Endovascular Treatment of Peripheral Artery Disease in VA Healthcare System

Endovascular Treatment of Peripheral Artery Disease in

VA Healthcare System

Subhash Banerjee, MD, FACC, FSCAIChief, Division of Cardiology

VA North Texas Health Care SystemDallas, 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

PAD: Endovascular Intervention, Surgery & Amputation Trends: 1996-2006

100

200

300

400

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Num

ber o

f pro

cedu

res /

100,

000

Med

icar

e be

nefic

iarie

s

YearsJ Vascular Surgery 2009; 50:54-60

Total endovascular interventionsRR=3.3; 95% CI 2.9-3.8

Major LE amputationRR=0.71; 95% CI 0.7-0.8

LE bypass surgeryRR=0.58; 95% CI 0.5-0.7

3x growth in endovascular interventions

PAD Endovascular Intervention Trends: 1996-2006

100

200

300

400

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Num

ber o

f pro

cedu

res /

100,

000

Med

icar

e be

nefic

iarie

s

Years

Total endovascular interventionsRR=3.3; 95% CI 2.9-3.8

AngioplastyRR=2.5; 95% CI 2.2-2.8

AtherectomyRR=43.1; 95% CI 34.8-52.0

J Vascular Surgery 2009; 50:54-60PAD: peripheral artery disease

PAD Operator Trends: 1996-2006

100

200

300

400

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Num

ber o

f pro

cedu

res /

100,

000

Med

icar

e be

nefic

iarie

s


CardiologistRR=2.5; 95% CI 2.2-2.8

Vascular surgeonRR=2.5; 95% CI 2.2-2.8

Interventional radiologistRR=2.5; 95% CI 2.2-2.8

Proportion of PAD Endovascular Intervention: 1996-2006


20

40

60

80

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

Prop

ortio

n of

all

endo

vasc

ular

pro

cedu

res

100

Radiologists

Cardiologists

Vascular surgeons10%

40%23%

41%67%

19%

U.S. Market Report. Lifesciences Intelligence Inc. May 2014

U.S. PAD Trends: 2004-2013

2004 2008 20130

1

2

3

4

5

PVI (

mill

ion)

2004 2008 20130

0.5

1

1.5

2

2.5

USD

(bill

ion)

Number of Annual Procedures Estimated Annual Cost

3.23.6

4.3

0.91.3

2.0

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 interventionsCTO: chronic total occlusionDCS & DES (drug-eluting stent) interchangeable

Complication Rates for Endovascular vs. Open Revascularization: 1998 vs. 2007

Egorova et al. J Vasc Surg. 2010

New York State inpatient and outpatient database1998 2007 pEndovascular revascularizationOperative 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 revascularizationOperative 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

New York State inpatient and outpatient database

Diabetes Care 34:1157–1163, 2011

PAD Trends in Veterans: 2000-2004

VA inpatient and outpatient database82% increase in patients with established PAD diagnosis

Patie

nts

405,580

2000 20040

200000

400000

600000

800000 739,377

82% increase

Predictive Value of ABI in Patients with Established CAD (XLPAD® Registry)

Banerjee et al. Am J Cardiol. 2014 Apr 15;113(8):1280-4

ABI<0.9(58.4%)

ABI=0.9-1.4(38.7%)

ABI>1.4(2.9%)

Prevalence of Abnormal ABI in Patients with Stable CAD

ABI: ankle-brachial index, CAD: coronary artery disease, Normal ABI (>0.9 and <1.4), Abnormal ABI (<0.9 and >1.4)

n=679

www.xlpad.org

Predictive Value of ABI in Patients with Established CAD (XLPAD® Registry)

Banerjee et al. Am J Cardiol. 2014 Apr 15;113(8):1280-4


Freedom form Major Adverse Cardiovascular Events (MACE)

No DM, Normal ABIDM, Normal ABINo DM, Abnormal ABIDM, Abnormal ABI

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)

0.0

0.2

0.4

0.6

0.8

1.0

500 1000 1500 2000 2500 3000

Follow-up (days)

Surv

ival

pro

babi

lity

DiabeticsNon-diabeticsLog-rank, p-value <0.001

Kamlesh at al. Clin. Cardiol. 32, 8, 442–446 (2009)

Annual Mortality of Veterans with PAD:DM vs. Non-DM

VA inpatient and outpatient database-199833,629 patients with PAD; 9,474 (29%) with DM*

60-day mortality no different, Mortality significantly increased at 6m for DM

subjects (9.8% vs 8.4%, p<0.001) & continued to 8y

*VA Austin database

Statin Therapy & Limb Outcomes in Patients with PAD: (REACH Registry)

Series10

10

20

30

2221.1

14.7

18.2

3.8

26.225.1

18.2

21.7

5.6

On statin Not on statin

Worsening PAD

New amputationNew limb revascularization

Worsening claudication/ new CLI

Worsening PAD(competing risks)

%

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

n=5,8614-year follow-up

Endovascular Revascularization & Supervised Exercise For Claudication (ERASE Trial)

