, retrospective
Dosluoglu et al.4
45
SmartTM
69.0%
Not reported
Single arm, retrospective
Banerjee et al.5
45
Multiple
53%
190mm
Multicenter randomized
Covered Stents
Lepantalo et al.6
23
ThrupassTM
48%
160mm
Multicenter randomized (terminated)
Farraj et al.6
32
ViabahnTM
86%
154mm
Single arm, prospective
Drug-coated stents
Bosiers et al.8
135
Zilver PTX
77.6%
226mm
Single arm, prospective
1. Hong et al. JEVT 2013;20:782–791 ; 2. Lagana et al. Radiol Med 2011;116:444–453; 3. Lagana et al. Radiol Med
2008; 113:567-577; 4. Dosluoglu et al. J Vasc Surg 2008;48:1166–1174; 5. Banerjee et al. J Am Coll Cardio 2012;
60(15): 1352-1359; 6. Lepantalo et al. Eur J Vasc Endovasc Surg 2009;37:578–584; 7. Farraj et al. J Invasive Cardiol.
2009 Jun;21(6):278-81; 8. Boisiers et al. J Cardiovas Surg 2013;54(1):115-22
Crossing Peripheral CTO
(VA Cooperative Trial; VA CSP 598)
Flowchart of the proposed study design.
SFA = superficial femoral artery; CTO = chronic total occlusion; IVUS = intravascular ultrasound; BMS= bare metal Nitinol selfexpanding stents; DES= drug-eluting Nitinol self-expanding stents; R = randomization; m = month; FU = follow-up; R1= first
randomization based on either use of wire-catheter or dedicated crossing device; R2= second randomization to either drug-coated or
bare Nitinol self-expanding stents; ABI= ankle-brachial index
Banerjee et al. VA CSP LOI, 2012
Femoropopliteal Stent: Randomized Trials
Low –Intermediate complexity patients (~30% DM) & lesions (Mean=69.6 mm)
70
Stent
PTA
p<0.001
60
Restenosis (%)
50
p=0.38
p=0.05
p=0.06
31.7 38.6
24.0 43.0
25.0 45.0
n=123 n=121
n=51
n=51
40
30
20
18.7 63.3
10
0
1FAST
1
12m
1. Circulation. 2007 Jul 17;116(3):285-92
n=53
Schilinger
Angio2
2
6m
n=53
Schilinger
DUS2
3
6m
2. N Engl J Med 2006; 354:1879-1888
n=134 n=72
3
RESILIENT
4
12m
3. Circulation: CV Interventions.2010; 3: 267-276
Peripheral Artery CTO: Treatment Strategy
Cumulative Hazard of Restenosis (CTO vs. Non-CTO SFA Lesions)
With Bare-Metal Stent Post-dilation Strategies
HR=3.61, 95% CI 0.99 –13.18; p=0.05*
Cumulative hazard of
restenosis
Conventional CTO
Conventional non-CTO
Cryoplasty CTO
Cryoplasty non-CTO
HR=2.69, 95% CI 0.74 – 9.85; p=0.13*
HR=2.65, 95% CI 0.72 – 9.80; p=0.15*
Reference Group
Time (in days)
*Compared Banerjee
to reference
etgroup
al. J Am
Coll Cardio 2012; 60(15): 1352-1359
Peripheral Drug Coated Stent
Zilver PTX (Paclitaxel) Trial: Design
479 patients with Rutherford category ≥ 2
PAD symptoms
Up to 2 lesions per SFA
Femoro-popliteal
lesions (n=508)
83.1%*
32.8%
PTA
n=251
DES
n=247
“As prespecified, acute PTA failure was
counted as a loss of patency for the
primary effectiveness end point.”
Failed PTA
n=126
Optimal PTA
DES
n=68
89.9%*
Primary effectiveness end point:
primary patency at 12 months.
defined by DUS or angio
BMS
n=68
Lesion length = 64.8 mm
CTO = 27.2%
73.0%
PTA: balloon angioplasty; DES: drug-eluting stent; BMS: bare metal stent; *p≤0.01
Dake et al. Circ. Interv. Oct. 2011
Peripheral Drug Coated Stents
Drug/ Dose
(µg/mm2)
Follow-Up
(months)
Restenosis*
vs. Control
Trial
Control
Inclusion
Criteria
Zilver PTX
N=479
PTA & BMS
Femoropopliteal
stenosis
Paclitaxel/3.0
24
19% vs. 37%
SIROCCO
n=93
BMS
Femoropopliteal
stenosis
Sirolimus/0.9
24
23% vs. 21%
PARADISE
n=106
N/A
BTK stenosis
Paclitaxel/1.4
27
12%
Yukon-BTK
n=161
BMS
BTK stenosis
Sirolimus
24
19% vs. 44%
STRIDES
n=104
N/A
Femoropopliteal Everolimus/2.2
stenosis
5
12
32%
DESTINY
n=140
BMS
Everolimus/2.2
5
12
21% vs. 47%
BTK stenosis
Karan Sarode, David Spelber et al. JACCI 2014 (accepted manuscript)
Peripheral Drug Coated Balloons
Balloon/Dose
(µg/mm2)
FollowUp
(months)
Restenosis*
vs. Control
48
17% vs. 44% vs.
54%
Trial
Study
Inclusion
Criteria
THUNDER
n=154
DCB vs. PTA vs.
PTA + Paclitaxel
in contrast
Femoropopliteal
stenosis
Paclitaxeliopromide/3.0
FemPac
n=87
DCB vs. PTA
Femoropopliteal
stenosis
Paclitaxeliopromide/3.0
LEVANT I
n=101
DCB vs. PTA
PaclitaxelFemoropopliteal
polysorbate/sorbito
stenosis
l/2.0
6
28% vs. 51%
PACIFIER
n=91
DCB vs. PTA
Femoropopliteal
stenosis
Paclitaxel-urea/3.0
12
7% vs. 35%
DCB vs. PTA
PaclitaxelFemoropopliteal
polysorbate/sorbito
stenosis
l/2.0
6
7.7% vs. 17.3%
LEVANT 2
n = 476
DEBATE-BTK
n=132
DEBATE SFA
n = 110
DCB vs. PTA
Diabetes, BTK
stenosis
Paclitaxel-urea/3.0
DCB + BNS vs.
PTA + BNS
Femoropopliteal
stenosis
Paclitaxel-urea/3.0
18
12
12
7% vs. 17%
27% vs. 74%
17.0% vs. 47.3%
Karan Sarode, David Spelber et al. JACCI 2014 (accepted manuscript)
Endovascular Interventions in
Veterans Affairs Health Care System
 Evolving trends in endovascular interventions:
 National trends
 VA trends
 Patient outcomes:
 Medical therapy
 Detection of PAD in Veteran population
 Dual anti-platelet therapy (DAPT)
 Interventional therapies:
 Chronic total occlusions (CTO)
 Drug-coated balloons (DCB) & drug-coated stents (DCS)
 VA training programs
 PAD research in the VA
VA Peripheral Artery Disease
Research: 191 studies 2001-2014
ClinicalTrials.gov
Identifier
Year
Center for the Study of Vascular Disease in Hispanic and Native
Americans
NCT00018590
2001
Does the Reduction of Total Body Iron Storage (TBIS) Alter Mortality in
a Population of Patients With Advanced PVD? (FeAST)
NCT00032357
2002
Markers and Mechanisms of Vascular Disease in Type II Diabetes
NCT00256646
2005
Low-Dose Opiate Therapy for Discomfort in Dementia (L-DOT)
NCT00385684
2006
Study Comparing Two Methods of Expanding Stents Placed in Legs of
Diabetics With Peripheral Vascular Disease (COBRA)
NCT00827853
2009
Remote Ischemic Preconditioning Prior to Vascular Surgery (CRIPES)
NCT01558596
2012
Micropuncture vs. Standard Common Femoral Artery Access
NCT02026180
2013
VA Trials
www.clinicaltrials.gov
Veteran Affairs Research Programs
VA Research and Quality Improvement Programs
VA Cooperative Studies Program (CSP): planning and conduct of large multicenter clinical
trials and epidemiological studies
Research on Health Disparities and Minority Health: research addressing the challenges
posed by minority health care needs and the disparities that arise in healthcare delivery,
access, and quality
Million Veteran Program (MVP): Data collected from MVP will be stored anonymously for
research on diseases like diabetes and cancer, and military-related illnesses
Research Equipment Quick Use Initiative Program (REQUIP): REQUIP is responsible for
redistribution of quality, excess, nonexpendable research equipment
VA Technology Transfer Program: The mission of the VA Technology Transfer Program (TTP) is
to serve the American public by translating the results of worthy discoveries made by
employees of VA into practice
VA Specimen Research and Biobanking Program: The VA Specimen Research and Biobanking
Program makes tissue samples available for research on illnesses in Veterans
www.research.va.gov
Endovascular Interventions in Veterans
Affairs Health Care System
 Period of rapid growth in endovascular
interventions:
 Prospective trials to establish the impact of ABI screening in
asymptomatic individuals & in patients with established CAD
 Medical interventions in PAD
 Statin & DAPT interventions
 Endovascular interventions in PAD
 Refinement of CTO treatment
 DCB and DCS trials
 Growing role of VA sponsored clinical trials &
databases
Acknowledgements

