Michael K. W. Lichtenberg, FESC

REKANALISATION CHRONISCH VENÖSER VERSCHLÜSSE

Conflict of Interest - Disclosure

Within the past 12 months, I or my spouse/partner have had a financial

interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

1. Honoraria for lectures: CR Bard, Veniti, AB Medica, Volcano, Optimed

GmbH, Straub Medical, Terumo, Biotronik, Veryan

2. Honoraria for advisory board activities: Veniti, Optimed GmbH, Straub

Medical, Biotronik, Veryan, Boston Scientific

3. Participation in clinical trials: Biotronik, CR Bard, Veryan, Straub Medical,

Veniti, TVA Medical, Boston Scientific, LimFlow

4. Research funding: Biotronik, Boston Scientific, Veryan, Veniti, AB Medica

C6, 58 year female, postthrombotic syndrome

Sinus XL Stent (22 x 80 mm) 4 x Veniti Stent (16 x 120 mm + 14 x 60 mm)

Significant body of clinical work • Existing stents…Wallstent

• Good success treating obstructive component of many venous disorders

Current generation of stents being studied • VIVO Trial – Zilver Vena (Cook Medical)

• VIRTUS Trial – VICI VENOUS STENT (VENITI, Inc.)

Venous Stenting is Not New

Autor Jahr Stent N = Patienten

Primäre Patency Sekundäre Patency

Lichtenberg (1)

2016 Zilver Vena 35 87.9 % 12 Monate

Ye (2) 2012 Wallstent 205 98.0 % 48 Monate

100 % 48 Monate

Hartung (3) 2009 Wallstent 89 83.0 % 120 Monate

93 % 120 Monate

Neglen (4) 2008 Wallstent 177 86.0 % 72 Monate

93 % 72 Monate

Knipp (5) 2007 Wallstent 54 38.0 % 60 Monate

73 % 60 Monate

Nazarin (6) 1996 Wallstent, Palmaz

55 59-72 % 48 Monate

75 % 48 Monate

Ye K et al. J Vasc Interv Radiol 2012;23: 497-502

Hartung O et al. J Vasc Endovasc Surg 2009;38: 118-24

Nazarin et al. Cardiovasc Intervent Radiol 1996 Jul-Aug;19(4):227-33

Neglen et al. Journal of Vascular Surgery, Volume 48, Pages 1255–1261, 2008

Knipp et al. Journal of Vascular Surgey, Volume 46, Issue 4, Pages 743–749.e1, October 2007

Lichtenberg et al. Oral presentation during DGA annual congress 2016

Venous obstruction • Very different than arterial obstruction, and venous stents

need to do a different job

• Involves high compressive forces from external pressure and/or fibrosis

Why not arterial stents?

• Self-expandable

• Crush resistant across length of stent

• Sufficient chronic outward force

• Sufficient wall coverage

• Flexibility sufficient to resist kink at physiological angles

• Durability allowing repeated shortening, twisting, and bending at the groin

• Minimal foreshortening on deployment and balloon dilation

• Predictable, consistent deployment

Desired Venous Stent Attributes

Goal… Ideal BALANCE strength, flexibility, and lumen quality.

Closed Cell Open Cell

Design Attributes • All struts interconnected • Not all struts interconnected

Performance

Crush Resistance ++ + Flexibility + ++ Coverage ++ +

Performance Characteristics

Radial Force and Crush Resistance

0,146

0,049

0,030

BARD VENOVO 14X160 N=20

OPTIMED SINUS VENOUS 14X80

N=3

COOK ZILVER VENA 14X100

N=2

Rad

ial R

esis

tive

Fo

rce

at

1m

m o

vers

ize

(N

/mm

)

Radial Resistive Force

2,65

1,94

1,18

BARD VENOVO 14X160 N=20

OPTIMED SINUS VENOUS 14X80

N=3

COOK ZILVER VENA 14X100

N=3

Loca

l Co

mp

ress

ion

Fo

rce

(N

)

Crush Resistance

Bench testing may not be indicative of clinical performance. Different test

methods may yield different results. Competitive testing samples represent

commercially available venous stents with CE mark as of June 2014.

This product is not available for sale in the US

Stent Flexibility

1,29

0,62

0,43

BARD VENOVO 14X160 OPTIMED SINUS VENOUS 14X80

COOK ZILVER VENA 14X100

3 P

oin

t B

end

ing

Stif

fnes

s (N

)

Bard

Cook Optimed

Bench testing may not be

indicative of clinical

performance. Different test

methods may yield different

results. Competitive testing

samples represent

commercially available venous

stents with CE mark as of June

2014.

Bard N=20

Optimed Sinus Venous N=3

Cook Zilver Vena N=3

This product is not available for sale in the US

Stent options !

