Is There Still a Controversy About Stent Type for TASC

C&D Lesions? Insights From COBEST

Randomized Trial

Aravinda Nanjundappa, MD, FACC, FSCAI

Associate Professor of Medicine and Surgery

West Virginia University

Charleston, WV

Claudication treatment options

•Treatment Benefit QOL Limitation

Exercise 100% ↑↑ Not available

Angioplasty 50-100% ↑ Distal lesions

Surgery 150% ↑↑ 　　 2-5% risk

Cilostazol 50% ↑ Not in CHF

Claudication treatment options•Treatment Mechanism TASC II

Exercise Metabolic,

Walking efficiency A

Endothelial

Angioplasty Hemodynamic A

Cilostazol Metabolic,

Hemodynamic A

Vascular smooth muscle

Results of Iliac AngioplastyResults of Iliac Angioplasty

70

75

80

85

90

95

100

Two to Four Year PatencyTwo to Four Year PatencyGruntzig (1979)

Spence (1981)

Schwarten

(1984)

Kumpe (1982)

Gallino (1982)

Gruntzig (1979)

Spence (1981)

Schwarten

(1984)

Kumpe (1982)

Gallino (1982)

%

4 Y

ear

3 Y

ear

2 Y

ear

2 Y

ear

2 Y

ear

87%87%

82%82%

89%89%87

%87%

82%82%

Results of Iliac AngioplastyResults of Iliac Angioplasty

• 667 iliac procedures analyzed

• One month clinical success 90.2%

• 667 iliac procedures analyzed

• One month clinical success 90.2%

0

10

20

30

40

50

60

70

80

Late Clinical SuccessLate Clinical SuccessLate Clinical SuccessLate Clinical Success

Ann Surg 1987;206:403-13Ann Surg 1987;206:403-13

1 Y

ear

1 Y

ear

2 Y

ears

2 Y

ears

3 Y

ears

3 Y

ears

4 Y

ears

4 Y

ears

5 Y

ears

5 Y

ears

75.275.2%

64.964.959.759.756.756.753.453.4

Cardiovasc Intervent Radiol 1992;15:291-7.Cardiovasc Intervent Radiol 1992;15:291-7.

Stenting of Iliac ArteriesMulticenter Experience

0010102020303040405050606070708080

%%

Effect on Clinical StageEffect on Clinical Stage Stage IStage IStage IIStage IIStage IIIStage IIIStage IVStage IV

Stage 0Stage 0

Before TreatmentBefore Treatment After TreatmentAfter Treatment

Cardiovasc Intervent Radiol 1992;15:291-7.Cardiovasc Intervent Radiol 1992;15:291-7.

Stenting of Iliac ArteriesMulticenter Experience

• 587 procedures in 486 patients.• 1.9 ± 1.3 stents per patient (1 - 8).• 405 patients - unilateral stents.• 81 patients - bilateral stents.• Mean follow-up: 13.3 ± 11 months (1 -

48).• 201 patients underwent angiographic

follow-up at 8.7 ± 5.7 months.

Stenting of Iliac ArteriesMulticenter Experience

• Angiographic patency (defined as < 50% stenosis within stent): 92%

• Sustained clinical benefit:– 90.9% at 1 year– 84.1% at 2 years– 68.6% at 43 months

• Diabetes and poor run off had a negative influence on the clinical outcome

• Angiographic patency (defined as < 50% stenosis within stent): 92%

• Sustained clinical benefit:– 90.9% at 1 year– 84.1% at 2 years– 68.6% at 43 months

• Diabetes and poor run off had a negative influence on the clinical outcome

Four Year Patency

53

67

4453

01020304050607080

PTA STENT

StenosisOcclusion

Radiology 1997;204:87-96Radiology 1997;204:87-96

Critical Limb IschemiaCritical Limb Ischemia

Four Year PatencyFour Year Patency

Radiology 1997;204:87-96Radiology 1997;204:87-96

ClaudicationClaudication

6577

5461

0102030405060708090

PTA STENT

StenosisOcclusion

6577

5461

0102030405060708090

PTA STENT

StenosisOcclusion

PTA vs. Stenting For Aortoiliac Occlusive Disease

• Meta-analysis of 6 PTA studies (1,300 patients) and 8 stent studies (816 patients)