Fakhry et al. AHA 2013 Late-breaking trial

1 month 6 month 12 month0

400

800

1200

1600

SETEVR+SET

Max

imum

wal

king

dist

ance

(m)

(n=106)

(n=106)

Endovascular revascularization plus supervised exercise therapy is associated with greater improvement in functional performance in patients with PAD

Multicenter Randomized Clinical Trial

0

25%

50%

75%

100%

50 100 150 200 250 300 350 400 450 500 550

ASA+Clopidogrel (n=426)

ASA+Placebo (n=425)

Overall: HR=0.98; 95% CI: 0.78-1.23)

Primary endpoint was significantly reduced by clopidogrel in prosthetic graft patients (HR=0.65; 95% CI: 0.45-0.95; p=0.025)

No significant difference in severe bleeding: clopidogrel+ASA=2.1% vs. ASA+placebo=1.2%

Prop

ortio

n ev

ent-f

ree

(%)

Belch et al. J Vasc. Surg. October 2010

CASPER Trial: DAPT After Peripheral Arterial Bypass Surgery

DAPT: Dual anti-platelet therapy

Major Adverse Event (MAE)-Free Survival with ≤3m or >3m of DAPT

p=0.0024

≤ 3 months DAPT (n=203)

> 3 months DAPT (n=131)

MAE

-free

Sur

viva

l

Months

≤3 months DAPT>3 months DAPT

0.55

0.68

Das S et al. SCAI Annual Mtng. 2014

Diabetes Care 34:1157–1163, 2011

Lower Extremity Amputation Trends Veterans with PAD: 2000-2004

VA inpatient and outpatient database82% increase in patients with established PAD diagnosis

2000 20040

2

4

6

8

Ampu

tatio

ns/1

000

patie

nts

7.08

4.65

34% decline

Crossing Peripheral CTO (XLPAD® Registry)


Proximal cap

Distal capDistal target

vessel

CTO body

Side branch

a b c

Figure: (a) Parts of a typical SFA CTO (b) Inability to direct the wire in a SFA CTO (c) Formation of a wire loop and passage advanced through the sub-intimal space. Arrow head indicates the width of the wire loop and the size of the potential sub-intimal space created

40-50% patients with

symptomatic PAD have a

peripheral artery CTO1

1Norgen et al. J Vasc Surg 2007; 45: S5-67

Peripheral Artery CTO: Surgery vs. PVI

Authors n Lesions Primary endpoint

PVI vs. Surgery Comments

Adam et al.1 452 Infrainguinal Amputation-free survival

71.0% vs. 68.0% (12m); p=ns

5y-multicenter randomized, CLI; no difference at 5y

Wolf et al.2

(VA CSP 199)263 Iliac &

infrainguinalClinicalpatency

64.1% vs. 68.1% (4y); p=ns

4y-multicenter randomized, claudication & CLI; no difference at 6y

McQuade et al.3 100 SFA CTO Clinical patency

72.0% vs. 66.0% (320d); p=ns

2y-single center, prospective, randomized; PTFE stent vs. PTFE bypass graft; no difference at 2y

1. Adam et al. Lancet 2005;366:1925–19342. Wolf et al. JVIR 1993;4:639-6483. McQuade et al. J Vasc Surg 2010;52:584-91

PVI: peripheral vascular intervention

Peripheral Artery CTO: Crossing StudiesFemoropopliteal 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, prospective1. 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 type12m

Primary patency

Mean lesion length Comments

‘Nitinol Self-expanding StentsHong 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 StentsLepantalo et al.6 23 ThrupassTM 48% 160mm Multicenter randomized (terminated)

Farraj et al.6 32 ViabahnTM 86% 154mm Single arm, prospective

Drug-coated stentsBosiers 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 self-expanding 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

1 2 3 40

10

20

30

40

50

60

70

FAST1 Schilinger Angio2 Schilinger DUS2 RESILIENT3

31.7 38.6

p=0.38

24.0 43.0

p=0.05

25.0 45.0

p=0.06

18.7 63.3

p<0.001

Rest

enos

is (%

)

Stent PTA

n=123 n=121 n=51 n=53 n=51 n=53 n=134 n=72

12m 6m 6m 12m

Low –Intermediate complexity patients (~30% DM) & lesions (Mean=69.6 mm)

1. Circulation. 2007 Jul 17;116(3):285-92 2. N Engl J Med 2006; 354:1879-1888 3. Circulation: CV Interventions.2010; 3: 267-276

*Compared to reference group

Cumulative Hazard of Restenosis (CTO vs. Non-CTO SFA Lesions)With Bare-Metal Stent Post-dilation Strategies

Cum

ulat

ive

haza

rd o

f re

sten

osis

Time (in days)

Conventional CTOConventional non-CTOCryoplasty CTOCryoplasty non-CTO

Reference Group

HR=2.65, 95% CI 0.72 – 9.80; p=0.15*

HR=2.69, 95% CI 0.74 – 9.85; p=0.13*

HR=3.61, 95% CI 0.99 –13.18; p=0.05*

Peripheral Artery CTO: Treatment Strategy

Banerjee et al. J Am Coll Cardio 2012; 60(15): 1352-1359

Peripheral Drug Coated StentZilver PTX (Paclitaxel) Trial: Design

Femoro-popliteal lesions (n=508)

PTAn=251

DESn=247

Optimal PTA Failed PTAn=126

DESn=68

BMSn=68

479 patients with Rutherford category ≥ 2 PAD symptomsUp to 2 lesions per SFA

Primary effectiveness end point:primary patency at 12 months. defined by DUS or angio

“As prespecified, acute PTA failure was counted as a loss of patency for the primary effectiveness end point.”

