2. Andrew J. Klein, MD, FSCAI Piedmont Heart Institute, Atlanta, GA
PAD Invasive Therapy
Andrew J. Klein, MD, FSCAI Piedmont Heart Institute, Atlanta, GA
Dmitriy N. Feldman, MD, FSCAI Weill Cornell Medical College, New York, NY

3. Objectives of Module
Review of guidelines for Endovascular Therapy (EVT) for three vascular beds:
Aorto-Iliac
Femoral-Popliteal
Infrapopliteal
Brief overview of device-specific data
SCAI AUC and device-specific guidelines for EVT options

4. Increasing EVT Interventions
National Inpatient Sample Study
Years
Endovascular interventions rose by 78% (36,692 vs. 67,248; p<0.001)
Open lower extremity bypasses decreased by 20% (68,326 vs. 54,348, p<0.001)
Decreasing number of major and minor amputations
Hong M et al. Ann Vasc Surg 2011:25:44-54

5. Symptomatic Patient Endovascular Revascularization Aorto-Iliac
Endovascular approach unless failure of EVT or AAA should be repaired
Femoral-Popliteal
Depends on type of disease (focal vs. diffuse, stenosis versus CTO), TASC class, patient risk factors and comorbidities, claudication vs. CLI, long term patency, renal function
Approach is changing with DCBs
Infra-popliteal
Medical therapy for most, unless CLI
DES consideration
COR IIB recommendation unless CLI

6. Exercise and PAD CLEVER and ERASE Trials
RCT of aorto-iliac claudicants to Endovascular Therapy (EVT) vs. Optimal Medical Therapy (OMT) vs. Supervised Exercise Therapy (SET)
At 18 months, the peak-walking time improved for both EVT and SET, but not OMT.
QOL was better for EVT compared with SET or OMT
ERASE
RCT of aorto-iliac and femoral-popliteal claudicants to EVT + SET vs. SET alone
EVT + SET had greater improvement in walking distance
and health-related QOL vs. SET alone
CONCLUSIONS
SET is an effective alternative to revascularization (Greater mean improvement in Peak walking time of 4.6min)
SET + EVT (~300 m walking distance increase over SET alone) in the presence of GDMT = best option
Murphy T et al. J Am Coll Cardiol 2015;65:999–1009.
Fakhry F et al. JAMA 2015;314:1936–1944.

7. Femoral-Popliteal Disease Exercise Therapy
IRONIC Trial (Invasive Revascularization or Not in Intermittent Claudication) trial
RCT of patients with both aorto-iliac & femoral-popliteal disease
Revascularization (endovascular or surgical, n=79) + OMT vs. OMT alone (n=79)
Demonstrated superiority of EVT + OMT with respect to onset of claudication and quality of life (QOL) outcomes compared to group treated with OMT alone
Intermittent claudication distance improved significantly in the invasive (+124 m) versus the noninvasive (+50 m) group (p=0.003)
Nordanstig J et al. Circulation 2014;130:939–947.

8. Symptomatic Patients: GUIDELINES
Endovascular Treatment
2005 ACC/AHA Guidelines
Class I
Endovascular procedures are indicated for individuals with a vocational or lifestyle- limiting disability due to intermittent claudication when clinical features suggest a reasonable likelihood of symptomatic improvement with endovascular intervention and (a) there has been an inadequate response to exercise or pharmacological therapy and/or (b) there is a very favorable risk-benefit ratio (e.g., focal aortoiliac occlusive disease). (Level of Evidence: A)
2016 ACC/AHA Guidelines
Hirsch AT, et al. ACC/AHA Guidelines for the Management of Patients with PAD 2005.
2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity Peripheral Arterial Disease

9. EVT Revascularization Based on TASC Class
Previously - surgery only for TASC C/D lesions
Today – “EVT-first” approach for most lesions
TASC A
Endovascular
Surgery
Aorto-iliac
Femoral-popliteal
TASC D
TASC II Working Group JVS January 2007

10. Aorto-Iliac Revascularization Indications
Aorto-iliac disease with symptoms
Relieve claudication
Wound healing in CLI
Improve functional status and Quality of Life (QOL)
Aorto-iliac disease without symptoms
Situations where large-bore arterial access is required for hemodynamic support devices (e.g., intra-aortic balloon pumps (IABP) or other catheter- based ventricular assist devices), for structural, valvular (e.g., TAVR), and vascular (e.g., endovascular aortic aneurysm repair (EVAR)) procedures
Klein A, Jaff M, Gray B et al. Catheter Cardiovasc Interv. 2017;90:E90–E110.

