Peripheral Artery Intervention: insights from the XLPAD registry

Subhash Banerjee, MD; FACCChief, Division of Cardiology, VA North Texas Healthcare System

Prof. of Medicine, UT Southwestern Med. Ctr.

Texas FreshAir 2015 Annual Conference

Topics for Discussion Research question:

Peripheral Artery Disease (PAD)

Research infrastructure & methodology: XLPAD registry Core laboratory

Research findings: Key publications Grants

Updated slide kit, February 2006

3

PAD: A Global Epidemic

The global prevalence of PAD increased by 24% from 2000 to 2010, from 164 million to 202 million

32 million peripheral diagnostic & interventional procedures performed annually in the U.S.

55 million

15 million

10 million

45 million

15 million

15 million

42 million

6 million

Fowkes et al. Lancet 2013, volume 382, issue 9901, pages 1329-1340

Long-Term Survival in Patients With PAD

Criqui MH et al. N Engl J Med. 1992;326:381-386.

Normal subjects

Asymptomatic PAD

Symptomatic PAD

Severe symptomatic PAD

100

75

50

25

0 2 4 6 8 10 12

Su

rviv

al (%

)

Year

624 men and women who were residents of a predominantly white, upper-middle-class community in southern CA

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

Banerjee et al. AJC 2013

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

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

Cardiovascular Events Based on ABI values & Diabetes Mellitus

no DM, normal ABI DM, normal ABI no DM, abnormal ABI DM, abnormal ABI0

5

10

15

20

25

1.16

4.483.91

5.524.65

5.977.03

14.29

2.33 2.24

0

4.223.45

4.23

6.15

13.46

7.95

12.4111.45

20.63

1-Y

ear

Eve

nt

Rat

e (%

)

p=0.006

p=0.40

p=0.29

Death Non-fatal myocardial infarction Stroke Repeat coronary revascularization MACE

(n=88) (n=145) (n=131) (n=315)

n=679

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

Banerjee et al. AJC 2013

Freedom form Major Adverse Cardiovascular Events (MACE)

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

(n=88)n=679

(n=88)(n=145)(n=131)

(n=315)

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)

Peripheral Artery Anatomy SFA: superficial femoral

artery

Longest artery, highly dynamic

Repetitive trauma, & prone to atherosclerosis

In a fibromuscular canal

Lack of compensatory expansion, limited collaterals

Site of most frequent endovascular procedures

PAD: highly prevalent in Veterans

Soor GS et al. Pathology 40(4), pp. 385–391

SFA

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

Years J 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

Ehrin Armstrong, MDMazen Abu-Fadel, MDOsvaldo Gigliotti, MDAnand Prasad, MD

Nicolas Shammas, MDAndrew Klein, MDRobert Dieter, MDM Ishti Ali, MD

Subhash Banerjee, MD (Principal investigator)Tony Das, MDGerardo Rodriguez, MDEdiberto Soto-Cora, MD

Established 2013: Total procedures: 2,500 Total patients: 1,600

The XLPAD website: www.xlpad.org, Clinicaltrials.gov #: NCT01904851

Excellence in Peripheral Artery Disease

http://www.xlpad.org

XLPAD Registry Research infrastructure:

UTSW RedCap (NIH) infrastructure & data servers

Contracts with participating sites through UTSW research office

Data transfer agreements with each site On-site monitoring, audit & data

collection Remote access to EMR & cath lab data

archive through third party vendor Approved by VA & non-VA sites

XLPAD Registry

Scientific value: Multicenter (VA &

non-VA; women, inter-disciplinnary)

>92% data audits Independent, blinded

adjudication of clinical & procedural findings

Publications & presentations

Background data for prospective studies

Participant value: 20 peer-reviewed

publications 2014-15 32 national meeting

presentations Data access to site

investigators & students

Peer-peer education Background data for

grants

LDA analyzer

Source DICOM Files

VA North Texas Cardiovascular Core LaboratoryCoronary and Vascular Quantitative Analyses

