Evolution and challenges of ISR

How to approachSteven Kum MD CWSP

Vascular & Endovascular Surgeon

Changi General Hospital / Mount Elizabeth Novena Hospital

Singapore

DISCLOSURE

• The speaker’s presentation today is on behalf of Becton, Dickinson and Company. The physician has been compensated by Becton, Dickinson and Company to participate in this presentation.

• The opinions and clinical experiences presented herein are for informational and educational purposes only. The results presented may not be predictive for all studies and patients and may vary depending on a variety of patient specific attributes.

• This presentation is intended for this audience and educational program only. Recording, videotaping, or photography is prohibited for this training web

Calcium is probably the single most significant predictor of Interventional success

Mechanical Effects Pharmacological Effects

• Barrier to optimal dilatation

• Key cause of severe dissections and recoil

• Associated with high incidence of angiographic complications

1. Laird J et al. Twelve-Month Results From the RESILIENT Randomized Trial. Circ Cardiovasc Interv. 2010;3:267-276.2. Adams GL et al. Subanalysis of the CONFIRM Registries. J INVASIVE CARDIOL 2015;27(11):516-520.3. Roberts D. : Final Results of the DEFINITIVE Ca11 Trial. Catheteriz and Cardiovas Intervent 2014 84:236–244.

1. Fanelli F et al. Calcium Burden Assessment and Impact on Drug-Eluting Balloons in Peripheral Arterial Disease.Cardiovasc Intervent Radiol (2014) 37:898–907.

2. Tepe et al. Drug-Eluting Balloon Therapy for Femoropopliteal Occlusive Disease: Predictors of Outcome With aSpecial Emphasis on Calcium J Endovasc Ther. 2015 Oct;22(5):727-33

3. Tzafriri AR, Garcia-Polite F, Zani B, Stanley J, Muraj B, Knutson J, Kohler R, Markham P, Nikanorov A, Edelman ER.Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis. J ControlRelease. 2017 Sep 1;264:203-210

4. Tellez A, Dattilo R, Mustapha JA, Gongora CA, Hyon CM, Palmieri T, Rousselle S, Kaluza GL, Granada JF. Biologicaleffect of orbital atherectomy and adjunctive paclitaxel-coated balloon therapy on vascular healing and drugretention: early experimental insights into the familial hypercholesterolaemic swine model of femoral arterystenosis. EuroIntervention. 2014 Dec;10(8):1002-8

• May reduce absorption of drug

• Underestimated by angiography

• Highly prevalent in:• Elderlies• Diabetics• Kidney disease

STENTS WILL CONTINUE TO FUFILL A NEED

Stenting Rates in DCB registries for Claudicants are high

1Werk M et al. Circulation 2008; 2Werk et al. Circ Cardiovasc Interv 2012; 3Tepe G et al. N Engl J Med 2008; 4icari A Et al. J Am Coll Cardiol Intv

2012; 5Tepe et al. Circulation 2015; 6Zeller T et al. J Endovasc Therapy 2014; 7Schmidt A. LINC 2013; 8Schroeder H et al. Catheter CardiovascInterv 2015; 9Laird J. Endovacsular Today Feb 2015. 10Ansel G. TCT 2015.

Stenting in FP CLTI is also high

59% TASC C/D

49% Stent

58% had FP lesions

Iida O, Nakamura M, Yamauchi Y, et al.3-Year Outcomes of the OLIVE Registry, a Prospective Multicenter Study of Patients With Critical Limb Ischemia: A Prospective, Multi-Center, Three-Year Follow-Up Study on Endovascular Treatment for Infra-Inguinal Vessel in Patients With Critical Limb Ischemia. JACC Cardiovasc Interv. 2015;8(11):1493-1502. doi:10.1016/j.jcin.2015.07.005

• 314 Japanese CLTIwith infrainguinal lesions who underwent EVT December 2009 to July 2011• De novo CLTI• Rutherford 4, 5 and 6• 71% Diabetes, 52% dialysis

Contemporary Woven stents can give us good acute

results

Why do stents fail?