11. Complex Aorto-Iliac Disease (TASC D)
EVT is possible, safe and has durable short- and long-term patency
Japanese retrospective study of 2,096 patients
395 had TASC D lesions
2,206 TASC A-C lesions
No difference between the less complex lesions (TASC A-C) and the more complex lesions (TASC D)
5-year primary patency (77.9% vs. 77.1%, p=0.17)
Major adverse cardiovascular and limb events (30.5% vs. 33.4%, p=0.42)
Lower Procedural Success rates (91.6% vs. 99.3%, p<0.01) in TASC D vs. TASC A-C lesions
Higher complication rate (11.1% vs. 5.2%, p<0.01) in TASC D vs. TASC A- C lesions
Suzuki K et al. Angiology 2017;68:67–73.

12. Aorto-Iliac Disease Stent Selection
COBEST Trial
Randomized 168 iliac arteries (TASC B-D) to ePTFE covered stents vs. Bare metal stents (BMS)
Covered stents had lower restenosis rates vs. BMS (hazard ratio [HR], 0.35; 95% confidence interval (CI) 0.15–0.82; p<0.02).
Subgroup analysis: Lower restenosis rates in covered stents TASC C and D lesions vs. BMS (HR, 0.136; 95% CI 0.042–0.442). No difference in TASC B lesions (HR, 0.748; 95% CI 0.235–2.386).
5 year data showed improved patency at 18mo, 24 mo, 36mo and 60 mo with covered stent.
ICE Trial
660 common or external iliac lesions randomized to self-expanding stents (SE) or balloon expandable (BE) stents
At 12 months: Restenosis rates lower with SE stents
6.1% after SE vs. 14.9% after BE (p=0.006).
At 12 months: Freedom from TLR favored SE stents
97.2% with SE vs. 93.6% with BE (p=0.042)
Mwipatayi BP1 et al. J Vasc Surg. 2016 Jul;64(1):83-94
Krankenberg H et al.   JACC Cardiovasc Interv Aug 28;10(16):

13. Aorto-Iliac Intervention
Appropriate Use Criteria
Provisional or Primary stenting appropriate when vascular access required (e.g. for IABP, TAVR), with or without symptoms
Appropriate in >50% aorto-iliac stenosis or gradients at rest of ≥10 mmHg
Claudicants who fail medical/exercise therapy
All CLI (RC 4-6)
Klein AJ et al. Catheter Cardiovasc Interv. 2017;90(4):E90-E110.

14. Aorto-Iliac Intervention
Appropriate Use Criteria
Variety of Devices/Techniques are Appropriate or May Be Appropriate:
PTA
Drug coated balloons (DCB)
Bare metal stents (balloon expandable or self expanding)
Drug-eluting stents
Covered stents/grafts
Klein AJ et al. Catheter Cardiovasc Interv. 2017;90(4):E90-E110.

15. EVT in Common Femoral Artery
Registry Data
Supports EVT-first approach, 5 year f/u data on CFA stenting
79% freedom form TLR
TECCO Trial
117 pts RCT of common femoral endarderectomy vs. EVT for isolated CFA disease
1°outcome: M&M within 30 days
16 of 61 patients (26%) in the CFE group and 7 of 56 patients (12.5%) in the EVT group (odds ratio, 2.5; 95% CI, 0.9 to 6.6; p<0.05).
The mean duration of hospitalization was significantly lower in the EVT group (3.2±2.9 days 6.3±3 days; p<0.0001).
At 24-months: No difference in the sustained clinical improvement, the primary patency rate, and the target lesion and extremity revascularization rates
Goueffic Y et al. JACC Cardiovasc Interv Jul 10;10(13):
Azema L et al. J Vasc Endovasc Surg 2011;41:787– 793.

