Update on SAVAL Tibial Stent Trial

Fadi A. Saab, MD, FACC, FSCAI, FASE

Advanced Cardiac & Vascular Centers for Amputation Prevention

Grand Rapids, MI

Clinical Associate Professor of Medicine

Michigan State University College of Human Medicine

E. Lansing, MI

Disclosures

• BD/Bard Peripheral Vascular - Consultant

• Boston Scientific – Consultant, Research

• Cardiovascular Systems, Inc.

• Cardioflow - Research

• Medtronic - Consultant

• Philips - Consultant

• PQ Bypass - Research

• Terumo - Consultant

Ankle joint

Proximal tibials

Non balloon expandableDES zone

Distal tibials

Balloon expandable DES zone

Non balloon expandableDES zonePedal arteries

The Value of Accurate Sizing

• Ultrasound, or IVUS, MUST be added to every BTK RCT to measure the true target lumen before the final therapy is delivered to:– Avoid under-sizing

– Prevent drug embolization

– Visualize the calcium distribution and proper vessel prep prior to DCB

A

B

Mustapha JA, F. Saab, MD. Drug-Coated Balloon Angioplasty for the Treatment of Calcified Tibial Vessels. CLI Global Compendium. September 2015, p. 12.

-An example of undersized DCB in the mid to distal tibialartery.

-Significant wall to balloondistance >1mm opposition.Mismatch

-Balloon expandable stent/DES will not sustain thenatural hostile environmentof this location

-That will lead us to start thinking of mandatingimage-guided DCBor a self expanding stentwith drug elution.

Example of Under-Sizing and Drug Embolization

Final angiogram should show the following:• Brisk flow in the treated artery• No loss of its pedal distribution

branches• Blush grade III at the ischemic

skin site• Foot blush and “early” venous

return

Ankle joint

Proximal tibials

Non balloon expandableDES zone

Distal tibials

Balloon expandable DES zone

Non balloon expandableDES zonePedal arteries

BTK/BTA Scaffold

The Case for DES Below-the-Knee

• Calcification not an impediment for drug delivery via DES• CTOs, long lesions, and vessel recoil favor scaffold

At least four RCTs have shown efficacy of coronary DES in BTK vessels

Two RCTs with DCB below-the-knee have not shown efficacy

Cost considerations likely to favor PTA + BTK scaffold (versus PTA + ATHX + DCB + potential bailout)

Disease State Implications

Clinical Data

Cost

DES Below-the-KneeRutherford Category & Lesion Characteristics

0%

20%

40%

60%

80%

100%

PADI DES

PADI BM

S

Stentys

DES

DESTINY D

ES

DESTINY BM

S

PREVENT DES

YUKON BM

S

YUKON DES

DESTINY 2 D

ES

ACHILLES D

ES

ACHILLES D

ES- wound

Occlusion Severe CalcificationResults from different trials are not directly comparable. Information provided for educational purposes.

0%

25%

50%

75%

100%

PaRADISE D

ES

PADI DES

PADI BM

S

DESTINY 2 D

ES

DESTINY BM

S

Etna Regist

ry D

ES

PREVENT DES

DESTINY D

ES

Stentys

DES

YUKON DES

YUKON BM

S

Rutherford Distribution

2 3 4 5 6

PADI- Spreen MI, et al. Circ Cardiovasc Interv. 2016;9(2):e002376.DESTINY- Bosiers M, et al. J Vasc Surg. 2012;55(2):390-8.YUKON- Rastan A, et al. Eur Heart J. 2011;32(18):2274-81.ACHILLES- Scheinert D, et al. J Am Coll Cardiol. 2012;60(22):2290-5. ACHILLES wound- Katsanos K, et al. JACC Cardiovasc Interv. 2016;9(3):259-67.PaRADISE- Feiring AJ, et al. J Am Coll Cardiol. 2010;55(15):1580-9.

Stentys- Bosiers M, et al. J Endovasc Ther. 2017;24(3):311-316. Etna Registry- Giaquinta A, et al. Vasc Endovascular Surg. 2017;51(2):60-66.DESTINY 2- Bosiers MJ, et al. J Cardiovasc Surg (Torino). 2017;58(1):49-54.PREVENT- Bosiers M, LINC 2016.

PADI DESTINY YUKONACHILLES PaRADISE PES-BTK-70 Etna Registry DESTINY 2 PREVENT

DES BMS DES BMS DES BMSMajor Amputation 11.4% 20.5% 1.4% 3.0% 3.2% 6.4% 13.8% 5.7% 1.5% 7.0% 3.4% 0.0%Survival 76.7% 74.9% 82.0% 84.0% 82.9% 86.1% 89.9% 87.0% 89.4% 88.1% 89.3% 88.1%

DES Below-the-Knee12-Month Results

PADI- Spreen MI, et al. Circ Cardiovasc Interv. 2016;9(2):e002376.DESTINY- Bosiers M, et al. J Vasc Surg. 2012;55(2):390-8.