Poor Stent Expansion

Stent Fractures

Neointimal Hyperplasia

Acute Stent Failure Heterogenous nature of in stent occlusion

Soft acute clot in DES placed above a woven

stent filled with dense ISR

No ISR in DES

Chronic Stent Failure

“End Stage” SFA ISR –

Stent removal prior to Bypass

When is it acute or chronic?

Pathology of Stent Failure

• Acute stent thrombosis more common than we think and may have a silent presentation

• Stent fractures common

Kuntz SH, Torii S, Jinnouchi H, et al. Pathology and Multimodality Imaging of Acute and Chronic Femoral Stenting in Humans. JACC Cardiovasc Interv. 2020;13(4):418-427. doi:10.1016/j.jcin.2019.10.060

Aim of Therapeautic Approach

1. Prolong stent patency (mechanical issues, anti-restenotic therapy)

2. Preserve future options

– Future interventional options

– Future bypass options

3. Avoid collateral coverage / risks of acute limb ischemia

4. Limit costs (esp claudicants)

5. Avoid complications

– distal embolism

Options:1. POBA2. DCB alone3. DES4. Covered stent5. Debulk alone6. Debulk + DCB7. Brachytherapy8. Remote

endarterectomy9. Bypass

POBA FOR ISR –Freedom from Recurrent Restenosis

Tosaka et al. JACC 2012;59:16-23

Covered stent for ISR

Lesion length 17 cm

DES for ISR

Zeller et al, J Am Coll Cardiol Intv 2013; 6:274-281

Lesion length 13 cm

Bosiers M, Deloose K, Callaert J, et al. Superiority of stent-grafts for in-stent restenosis in the superficial femoral artery: twelve-month results from a multicenter randomized trial. J Endovasc Ther. 2015;22(1):1-10. doi:10.1177/1526602814564385

DCB alone for ISR

DCB for in stent occlusion

Feb 2011

No restenosis seen

2.5 years

DEB from P3 to SFA , no stent

Aug 2013

Rest Pain, Severe Stent Fracture

DCB seems less effective in Tosaka Class III

Virga V, Stabile E, Biamino G, Salemme L, Cioppa A, Giugliano G, Tesorio T, Cota L, Popusoi G, Pucciarelli A, Esposito G, Trimarco B, Rubino P. Drug-eluting balloons for thetreatment of the superficial femoral artery in-stent restenosis: 2-year follow-up. JACC Cardiovasc Interv. 2014 Apr;7(4):411-5

Restenosis @ 2 years based on Tosaka Class

Freedom from TLR @ 3 years based on Tosaka Class

Grotti S, Liistro F, Angioli P, Ducci K, Falsini G, Porto I, Ricci L, Ventoruzzo G, Turini F, Bellandi G, Bolognese L. Paclitaxel-Eluting Balloon vs Standard Angioplasty to ReduceRestenosis in Diabetic Patients With In-Stent Restenosis of the Superficial Femoral and Proximal Popliteal Arteries: Three-Year Results of the DEBATE-ISR Study. J EndovascTher. 2015 Oct 28

DCB - late catch up at 3 years

Grotti S, Liistro F, Angioli P, Ducci K, Falsini G, Porto I, Ricci L, Ventoruzzo G, Turini F, Bellandi G, Bolognese L. Paclitaxel-Eluting Balloon vs Standard Angioplasty to ReduceRestenosis in Diabetic Patients With In-Stent Restenosis of the Superficial Femoral and Proximal Popliteal Arteries: Three-Year Results of the DEBATE-ISR Study. J EndovascTher. 2015 Oct 28

Why are DCBs alone less effective in Tosaka Class III ISR??

Courtesy Vermani

DCBs work by physical followed by chemical transfer into the wall.

Is organized thrombus in an occluded ISR a barrier?

Potential Benefits of Debulking in ISR

1. Improve lumen gain by removing NIH

2. Remove acute clot component

3. Reducing risk of distal embolism

4. Improve drug absorption

Courtesy Shammas LINC 2016

Debulking alone is not enough

Combination Laser Debulking and DCB

Gandini R, Del Giudice C, Merolla S, Morosetti D, Pampana E, Simonetti G. Treatment of chronic SFA in-stent occlusion with combined laser atherectomy and drug-elutingballoon angioplasty in patients with critical limb ischemia: a single-center, prospective, randomized study. J Endovasc Ther. 2013 Dec;20(6):805-14*Stellarex DCB is not currently approved for use in SFA ISR

Primary Patency @ 12 months60% DCB vs 40% POBA

Combination Laser Debulking and DCB

Kokkinidis DG, et al. Laser Atherectomy Combined With Drug-Coated Balloon Angioplasty Is Associated With Improved 1-Year Outcomes for Treatment of Femoropopliteal In-Stent Restenosis. J Endovasc Ther. 2018 Feb;25(1):81-88.