PVR

Intervention strategy: SFA CTO

SFA CTO

Crossing

Wire-catheter

Crossing device

Treatment

Balloon Stent

Balloons & stents: bare, non-drug coated or anti-proliferative drug coated

SFA; superficial femoral artery; CTO: Chronic total occlusion

CTO Crossing StrategiesCrossing CTO Lesions

CTO Crossing Device Guidewire and Catheter

CXI

GlideCath

Trailblazer

QuickCros

s

NaviCross

Rubicon

Viance

Frontrunner

Wildcat/Ocelot

Crosser

TruePath

Banerjee et al J Invasive Cardiol 2014 26(8): 363-9

Charalambous et al Cardiovasc Intervent Radiol 2010; 33(1): 25-33Shetty et al J Invasive Cardiol 2013; 25(7):344-7

Banerjee et al J Endovasc Ther 2014; 21(2):281-8Bosiers et al J Endovasc Ther 2014; 21(1):61-70

Joye et al Am J Cardiol 2007; 100(Suppl 1):S24Gandini et al J Endovasc Ther 2009; 16(1):23-7Staniloae et al J Invasive Cardiol 2011; 23(9):359-62

Pigott et al J Vasc Surg 2012; 56(6):1615-21

Selmon et al J Endovasc Ther 2013; 20(6):770-81

0.014’’, 0.018’’, and 0.035’’ guidewires

www.xlpad.org

CTO Crossing: Primary technical success

www.xlpad.org

Procedural Success: Successful revascularization of the CTO with a ≤30% residual diameter stenosisWire-catheter CTO-crossing device

CTO Crossing: Secondary technical success

www.xlpad.org

CTO Crossing: provisional technical success

www.xlpad.org

Results: Technical & Procedural Success

Primary Technical Success (%)

51.9

72.1

Wire-Catheter (n=295)

CTO Device (n=143)

P<0.001

Procedural Success (%)

93.6 90.9

P=0.332

Results: 12-month Adverse Events

Death

Endovascular Revascularization

Surgical Revascularization

Unplanned Amputation

Stent Thrombosis

4.7

19.7

8.8

3.4

4.1

3.5

19.5

2.8

2.1

6.3

%

P=0.343

P=0.560

P=0.025

P=1.000

P=0.626

CTO deviceWire catheter

Results: 12-month Clinical Outcomes

Wire-Catheter CTO Device

Before After

P<0.001

Wire-Catheter CTO Device

P<0.001 P<0.001P<0.001

Ankle-Brachial Index

Rutherford Category

3.31 ± 1.24

2.67 ± 1.51

3.22 ± 1.30

2.46 ± 1.53 0.71

± 0.31

0.81 ± 0.24

0.83 ± 0.26

0.70 ± 0.32

Dual antiplatelet therapy (DAPT) Patient Flow Chart

334 unique patients from XLPAD registry (NCT01904851) followed for up to 12

months after index procedure

27 did not receive DAPT

therapy

176 received DAPT therapy for ≤3 months before

discontinuation OR first occurrence of MAE

131 received DAPT therapy for >3 months before

discontinuation OR first occurrence of MAE

“≤3 months DAPT” (n=203)

“>3 months DAPT” (n=131)

www.xlpad.org

12-m outcome analyses: ‘as treated’ & ‘as treatment prescribed’

Banerjee et al. SCAI 2014

www.xlpad.org

≤3 months DAPT (n=203)

>3 months DAPT (n=131)

Results: Major adverse event (MAE)-free survival with ≤3m & >3m DAPT

Hazard ratio*: 1.60 95% Confidence Interval: 1.08-2.43; p=0.019

10

1.0

0.8

0.6

0.4

0.2

0.0

2 4 6 8 12

Months of follow-up

MA

E F

ree S

urv

ival

*Adjusted for age, diabetes, hypertension, hyperlipidemia, smoking, ankle-brachial index, Rutherford category, prior lower-extremity procedure, and coronary artery disease