16. EVT in Common Femoral Artery
Retrospective study of 47 pts
Directional atherectomy + DCB versus DCB alone
No difference in primary patency or freedom from TLR at 12 months
Stavroulakis K et al. J Endovasc Ther 2018 Feb;25(1):92-99

17. Femoral-Popliteal Disease TASC and ACC/AHA Updates
TASC 2015 update recommends
“endovascular first” recommendation for experienced operators and teams
2016 ACC/AHA guidelines on PAD provide a class IIA recommendation (Level of Evidence B) for EVT of FP disease
CONCLUSION
“the choice of EVT as a revascularization approach for claudication due to femoral- popliteal disease should include a discussion of outcomes, addressing the risk of restenosis and repeat intervention, particularly for lesions with a poor likelihood of long-term durability”
Jaff MR et al. Catheter Cardiovasc Intervent Off J Soc Cardiac Angiogr Intervent 2015;86:611–625
Gerhard-Herman MD et al. J Am Coll Cardiol 2016;69:1465–1508

18. Femoral-Popliteal Disease Drug Coated Balloons
IN.PACT SFA (Randomized Trial of IN.PACT Admiral Drug Eluting Balloon vs. Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease) trial
RCT of DCB vs. uncoated PTA
Mean lesion length was 8.94±4.89 cm for DCB and 8.81±5.12 cm (P =0.82) for PTA
Total occlusions were present in 25.8% of the DCB and 19.5% of the PTA groups (p=0.22).
DCB group
Higher primary patency (82.2% vs. 52.4%; p<0.001) at 12 months
Low rate of clinically driven TLR (2.4% in the DCB arm vs. 20.6% in the PTA arm; p<0.001).
These benefits persisted at 24 months with higher primary patency (78.9% vs. 50.1%; p<0.001) and lower rates of clinically driven TLR (9.1% vs. 28.3%; p<0.001)
36 months: 1°patency: DCB compared with PTA: 69.5% versus 45.1%; log rank p<0.001); CD- TLR DCB 15.2% vs. PTA 31.1% (p=0.002)
Tepe G et al. Circulation 2015;131:495–502.
Laird JR et al. J Am Coll Cardiol 2015;66:2329–38
Schneider P et al. Circ Cardiovasc Interv. 2018;11:e DOI: /CIRCINTERVENTIONS

19. Femoral-Popliteal Disease Drug Coated Balloons
IN.PACT SFA 36 month Results
Schneider P et al. Circ Cardiovasc Interv. 2018;11:e

20. Femoral-Popliteal Disease Drug Coated Balloons
LEVANT Trials (LUTONIX DCB)
Lower-dose, paclitaxel DCB (Lutonix, Bard, Tempe, AZ).
Improved patency at 12 months vs. PTA alone (65.2% vs. 52.6%; p=0.02).
Freedom from primary safety events was 83.9% with DCB and 79.0% with uncoated PTA (p= for non-inferiority).
Rosenfield K et al. N Engl J Med 2015;373:

21. Femoropopliteal Disease Drug Coated Balloons
ILLUMENATE Pivotal Study (STELLAREX DCB)
RCT (RC 2–4) pts with DCB (n=200) vs. PTA (n=100).
1°safety end point: Freedom from device- and procedure-related death through 30 days + Freedom from target limb major amputation and CD-TLR at 12 months
92.1% for DCB versus 83.2% for PTA, p=0.025 for superiority
CD TLR DCB cohort (7.9% versus 16.8%, p=0.023)
1°effectiveness end point: 1° patency at 12 months
76.3% for DCB versus 57.6% for PTA, p=0.003
Krishnan P et al. Circulation 2017;136:

22. Femoral-Popliteal Disease Drug-Eluting Stents
ZILVER PTX Trial
5 Year Results
2 stage randomization with initial randomization to DES (n=236) or PTA (n=238).
Patients who were initially randomized to PTA (n=238) and experienced flow-limiting dissections and/or recoil requiring stenting then were secondarily randomized to provisional BMS (n=59) or DES (n=61).
The remaining 118 patients (not randomized to DES or BMS) were in the standard care group
At 5 years, DES showed a significant clinical benefit compared to PTA alone for freedom from persistent or worsening symptoms of ischemia
Yokoi H, JACC Cardiovasc Intervent 2016; 8;271–277.
Dake MD et al. Circulation 2016;133:1472–1483

23. Femoral-Popliteal Disease Atherectomy
Excisional versus Ablative
Several options, but no comparative efficacy data
Registry-based, no RCTs
Increased risk of distal embolization with these devices
Limited data to date using atherectomy + DCB
Expensive

24. SCAI Consensus Guidelines for Device Selection in Femoral-Popliteal Arterial Interventions
Feldman DN et al. Catheter Cardiovasc Interv In Press.

25. SCAI Consensus Guidelines for Device Selection in FP PVI Device Selection as DEFINITIVE Therapy
Feldman DN et al. Catheter Cardiovasc Interv In Press.