YUKON- Rastan A, et al. Eur Heart J. 2011;32(18):2274-81.ACHILLES- Scheinert D, et al. J Am Coll Cardiol. 2012;60(22):2290-5.

0%

20%

40%

60%

80%

100%

DESTINY D

ES

DESTINY BM

S

YUKON DES

- all

YUKON BM

S- all

YUKON DES

- CLI

ACHILLES D

ES

ACHILLES D

ES- wound

PES-BTK-7

0

Etna Regist

ry

DESTINY 2 D

ES

PREVENT DES

Primary Patency

Freedom from TLR

Freedom from BinaryRestenosis

Note: Closed markers indicate DES group values. Open markers indicate control BMS group values.

Results from different trials are not directly comparable. Information provided for educational purposes.

Stentys- Bosiers M, et al. J Endovasc Ther. 2017;24(3):311-316. Etna Registry- Giaquinta A, et al. Vasc Endovascular Surg. 2017;51(2):60-66.DESTINY 2- Bosiers MJ, et al. J Cardiovasc Surg (Torino). 2017;58(1):49-54.PREVENT- Bosiers M, LINC 2016.

ACHILLES wound- Katsanos K, et al. JACC Cardiovasc Interv. 2016;9(3):259-67.PaRADISE- Feiring AJ, et al. J Am Coll Cardiol. 2010;55(15):1580-9.

Meta-analysis of DES for Infrapopliteal Arteries“…compared with standard PTA/BMS, DES may decrease the risk of clinically driven TLR, restenosis rate, and amputation rate without any impact on mortality.”

Zhang J, Xu X, Kong J, et al.. Vasc Endovascular Surg. 2017;51:72-83.

Restenosis

Mortality

TLR

Amputation

BSC Peripheral BMS/DES Clinical Program

BMS, bare metal stent; BTK, below-the-knee; DES, drug-eluting stent; LL, long lesions; PK, pharmacokinetics; PTA, percutaneous transluminal angioplasty; RCT, randomized controlled trial; SFA, superficial femoral artery.Caution: Eluvia is an investigational device limited under US law for investigational use only. Not available for sale in the U.S.

Prospective, multicentre, single-arm, open label

N = 299 (3 year follow-up complete)

Prospective, multicentre, single-arm, open label

N= 57 (3 year follow-up complete)

Prospective, multicentre, RCT 2:1 (Eluvia : ZilverPTX)

N = 524 (including RCT, PK, LL. Enrollment Complete)

Prospective, multicentre, RCT 2:1 (Eluvia : BMS)

N = 750 (Enrolling)

Prospective, multicentre, single-arm, open label

N = 500 (Enrolling)

Prospective, multicentre, RCT 2:1 (DES BTK : PTA) & single-arm

N = 201 & N = 100

IMPERIA

L

(DES)

MAJESTI

C

(DES)

SuperNOV

A

(BMS)

EMINEN

T

(DES/BMS)REGAL

(DES)

SFA

SAVAL

(DES)

SFA

SFA

SFA

SFA

BTK

The SAVALTM Pivotal Trial

• Planned Global Pivotal Trial

• Randomized DES vs PTA

• 6 Month Primary Patency Endpoint

• FDA EAP+ Breakthrough Pathway

• First Ever EAP in Peripheral Branch of FDA

• Enrollment Start 2018

+FDA’s Expedited Access Pathway (EAP) program is intended for breakthrough medical devices that demonstrate the potential to address unmet medical needs for life threatening or irreversibly debilitating diseases.

*CAUTION: Investigational device and not available for sale in the U.S.

A Randomized Trial comparing the Drug-Eluting Stent (DES) Below the Knee (BTK) Vascular Stent System vs Percutaneous Transluminal Angioplasty (PTA) Treating Infrapopliteal Lesions inSubjects With Critical Limb Ischemia

SAVAL™ DES BTK Stent

• Nitinol Self-Expanding Stent– Flexible crush resistant scaffold

– Diameter compliant

• PTx drug coating (PBMA/PVDF)

Differentiated technology has been selected for Expedited Access Pathway (EAP) designation by FDA

*CAUTION: Investigational device and not available for sale in the U.S.

Conclusions

• Clinical studies suggest DES may be effective for treating infrapopliteal lesions and dedicated research is underway

Limitations of the DES trials

• DES trials limited to primarily focal lesions

• Stent deformation limits use in distal vessels

• Making balloon expandable DES to be a partial solution to CLI disease

Scheinert, D. (2007). Update: drug-eluting stents in tibial arteries. Endovasc. Today, 8, 71-74.

Karnabatidis, D., Katsanos, K., Spiliopoulos, S., Diamantopoulos, A., Kagadis, G. C., & Siablis, D. (2009). Incidence, anatomical location, and clinical significance of compressions and fractures in infrapopliteal balloon-expandable metal stents. Journal of Endovascular Therapy, 16(1), 15-22.

fsaab@acvcenters.comTwitter @fadisaab17

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