Boston

Wallstent Optimed

Cook

Zilver Vena Veniti Vici

Optimed

Sinus

obliquus

Bard

Venovo

VIVO (EU) Trial VIRTUS Trial

VERNACULARTrial Sinus Obliquus-01-NIS

Upcoming: Medtronic, Gore, ab Medica, INTACT, Abbott Vascular

Results from VIVO-EU, a Prospective Study of

the Zilver® VenaTM Venous Stent in the Treatment

of Symptomatic Iliofemoral Outflow Obstruction

Michael Lichtenberg, M.D. and

Jennifer McCann-Brown, Ph.D., RAC

1Klinikum Arnsberg, Germany; 2Cook Research Incorporated

On behalf of the Investigators:

Christoph Binkert, M.D.

Narayan Karunanithy, M.D.

Michael Lichtenberg, M.D.

Marta Ramirez Ortega, M.D.

15

Real World Patient Population

16

Medical History Reported

(N=35)

Clotting disorder (family history) 14.3% (5)

Bleeding diathesis/coagulopathy 14.3% (5)

Pulmonary embolism (history or current)

20.0% (7)

Deep vein thrombosis (DVT) 62.9% (22)

Acute DVT Acute DVT on Chronic DVT

Chronic DVT

40.9% (9/22) 9.1% (2/22)

50.0% (11/22)

DVT (family history) 28.6% (10)

History of cancer 8.6% (3)

Currently undergoing treatment 33.3% (1/3)

Acute DVT Acute DVT on Chronic DVT

Chronic DVT

40.9% (9/22) 9.1% (2/22)

50.0% (11/22)

Baseline Lesion Data

17

Vessel location(s) Site Reported

(n=35) Core Lab

(n=34)

Side treated

Left

Right

94.3% (33)

5.7% (2)

94.1% (32)

5.9% (2)

Lesion Location

Common iliac vein 57.1% (20) 55.9% (19)

External iliac, common iliac veins 22.9% (8) 14.7% (5)

Common femoral, external iliac, common iliac

veins 20.0% (7) 20.6% (7)

Common femoral vein 0% (0) 5.9% (2)

Femoral, common femoral, external iliac,

common iliac veins 0% (0) 2.9% (1)

Lesion Characteristics

Lesion Length (mm; Mean ± SD) 106 ± 69 (n=35)

(range: 20-256 mm)

89.3 ±58.6 mm (n=31)

(range: 5.6-219.9)

Total Occlusion 12.9% (4/31)1 22.6% (7/31)

Lesion data are consistent with previous reports for this population.

1A determination of total occlusion could not be made in four patients. .

Major Adverse Events

Major Adverse Event Frequency (n=35)

Procedural bleeding requiring transfusion 0

Procedure- or device-related death 0

Clinically-driven target lesion reintervention for occlusion1 1

Stent migration requiring intervention 0

Procedure- or device-related symptomatic pulmonary embolism2 1

Procedure-related uncorrectable perforation 0

Procedure-related flow-limiting dissection of the target vessel 0

Total 2

1 A clinically-driven reintervention for occlusion at 155 days post-procedure. Edema and a pre-reintervention INR of 1.1; the occlusion was treated by thrombolysis, balloon angioplasty, and additional stent placement.

2 A symptomatic pulmonary embolism one day post-procedure, categorized as possibly related to the study procedure and managed by a change in medication. No additional clinical sequelae reported.

18

Venous Clinical Severity Score Improved Following Treatment

19

Four patients did not complete 12-month follow-up due to unrelated death (n=1), withdrawal (n=1), or lost-to-follow-up (n=2). Patients with any reintervention (n=5) in the stented vessel were excluded from subsequent assessment of venous clinical symptoms.

VICI 14 x 120 mm

VIRTUS Feasibility Trial Design

Objective Assess safety & effectiveness in achieving patency of target venous lesion through 12-M post stent placement

Safety MAEs @ 30 days

Effectiveness Primary Patency @ 12-M

Principal Investigators

Dr. William Marston Dr. Mahmood Razavi

Study Design Prospective, multicenter, single arm non-randomized, up to 45 sites worldwide

Patient Population

200 subjects with clinically significant chronic non-malignant obstruction of the iliofemoral venous segment – first 30 were feasibility.

Etiologies: Post Thrombotic (75%); Non Thrombotic (25%)

Core Labs

Venography: Syntactx IVUS: St. Lukes DUS: VasCore/MGH X-Ray: Syntactx

Non-thrombotic

Post-thrombotic

Image Courtesy of Mr. Stephen Black

Image Courtesy of Mr. Mahmood Razavi

Demographics & Medical History Female 24 (80%) Male 6 (20%)

Age 44.4 ±14.1 years

CEAP* Baseline

0 3% (pain by VCSS Score of ≥2)

1 0%

2 0%

3 47%

4 40%

5 7%

6 3%

Etiology

PTS 63%

NIVL 37%

Target Lesion Location

Lesion1 Location

Patients N = 30

Left N = 25 (83%)

Right N = 5 (17%)

CIV lesions 26/30 (87%)

EIV lesions 18/30 (60%)

CIV & EIV lesions 15/30 (50%)

Lesions that extended into CFV2

9/30 (30%)

Average Target Lesion Length

11.9 ±6.7 cm

1. Some patients have more than 1 lesion or lesion extends in multiple vein segments 2. No lesions were isolated to the CFV alone