Emmanouil S. Brilakis, MD, PhD 
Bernadette Speiser, RN

Pooja Banerjee, MD

Clark Gregg, MD

Shuaib Abdullah, MD

Bertis Little, PhD

John Rumsfeld, MD

Joseph Garcia, MD

Rick Weideman, PharmD

Joseph Hill, MD, PhD

Knyugen Kytai, PhD

Kevin Kelly, PharmD

Anand Prasad, MD

Xu Hao, PhD

Cheryl Webb-Singh

Nicolas Shammas, MD

Atif Mohammad MD

Donald Haagan, RVT

Osvaldo S. Gigliotti, MD

Preeti Kamath, BDS

Teresa Jeong, RN

Mazen Abu Fadel, MD

Michele Lytal, RN

Susan Droughty, RN

Tayo Addo, MD

Evaster Bennett, LVN

Lauren Makke, RVT

Mirza Shadman Baig, MD

Puja Garg, PhD

Dwaine William

Michael Luna, MD

Swagata Das, MBBS

Omar Hadidi, MD

Dharam Kumbhani, MD

Karan Sarode, BS

Rahul Thomas, MD

Andrew Klein, MD

Gene Pershwitz, MD

OUR PATIENTS

Jeffry Hastings, MD

David Spelber, MD

Gerold Grodin, MD

Salil Sethi, MD

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