• Immediate technical success:– PTA 91%– Stent 96%

• Risk of long-term failure reduced by 39% after stenting

P < 0.05P < 0.05

Radiology 1997;204:87-96Radiology 1997;204:87-96

Randomized Trial:Mean Restenosis

Randomized Trial:Mean Restenosis

612 15 1414

1923

27

0

10

20

30

40

50

60

Immediate 6 Months 12 Months 24 Months

StentPTA

G. Richter et al, 1992G. Richter et al, 1992

% L

umin

al N

arro

win

g%

Lum

inal

Nar

row

ing

• Trial Design:

A prospective, multi-center, single arm study to obtain additional data on the safety and efficacy of the Express™ LD Stent implantation in the treatment of stenosed or occlusive atherosclerotic disease (de novo or restenotic) in iliac arteries (common and/or external).

• Objective:

The objective was to demonstrate non-inferiority of the Express™ LD Stent for the treatment of atherosclerotic iliac artery lesions as compared to an objective performance criterion* (OPC), with a primary endpoint of mean percent luminal diameter loss at 6 months.

• Enrollment:

151 patients (163 lesions) with de novo or restenotic atherosclerotic lesions <100mm long in vessels between 5 and 10 mm in diameter with stenosis > 50%.

Express® LD Iliac Premounted Stent System, MELODIE Trial - Overview

90541175

*Objective Performance Criterion An objective performance criterion (OPC) is a benchmark used to compare a trial’s results against a literature derived control group. For the MELODIE study the objective performance criterion was constructed from the Palmaz® Balloon Expandable Stent iliac study, Cardiovasc Intervent Radiol 15: 291-297, 1992, and was defined as 15% mean percent luminal diameter loss at 6 months.Palmaz is a trademark of Johnson and Johnson.

Express® LD Iliac Premounted Stent SystemMELODIE Trial – TLR

6.3

9.010.2

0

2

4

6

8

10

12

6 Months 1 Year 2 Years

TLR%

90541175

Role of covered stents

• Several studies have demonstrated that PTFE covered stents may provide better results as compared to bare metal stents, particularly in TASC C and D lesions.

• Chang, et al demonstrated that covered stents show a significantly higher patency rate long term (at 5 years) as compared to bare metal stents when used to treat TASC C & D iliac lesions (87% vs. 53% p≤.01)6.

Covered stents

• Of note, the covered stent lesion characteristics were statistically more advanced than those in the bare metal group (38% of covered stent group had type C & D lesions versus 7% for BMS p=0.034).

• The covered stent group had superior outcomes, regardless of the type of lesions treated

TASC II aorto-iliac lesionsType C and Type D

Atrium’s Bx Covered StentsAdvanta™ V12 and iCAST™

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only)

Atrium’s FilmCast™ Encapsulation Technology

Stent type LengthUncoated corrugated ring (28 day) 72±23

ePTFE+corrugated ring (28 day) 18±03*

Uncoated slotted tube (28 day) 93±16

ePTFE+slotted tube (28 day) 17±04***

  Neointimal (µm)

ePTFE+slotted tube (56 day) 13±02

   

* P<0.007 compared to uncoated corrugated ring

**P<0.0001 compared to uncoated slotted tube

Rogers, C & E. Edelman. A Non-GLP Study of Biologic Responses to Uncoated and PTFE Coated Steel Stents in Rabbit Iliac Arteries. (1997)

BMS at 28 days

Covered Stent

at 28 days

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

COBEST TrialWhat is COBEST: (Covered Balloon Expandable Stent Trial)• A prospective, randomized, controlled, multi-center (12 sites) clinical trial

comparing Atrium’s balloon expandable covered stent to bare metal stents for use in iliac occlusive disease.

Inclusion criteria:• Type B, C, or D lesions.• Dissection after angioplasty.• Recurrent stenosis after angioplasty.

Follow up:• Patients were followed clinically (with ABI and symptom relief) and by

duplex US scan at 6, 12, and 18 months.

Primary Objective:• Binary restenosis (<50% stenosis on DU/Angiogram)=primary

patency at 6, 12 and 18 months.

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

COBEST Trial-18 Month ResultsAtrium’s covered stent technology is superior to bare metal stents for iliac occlusive disease.• V12 showed lower binary restenosis rates (p=0.037).