• “Real world” analysis of treatment of FP-ISR withlaser + DCB (n=62) vs laser + PTA (n=50).• Retrospective analysis, two centers• N=112• 33% CLI• 74% Tosaka III• Average Lesion Length 247 ± 115 mm

Freedom from Occlusion @ 12 months86% Laser + DCB vs 57% Laser + POBA

Intervention Feature

- Native „virgin“ arteries

- Surgical bypasses

- Redo procedures

- In-stent procedures

Rotational Debulking:The Leipzig experience in 1.800+ patients

338 Procedures

Acute ( <14 days ) 73 (21.6%)

Subacute ( < 3 months ) 114 (33.7%)

Chronic ( > 3 months ) 151 (44.6%)

Rotational Debulking: In-stent procedures:Onset of symptoms (n=338)

Leipzig Rotational Debulking + DCB

Registry (39% ISR)

RD + DCB

DCB only

Freedom from restenosis

Days follow-up

Schmidt LINC 2013

Rotational Debulking + DCB

Loffroy R, Edriss N, Goyault G, et al. Percutaneous mechanical atherothrombectomy using the Rotarex®S device in peripheral artery in-stent restenosis or occlusion: a French retrospective multicenter study on 128 patients. Quant Imaging Med Surg. 2020;10(1):283-293. doi:10.21037/qims.2019.11.15

Liao CJ, Song SH, Li T, Zhang Y, Zhang WD. Combination of Rotarex Thrombectomy and Drug-Coated Balloon for the Treatment of Femoropopliteal Artery In-Stent Restenosis. Ann Vasc Surg. 2019;60:301-307. doi:10.1016/j.avsg.2019.02.018

• 32 patients, 80% CLTI

• 56% Tosaka Class III (ie occlusion)

• RB + Orchid DCB

• LL = 123 ± 90 cm

• 12 month PP = 86.2%

• 12 month FF CD-TLR = 89.7%

• Distal protection in 56.2% patients

• Embolism = 6.3%

• 128 patients, 52% CLTI

• 60% Tosaka III (ie occlusion)

• 22% supplementary DCB, rest PTA

• 74% SFA/pop

• LL : 23% > 10 cm long

• 12 month PP = 92.3%

• 12 month FF CD-TLR = 80.5%

• Embolism = 5.5%

Milnerowicz A, Milnerowicz A, Kuliczkowski W, Protasiewicz M. Rotational Atherectomy Plus Drug-Coated Balloon Angioplasty for the Treatment of Total In-Stent Occlusions in Iliac and InfrainguinalArteries. J Endovasc Ther. 2019;26(3):316-321. doi:10.1177/1526602819836749

• 74 patients, 50% CLTI

• 100% Tosaka Class III (ie occlusion)

• RB + DCB

• LL = 220 ± 150 cm

• 12 month PP = 79.5%

• 12 month FF CD-TLR = 94.5%

• Embolism = 8.1%

Rotational Debulking + DCB

3mm proximal predilatation only…

IVUS

Pre-RB Post-RB

Post-DEB

Rotational Debulking + DCB

Dec 2012 June 2014Patency

maintained despite poor runoff

June 2013Sep 2011RB and

IN.PACT DEBAlmost 3 years

Rotational Debulking + DCB

My Treatment Algorithmfor SFA/Pop ISR

Occlusion Stenosis

Rotational Debulking

DCB

? Atherectomy

Summary

• ISRs will continue to be a challenge to treat

• Varied clinical presentation and heterogenous pathology seen in ISR requires a mechanical and anti-restenotic solution

• Rotational Debulking + DCB shows early promise in small series and can be considered in Tosaka Class III

• Head to head studies of combination therapies should be considered