Patency by Duplex Ultrasound (Corelab Analysis)

Courtesy of Dr. Ediberto Soto-Cora

Patency Results of Feasibility Cohort (N=30)

Primary Patency1 Secondary

Patency

1- M 93% 100%

6 – M 90% 100%

12 – M 93% 97%

Patency Results at 12-Months (Site Reported)

Primary Patency1

Secondary Patency

Full Cohort (N=30) 87%

(26/30) 97%

(29/30)

Etiology

NIVL 37% 100% (11/11) 100% (11/11)

PTS 63% 79% (15/19) 95% (18/19)

All patients enrolled in the study will be followed until study completion

Patency by Lesion Etiology (Site Reported)

Courtesy by Dr Michael Sadek

Safety Endpoint Results

Primary Safety Endpoint through 30 Days (n=30)

n %

Composite Major Adverse Events (MAE) 0 0

Device or procedure-related death 0 0

Device or procedure-related bleeding 0 0

Device or procedure-related vessel injury 0 0

Device or procedure-related DVT (non-target vessel segment)*

0 0

Clinically significant PE 0 0

Embolization of stent 0 0

No MAEs @ 30 days

VCSS Pain Scale

45% had “substantial symptomatic improvement” (VCSS ≥2 ) @12-M

CIVIQ-20

Arnsberg Venous Registry VENITI VICI VENOUS STENT® System

Objective Assess safety & effectiveness in achieving patency of target venous lesion through 36 months post stent placement (VENITI VICI Stent)

Effectiveness Primary Patency @ 12-M

Principle Investigators Dr. Michael Lichtenberg Dr. Rick de Graaf

Study Design Ongoing prospective, single arm, single center non-randomized registry FU 1 (4 weeks), FU 2 (6 months), FU 3 (12 months), FU 4 (24 months), FU 5 (36 months)

Patient Population Subjects with clinically significant chronic non-malignant obstruction of the iliofemoral venous segment

Demographics N=90

Age in years (mean ± SD [range])

57.4 ± 16.4 [19-84]

Gender Male Female

47.8% (N=43) 52.2% (N=47)

Ethnicity Caucasian

100% (N=90)

Medical history N=90

Coagulation disorder 4.4% (N=4)

Pulmonary embolism 24.4% (N=22)

Deep vein thrombosis 47.8% (N=43)

History of cancer 14.4% (N=13)

Lesion analysis N=90

Sides treated Both Left Right

7.8% (N=7) 74.4% (N=67) 17.8% (N=16)

Lesion location(s)

Left: Common iliac vein External iliac vein Common femoral vein Common iliac vein, external iliac vein Common iliac vein, external iliac vein, common femoral vein External iliac vein, common femoral vein Right: Common femoral vein Common iliac vein External iliac vein Common iliac vein, external iliac vein Common iliac vein, external iliac vein, common femoral vein External iliac vein, common femoral vein Both: External iliac (R), common iliac (L) vein External iliac (R), common iliac (L), external iliac (L) vein Common iliac (R+L), external iliac (L) vein Common iliac (R+L), external iliac (R+L), common femoral (L) vein Common iliac (R+L), external iliac (R+L), common femoral (R+L) vein

37.8% (N=34) 4.4% (N=4) 2.2% (N=2) 17.8% (N=16) 8.9% (N=8) 3.3% (N=3) 2.2% (N=2) 3.3% (N=3) 6.7% (N=6) 1.1% (N=1) 1.1% (N=1) 3.3% (N=3) 1.1% (N=1) 2.2% (N=2) 2.2% (N=2) 1.1% (N=1) 1.1% (N=1)

64 / 90 (71%) patients: Postthrombotic

26 / 90 (29%) patients: NIVL

Effectiveness analysis

0

10

20

30

40

50

60

70

80

90

100

FU 4 w FU 6 mo FU 12 mo

% Patentcy analysis

NIVL PTS

N=50 N=82 N=21

100 % 100 % 100 %

97% 90 % 87 %

9,2

5,4 4,9

4,2

0

2

4

6

8

10

12

14

Baseline FU1 FU2 FU3

Mean VCSS score (±SD)

N=90 N=82 N=50 N=21

9.2

5.4 4.9

4.2

Claudication, Pain, Swelling,

Ulceration improvemnt

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

5

Baseline FU1 FU2 FU3

Mean CEAP score (±SD)

N=90 N=82 N=50 N=21

3.6

2.6 2.7

2.4

Conclusions

• Initial 6 and 12-Month efficacy data in the VIRTUS Trial and

Arnsberg Registry are better than reported data: NIVL PTS Primary patency: 100% 87% Secondary Patency: 100% 97%

• Safety data is positive

• Patients feel substantially better

85% of population showed symptomatic improvement after venous stenting (VCSS ≥2) at 12-Months

45% had “substantial symptomatic improvement” (VCSS ≥2 ) at 12-M

• Venous anatomy and disease require dedicated venous stents

35

• Use dedicated venous stent !

• Choose wisely - based on lesion morphology

• Choose wisely – based on stent technology

• More prospective data is needed

Take home message