• Binary restenosis defined as vessel patency <50% • This proves the V12 offers higher patency than bare metal stents

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

COBEST Trial-18 Month Results• V12 group experienced the greatest improvement in Type C & D lesions

• These findings are highly statistically significant (p<.002) • V12 outperforms bare metal stents with more challenging C & D lesions

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

COBEST Trial-18 Month ResultsV12 showed significantly lower target lesion revascularization Rates (TLR)

•If the patient received a bare metal stent, they were 5X more likely to need a re-intervention •This is a huge burden on a patients quality of life and an enormous economic impact on the overall health system

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

Outcomes of Kissing Covered Stents Compared to Non-Covered Stents for Aortic Bifurcation Lesions

Objective:

• Retrospective review

• Kissing Stents for aorto-iliac lesions

• Compared bare metal stents to covered stents

Methods:• 26 patients received Atrium covered stents

• 28 patients received bare metal stents– 17 patients with Palmaz Genesis (Cordis) and 11 patients with Express LD (BS)

• Median follow up was 21 months

– 25 months for the non covered stent group

– 20 months for the covered stent group

• Indications for stent placement included claudication and limb-threatening ischemia.

iCAST is FDA approved for the Sabri SS, Angle JF, Choudrhi AF, Dake MDJournal of Vascular and Interventional Radiology July 2010 treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

Outcomes of Kissing Covered Stents Compared to Non-Covered Stents for Aortic Bifurcation Lesions

Results:• Treated lesion characteristics were statistically more advanced in

the patients with covered stents:– 38% of Atrium covered stent patients had type C & D lesions

(p=0.034)– 7% of BMS patients had type C lesions– 0% of BMS patients had type D lesions– 92% of BMS patients had simple type A & B lesions

• Technical success was achieved in 100% in both groups.• Primary patency rates at 1 & 2 years:

– Bare Metal Stents = 78% and 62%– iCAST covered stents = 92% and 92% (p value = 0.023)

• ABI’s at follow up:– Covered stent group- increased from 0.74/0.61 (right/left) to

0.80/0.88– Bare metal stent group-decreased from 0.77/0.070 (right/left) to

0.74/0.79iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

Outcomes of Kissing Covered Stents Compared to Non-Covered Stents for Aortic Bifurcation Lesions

Results Continued:

• Sustained clinical improvement at follow up:

– 85% of Atrium covered stent patients had sustained clinical symptom improvement during follow up period.

– 54% of BMS patients had sustained clinical symptom improvement

• TVR at 2 years:

– Atrium Covered Stent = 8%

– BMS = 38 %

Conclusion:– There is a clinically and statistically significant difference in the

patency rates of balloon expandable covered versus bare metal balloon expandable stents employed in the treatment of atherosclerotic occlusive disease of the aortic bifurcation and proximal CIA’s.

iCAST is FDA approved for the treatment of tracheobronchial strictures. Advanta V12 is CE approved for restoring the patency of iliac and renal arteries (renal approval is for 5-7mm sizes only).

iCARUS Trial

What is iCARUS?• Atrium iCAST Iliac Stent Trial • IDE trial to support a PMA application

Objective:• To evaluate the iCAST covered stent for treating iliac

artery stenosis (as compared to other FDA approved iliac stents) in patients with de novo or restenotic lesions in the common and/or external iliac arteries.

iCARUS Trial

Study design:• Prospective, multi-center, non-randomized, single arm

registry

Primary endpoint:• A composite endpoint defined as:

• Occurrence of death with 30 days, • Target site revascularization or • Restenois within 9 months post-procedure

iCARUS TrialSecondary Endpoints:• MAVE• MAE• Device Success• Acute Procedural Success• Clinical Success• Patency• Composite rate of 30 day death, 9-month target site

revascularization and 9 month restenosis in subjects without total occlusions of the iliac

iCARUS Trial

• Clinical sites:• 25 sites in the US • 1 international site

• 165 Patients enrolled

• Enrollment:• Completed in October 2010

• 9 month follow up• Last patient scheduled for 9 month • follow up in July 2011

• PMA submission by end of 2011

Conclusions

• Covered stents are safe, less TVR and less re stenosis for patients with TASC C and D lesions

• Results of iCARUS are awaited• Cost benefit ratio of covered stent versus

BMS: Less TVR and less readmissions•