Dake et al. Circ. Interv. Oct. 2011

Lesion length = 64.8 mmCTO = 27.2%

89.9%* 73.0%

32.8% 83.1%*

PTA: balloon angioplasty; DES: drug-eluting stent; BMS: bare metal stent; *p≤0.01

Peripheral Drug Coated Stents

Trial Control Inclusion Criteria

Drug/ Dose (µg/mm2)

Follow-Up (months)

Restenosis* vs. Control

Zilver PTXN=479 PTA & BMS Femoropopliteal

stenosis Paclitaxel/3.0 24 19% vs. 37%

SIROCCOn=93 BMS Femoropopliteal

stenosis Sirolimus/0.9 24 23% vs. 21%

PARADISEn=106 N/A BTK stenosis Paclitaxel/1.4 27 12%

Yukon-BTKn=161 BMS BTK stenosis Sirolimus 24 19% vs. 44%

STRIDESn=104 N/A Femoropopliteal

stenosisEverolimus/

2.25 12 32%

DESTINYn=140 BMS BTK stenosis Everolimus/

2.25 12 21% vs. 47%

Karan Sarode, David Spelber et al. JACCI 2014 (accepted manuscript)

Peripheral Drug Coated Balloons

Trial Study Inclusion Criteria

Balloon/Dose(µg/mm2)

Follow-Up

(months)

Restenosis* vs. Control

THUNDERn=154

DCB vs. PTA vs. PTA + Paclitaxel

in contrast

Femoropopliteal stenosis

Paclitaxel-iopromide/3.0 48 17% vs. 44% vs.

54%

FemPacn=87 DCB vs. PTA Femoropopliteal

stenosisPaclitaxel-

iopromide/3.018 7% vs. 17%

LEVANT In=101 DCB vs. PTA Femoropopliteal

stenosis

Paclitaxel-polysorbate/sorbitol/2.0

6 28% vs. 51%

PACIFIERn=91 DCB vs. PTA Femoropopliteal

stenosis Paclitaxel-urea/3.0 12 7% vs. 35%

LEVANT 2n = 476 DCB vs. PTA Femoropopliteal

stenosis

Paclitaxel-polysorbate/sorbitol/2.0

6

7.7% vs. 17.3%

DEBATE-BTKn=132 DCB vs. PTA Diabetes, BTK

stenosis Paclitaxel-urea/3.0 12 27% vs. 74%

DEBATE SFAn = 110

DCB + BNS vs. PTA + BNS

Femoropopliteal stenosis Paclitaxel-urea/3.0 12 17.0% vs. 47.3%

Karan Sarode, David Spelber et al. JACCI 2014 (accepted manuscript)

VA Peripheral Artery Disease Research: 191 studies 2001-2014

VA Trials 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

www.clinicaltrials.gov

Veteran Affairs Research Programs

VA Research and Quality Improvement ProgramsVA Cooperative Studies Program (CSP): planning and conduct of large multicenter clinical trials and epidemiological studiesResearch 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 qualityMillion Veteran Program (MVP): Data collected from MVP will be stored anonymously for research on diseases like diabetes and cancer, and military-related illnessesResearch Equipment Quick Use Initiative Program (REQUIP): REQUIP is responsible for redistribution of quality, excess, nonexpendable research equipmentVA 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 practiceVA 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


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 Clark Gregg, MD John Rumsfeld, MD Joseph Hill, MD, PhD Anand Prasad, MD Nicolas Shammas, MD Osvaldo S. Gigliotti, MD Mazen Abu Fadel, MD Tayo Addo, MD Mirza Shadman Baig, MD Michael Luna, MD Dharam Kumbhani, MD Andrew Klein, MD Jeffry Hastings, MD Gerold Grodin, MD

Bernadette Speiser, RN Shuaib Abdullah, MD Joseph Garcia, MD Knyugen Kytai, PhD Xu Hao, PhD Atif Mohammad MD Preeti Kamath, BDS Michele Lytal, RN Evaster Bennett, LVN Puja Garg, PhD Swagata Das, MBBS Karan Sarode, BS Gene Pershwitz, MD David Spelber, MD Salil Sethi, MD

Pooja Banerjee, MD Bertis Little, PhD Rick Weideman, PharmD Kevin Kelly, PharmD Cheryl Webb-Singh Donald Haagan, RVT Teresa Jeong, RN Susan Droughty, RN Lauren Makke, RVT Dwaine William Omar Hadidi, MD Rahul Thomas, MD OUR PATIENTS

Endovascular Treatment of Peripheral Artery Disease in VA Healthcare System

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