59.7%

70.3%

p=0.002

a b c d

Figure 1: Case of definite stent thrombosis

Banerjee et al. Circulation 2015 (in review)

Stent-based femoropopliteal peripheral artery intervention (n=724)

Peripheral artery stent thrombosis(n=29; 4.0%)

No peripheral artery stent thrombosis(n=695; 96.0%)

Definite stent thrombosis

(n=23; 3.2%)

Probable stent thrombosis(n=1; 0.1%)

Possible stent thrombosis(n=5; 0.7%)

Timing of stent thrombosis (days)Median=30; 25%-75% IQR=[7-150]

Very late stent/vessel thrombosis(n=2; 0.3%)

Late stent/vessel thrombosis

(n=12; 1.7%)

Early stent/vessel thrombosis

(n=15; 2.1%)

Acute stent/vessel thrombosis(n=5; 0.7%)

Sub-acute stent/vessel thrombosis

(n=10; 1.4%)

Figure 2: Flowchart describing stent thrombosis

Events

At risk

0

717

19

523

23

410

25

285

29

154

Kap

lan

-Mei

er F

ailu

re (

%)

6.3%

0 2 6 10 12Months

4 8

20

40

0

Figure 3: 12-month stent thrombosis rate

Banerjee et al. Circulation 2015 (in review)

BMS (n=541) DCS (n=74) Supera™ (n=57) Viabahn™ (n=52)0

2

4

6

8

10

12

14

3.1

4.1

5.3

11.5

Sten

t Thr

ombo

sis

(%)

Figure 4a: Rate of stent thrombosis by stent type

p=0.011

p=0.72

p=0.43

Figure 5a: 12-month MALE for patients with and without stent thrombosis

Non-stent thrombosis

Stent thrombosis

aAdjusted for age, ABI, diabetes mellitus, CAD, CLI, smoking

aHR=3.04, 95% CI=[1.62-5.25], p=0.001

Kap

lan

-Mei

er F

ailu

re (

%)

Months

27.2%

58.0%

P<0.0001

0 2 4 6 8 10 12

20

40

60

80

100

Figure 5b: 12-month MACE for patients with and without stent thrombosis

Non-stent thrombosis

Stent thrombosisaHR=1.10, 95% CI=[0.69-1.64], p=0.675

aAdjusted for age, ABI, diabetes mellitus, CAD, CLI, smoking

Kap

lan

-Mei

er F

ailu

re (

%)

Months

7.8%

7.7%

P=0.781

0 2 4 6 8 10 120

20

40

Banerjee et al. Circulation 2015 (in review)

Endovascular Intervention Procedural Cost Analysis

Heakyung et al. ACC 2016 Submission

1. Comparative Assessment of Guidewire and Microcatheter versus a Crossing Device–Based Strategy to Traverse Infrainguinal Peripheral Artery Chronic Total Occlusions. Banerjee S, Sarode K, Patel A, Mohammad A, Parikh R, Armstrong EJ, Tsai S, Shammas NW, Brilakis ES. J Endovasc Ther 2015

2. Drug Coated Balloon and Stent Therapies for Endovascular Treatment of Atherosclerotic Superficial Femoral Artery Disease. Banerjee S, Sarode K, Mohammad A, Brilakis ES. Curr Cardiol Rep 2015

3. Optimal Dual Antiplatelet Therapy after Infrainguinal Endovascular Endovascular Revascularization. Sarode K, Mohammad A, Das S, Vinas A, Banerjee A, Brilakis ES, Banerjee S. Ann Vasc Surg 2015

4. Recanalization of Popliteal and Infrapopliteal Chronic Total Occlusions using Viance and CrossBoss Crossing Catheters: a Multicenter Experience from the XLPAD Registry. Sethi S, Mohammad A, Ahmed H, Germanwala S, Sarode K, Ortiz-Lopez C, Banerjee S, Prasad A. J Inv Cardiol. 2015

5. Stent and Non-stent Based Outcomes of Infrainguinal Peripheral Artery Interventions From the Multicenter XLPAD Registry. Banerjee S, Pershwitz G, Sarode K, Mohammad A, Abu-Fadel MS, Baig MS, Tsai S, Little BB, Gigliotti OS, Soto-Cora E, Foteh MI, Rodriguez G, Klein A, Addo T, Luna M, Shammas NW, Prasad A, Brilakis E. J Inv Cardiol. 2015

6. Blunt microdissection for endovascular treatment of infra-inguinal peripheral arterial chronic total occlusions: featured case series, outcomes and comparative description of crossing devices. Banerjee S, Hadidi OF, Mohammad A, Alsamarah A, Thomas R, Sarode K, Garg P, Baig MS, Brilakis ES. J Endovasc Ther. 2014

7. Endovascular treatment of infra-inguinal peripheral arterial chronic total occlusions with the TruePath device: featured case series, device features, handling and procedural outcomes. Banerjee S, Sarode K, Das T, Hadidi OF, Thomas R, Vinas A, Garg P, Mohammad A, Baig MS, Shammas N, Brilakis E. J Endovasc Ther. 2014

8. Significance of an abnormal ankle-brachial index in patients with established coronary artery disease with and without associated diabetes mellitus. Banerjee S, Vinas A, Mohammad A, Hadidi OF, Thomas R, Sarode K, Banerjee A, Garg P, Weideman R, Little B, Brilakis ES. Am J Cardiol. 2014

9. Crossing of Infra-inguinal Peripheral Arterial Chronic Total Occlusion with Viance™ Blunt Microdissection Catheter. Banerjee S, Thomas R, Sarode K, Das T, Hadidi OF, Vinas A, Garg P, Mohammad A, Baig MS, Abu-Fadel M, Shammas NW, Prasad A, Brilakis ES. J Invasive Cardiol. 2014

10. Drug Delivering Technologies for Endovascular Management of Infrainguinal Peripheral Artery Disease. Sarode K, Spelber D, Bhatt D, Mohammad A, Prasad A, Brilakis ES, Banerjee S. J Am Coll Cardiol Intv. 2014

11. Protected PTA in the lower limbs: a step forward in preventing distal embolization. Banerjee S, Sarode K, Brilakis ES. J Endovasc Ther. 201312. Commentary: embolic capture angioplasty with the 300-mm long proteus balloon. Banerjee S, Garg P, Brilakis ES. J Endovasc Ther. 201213. Embolic capture angioplasty in peripheral artery interventions. Hadidi OF, Mohammad A, Zankar A, Brilakis ES, Banerjee S. J Endovasc Ther.

2012

XLPAD Key Publicationswww.xlpad.org

VA Cooperative Clinical Trial (VA CCTA0002)

4 centers ($2.0M)

Translational research

3 industry grants for PAD intervention & atherosclerosis imaging

Real-world device use, efficacy & safety

Interaction of device & drug therapies

Participant QOL & health-economic analysis

Grantswww.xlpad.org

PAD is highly prevalent and is associated with worse cardiovascular and limb outcomes

XLPAD registry provides a unique platform to conduct large-scale multicenter outcomes research in patients with PAD

Findings from the XLPAD registry has provided important scientific data & supported successful grant applications

XLPAD registry could potentially serve as a template for building diverse investigational collaborations

Conclusionswww.xlpad.org

Acknowledgements

Emmanouil S. Brilakis, MD, PhD

Clark Gregg, MD

Richard Miller, MD

Joseph Hill, MD, PhD

Scott Grundy, MD

Anand Prasad, MD

Nicolas Shammas, MD

Osvaldo S. Gigliotti, MD

Mazen Abu Fadel, MD

Tayo Addo, MD

Michael Luna, MD

Dharam Kumbhani, MD

Jeffry Hastings, MD

Gerold Grodin, MD

Shuaib Abdullah, MD

Joseph Garcia, MD

Laura Collins, MD

Nicole Minniefield, 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

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

Tina Terry, RN

Smitha Thomas, RN

Diana Lacey, RN

OUR PATIENTS