26. SCAI Consensus Guidelines for Device Selection in FP PVI Device Selection as ADJUNCTIVE Therapy
Feldman DN et al. Catheter Cardiovasc Interv In Press.

27. SCAI Consensus Guidelines for Device Selection in FP PVI
Sample Algorithm for Treating FOCAL SFA Disease
Based on Feldman DN et al. Catheter Cardiovasc Interv In Press.

28. SCAI Consensus Guidelines for Device Selection in FP PVI
Sample Algorithm for Treating DIFFUSE SFA Disease
Based on Feldman DN et al. Catheter Cardiovasc Interv In Press.

29. Femoral-Popliteal Revascularization
Appropriate Use Criteria
Variety of options are Appropriate or May Be Appropriate, including:
PTA for focal lesions, DCB, BMS or DES
Atherectomy only for undilatable lesions

30. Infra-popliteal Revascularization
Generally limited to Critical Limb Ischemia (CLI) patients
Small vessels, diffuse and long disease, high rates of restenosis
Intervention to provide straight line flow to the foot, angiosome- based approach
For claudicants, only moderate to severe (>50% diameter stenosis) lesions and multivessel tibial disease (2 tibial vessels) should be considered for revascularization.
Prior to considering infra-popliteal intervention, all hemodynamically significant inflow disease should be treated to normalize inflow to the infra-popliteal circulation.

31. New TASC Guidelines for Infra-popliteal Disease
Jaff MR, et al. . Catheter Cardiovasc
Intervent 2015;86:611–625.

32. Infra-popliteal Revascularization ACC Guidelines
“The usefulness of endovascular procedures as a revascularization option for patients with claudication due to isolated infra-popliteal artery disease is unknown”
Gerhard-Herman MD et al. J Am Coll Cardiol 2016;69:1465–1508.

33. Infra-popliteal Revascularization Drug-eluting stents
5 trials of DES, BMS, DCB
Improved patency rates with DES versus BMS, but no change with respect to limb outcomes
Consider DES for short lesions or flow-limiting dissections
ACHILLES: Scheinert D Am Coll Cardiol 2012;60:2290–2295.
DESTINY: Bosiers M et al. J Vasc Surg 2012;55:390–398.
YUKON: Rastan A et al. J Am Coll Cardiol 2012;60:587–591.
IDEAS: Siablis D et al. JACC Cardiovasc Interv 2014;7:1048–1056
INPACT DEEP: Zeller T,. J Am Coll Cardiol 2014;64: 1568–76

34. Infra-popliteal Revascularization Drug Coated Balloons
In.Pact Deep CLI trial
358 CLI pts 2:1 to DCB vs. PTA
1° efficacy endpoints at 12-month
Late lumen loss: DCB (0.61±0.78 mm) vs. PTA (0.62±0.78, p=0.95)
Clinically driven TLR: DCB 17.7% vs. PTA 15.8%, p=0.66)
Non-significant trend toward higher amputation with DCB (8.8%) compared to the PTA group (3.6%, p=0.08)
In.Pact Amphirion withdrawn from market
Zeller T,. J Am Coll Cardiol 2014;64: 1568–76

35. Infra-popliteal Revascularization
Appropriate Use Criteria
Variety of options including:
PTA for most BTK lesions
DES for complex lesions or dissections

36. CLI Patient Revascularization
2016 AHA/ACC Guideline on the Management of Patients with Lower Extremity Peripheral Arterial Disease

37. CLI Goals of Therapy
Goals of therapy for CLI (Rutherford 4–6) with infra-popliteal arterial disease include:
Relieving pain
Healing ulcerations
Preventing major amputation
Improving patient’s QOL
Prolonging survival
Gray BH Catheter Cardiovasc Intervent 2014;84:539–545.

38. Infra-popliteal Revascularization Angiosome-Guided Approach
Angiosome = vascular territory supplied by a specific source artery
This concept is based on areas of the foot (angiosomes) identified by injection of dye into cadaveric lower limbs without arterial insufficiency
Value of angiosome-guided revascularization currently unclear
Kawarada O et al. Catheter Cardiovasc Intervent 2011;78:1051–1058.
Azuma N et al. Eur J Vasc Endovasc Surg 2012;43:322–328.
Alexandrescu V et al. Scand J Surg 2012;101:125–131.
Shishehbor MH. Clev Clin J Med. 2014;81: