Debulking Below the Knee: Devices & Techniques Jihad A. - - PowerPoint PPT Presentation

Debulking Below the Knee: Devices & Techniques

Jihad A. Mustapha, MD, FSCAI, FACC Advanced Cardiac & Vascular Centers for Amputation Prevention Grand Rapids, MI

Disclosures

Bard Peripheral Vascular – Consultant Boston Scientific – Consultant, Scientific Advisory Board, Research CardioFlow – Equity, Research Cardiovascular Systems, Inc. – Consultant, Research Medtronic – Consultant Micromedical Solutions – Chief Medical Officer Philips – Consultant PQ Bypass – Research Reflow Medical – Chief Medical Officer Terumo - Consultant

Atherectomy Devices

Jetstream™ Atherectomy System (Boston Scientific) Peripheral Rotablator™ Rotational Atherectomy System (Boston Scientific) Diamondback 360™, Stealth 360™ Atherectomy System (Cardiovascular Systems, Inc) SilverHawk™, TurboHawk™ Plaque Excision System (Covidien) Turbo-Elite™ Laser Atherectomy Catheter (Spectranetics) Front-Cutting ü ü N/A DifferentialCutting ü ü ü N/A Active Aspiration ü Concentric Lumens ü ü ü Lesion Morphology: Calcium ü ü ü ü ü Soft/Fibrotic Plaque ü ü ü Thrombus ü ü

Sources: Endovascular Today Buyer’s Guide 2014. JETSTREAM System Brochure, Boston Scientific Website, 2014. Peripheral Rotablator product website, Boston Scientific, 2014. Diamondback 360 product website, CSI, 2014. Covidien website, Directional Atherectomy products, 2014. Turbo-Elite Laser Atherectomy Catheter Instructions for Use, May 2014.

The LACI Studies

The LACI Trial: 6 Month Results

• Laird et al
• 145 pt, 155 critical ischemic limbs
• 423 lesions
• 41%SFA, 15% Popliteal, 41% Infrapop
• 70% of Pts had combo occlusion and stenosis
• 29% Rutherford Class 4
• 71% Rutherford Class 5 or 6
• Limb salvage 92% at 6 months

DEFINITIVE LE

• Study Design and Oversight:
• Prospective, non-randomized, global study
• 800 subjects enrolled at 47 centers
• CEC and Steering Committee oversight and CEC adjudicaiton
• Angiographic and Duplex core laboratory analyses
• Inclusion Criteria
• RCC 1-6
• ≥ 50% stenosis
• Lesion lengths up to 20cm
• Reference Vessel ≥ 1.5 mm and ≤ 7.0 mm
• Exclusion Criteria
• Severe calcification
• In-stent restenosis
• Aneurysmal target vessel

Lesion Assessment

Characteristic Claudication (RCC 1-3) CLI (RCC 4-6) All Subjects (RCC 1-6) Number of Patients 598 201 799 Number of Lesions 743 279 1022 Mean Length (cm) 7.5 7.2 7.4 Baseline Stenosis (%) 73 76 74 Occlusions (%) 17 30 21 Anatomic location based on proximal edge of lesion treatment, % (N) SFA 72% (536) 48% (135) 66% (671) Popliteal 15% (114) 17% (48) 16% (162) Infrapopliteal 13% (93) 34% (96) 18% (189)

Core lab reported McKinsey JF et al JACC Interv 2014

Primary Patency in Subgroups

Subgroup Claudicants (n=743) CLI (n=279)

Patency (PSVR < 2.4) Lesion Length (cm) Patency (PSVR < 2.4) Lesion Length (cm) All (n=1022) 78% 7.5 71% 7.2 Lesion type Stenoses (n=806) 81% 6.7 73% 5.8 Occlusions (n=211) 64% 11.1 66% 10.3 Lesion Location SFA (n=671) 75% 8.1 68% 8.6 Popliteal (n=162) 77% 6.0 68% 5.4 Infrapopliteal (n=189) 90% 5.5 78% 6.0

Primary Patency in Subgroups

Subgroup Claudicants (n=743) CLI (n=279)

Patency (PSVR < 2.4) Lesion Length (cm) Patency (PSVR < 2.4) Lesion Length (cm) All (n=1022) 78% 7.5 71% 7.2 By Lesion Length < 4 cm (n=318) 81% 2.2 84% 2.3 4-9.9 cm (n=418) 83% 6.5 62% 6.6 ≥ 10 cm (n=283) 67% 14.4 65% 15.1 SFA Only By Lesion Length < 4 cm (n=184) 78% 2.3 82% 2.3 4-9.9 cm (n=253) 83% 6.5 60% 6.9 ≥ 10 cm (n=232) 65% 14.6 63% 15.5

Jetstream System Overview

Control POD Console

Over-the-Wire Approved for use with BSC 0.014” 300cm Thruway Guidewire Approved for use with Atherectomy Lubricants, such as Rotaglide

XC 2.1/3.0mm XC 2.4/3.4 mm SC 1.85mm

JETSTREAM XC Catheters JETSTREAM SC Catheters

(Tibial Sizes) (SFA & Popliteal Sizes) SC 1.6mm

Patient Characteristics

• 241 patients (258 lesions)

Overall (N=241) Age (years), mean ± SD 67.1 ± 9.8 Male 66.0% Medical History Hypertension 82.6% Hypercholesterolemia 66.8% Smoking 50.6% Heart Disease 47.7% Diabetes 41.1% Race Caucasian 80.1% African American 16.6% Native American 2.1% Other 1.2%

Lesion Characteristics

Overall (N=258 lesions) Non-Stenta (N=165 lesions) Stenta (N=93 lesions) Lesion location Superficial Femoral 75.6% 72.1% 81.7% Common Femoral 10.9% 15.2% 3.2% Popliteal 13.6% 12.7% 15.1% Lesion length, mean ± SD 16.4 ± 13.6 cm 14.1 ± 12.6 cm 20.5 ± 14.4 cm Calcium Gradeb 10.0% 10.2% 9.5% 1 16.2% 14.6% 19.0% 2 24.1% 17.8% 35.7% 3 28.2% 31.8% 21.4% 4 19.5% 21.0% 16.7% Lesion RVD, mean ± SD 5.7 ± 0.9 mm 5.5 ± 0.9 mm 5.9 ± 0.9 mm Occlusion (100% stenosis) 36.1% 28.7% 50.0% Pre-treatment stenosis estimate, mean ± SD 91.1% ± 9.8% 90.2% ± 10.0% 92.7% ± 9.4%

aPost hoc analysis of patients who received and did not receive adjunctive stents. bCalcium grading: 0= no visible calcification; 1= one individual segment of vessel calcification

representing <25% of the length of the entire segment; 2= aggregate calcification representing <50% of the segment length; 3= aggregate calcification representing >50% of the segment length; 4= dense circumferential calcification along the segment length.

Procedures

• 98.3% procedural success (≤30%

residual diameter stenosis post- procedure)

• 84 patients (35%) received

adjunctive stents

• Stent placement performed at
• perator’s discretion
• Embolic protection used in 22.4%
• f cases

Post-treatment stenosis estimate, mean ± SD Overall (N=258 lesions) Non-Stent (N=165 lesions) Stent (N=93 lesions) Post-Jetstream 44.4% ± 20.0% 38.5% ± 16.2% 54.8% ± 22.0% Post Adjunctive Treatment 9.8% ± 11.4% 11.6% ± 11.7% 6.6% ± 10.2%

Procedure time: 73.4 ± 37.5 min Total Jetstream run time: 4.7 ± 3.5 min Number of Passes Blades Down: 2.0 ± 1.5 Blades Up: 1.8 ± 1.4

Unique Mechanism of Action Preferential Sanding

• Elastic healthy tissue “gives” and is not affected by diamond grit
• Diseased tissue provides resistance and allows grit to “sand” the plaque

Compliant Tissue Diseased Tissue Diamond Grit

No detrimental effect Effective plaque removal

• 6 month data
• 124 patients for infrapopliteal revascularization (201 lesions)
• Claudicants 55%
• CLI 45%
• Treatment OA either stand alone or with adjuctive Rx

`

LIBERTY 360

• Prospective, observational, multi-center clinical study to

evaluate acute and long-term clinical, functional and economic outcomes of endovascular device intervention in patients with distal outflow peripheral arterial disease (PAD)

• No inclusion and exclusion
• Independent core laboratory analyses and adjudications
• Angiographic
• Duplex Ultrasound
• Six Minute Walk Test
• Health Economics
• Includes separate analyses for
• Claudicants
• Critical limb ischemia (RB4 and 5)
• Critical limb ischemia (RB6)

Device Usage by Lesion Balloon and/or atherectomy were preferred devices.

*Bailout stent group is a subset of Stent group. Bailout stent defined as stent placed due to an angiographic complication or sub-optimal result (>50% stenosis). Core Lab reported lesions. Patients with reported values may be less than total number of patients enrolled in each arm.

Comparison between Rutherford categories significant (p<0.05) 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Balloon Atherectomy Stent Bailout stent*

Rutherford 2-3 (N=599) Rutherford 4-5 (N=754) Rutherford 6 (N=145)

Major Adverse Events (MAEs) to 6 Months

High freedom from 6-Month Major Adverse Events (MAE), indicating even RC6 subjects can be treated with PVI.

Kaplan-Meier method used to obtain estimate of freedom from MAE. Greenwood’s method used to obtain the 95% confidence interval for the estimate. Pairwise Log-Rank P-values at 180-Days: RC2-3 vs. RC4-5, P<0.0001; RC2-3 vs. RC6, P<0.0001; RC4-5 vs. RC6, P=0.0453

Major Adverse Event defined as: v Death (within 30 days

• f the index

procedure) v Unplanned major amputation of the target limb (above the ankle) v Clinically-driven TVR (inclusive of TLR) of the target limb

499 484 450 414 589 554 479 406 99 87 67 54

30 90 180

Time to MAE (Days)

0.5 0.6 0.7 0.8 0.9 1.0

Survival Probability

2-3: Claudicants 4-5: CLI 6: CLI 6: CLI 4-5: CLI 2-3: Claudicants

Baseline Rutherford Classification

Product-Limit Survival Estimates

With Number of Subjects at Risk and 95% Confidence Limits

499 484 450 414 589 554 479 406 99 87 67 54

30 90 180

Time to MAE (Days)

0.5 0.6 0.7 0.8 0.9 1.0

Survival Probability

2-3: Claudicants 4-5: CLI 6: CLI 6: CLI 4-5: CLI 2-3: Claudicants

Baseline Rutherford Classification

+ Censored

Product-Limit Survival Estimates

With Number of Subjects at Risk and 95% Confidence Limits

6-Month Freedom from MAEs

(Point Estimate and 95% Confidence Intervals) Kaplan-Meier method used to obtain estimate of freedom from MAE. Greenwood’s method used to obtain the 95% confidence interval for the estimate.

60% 65% 70% 75% 80% 85% 90% 95% 100%

Rutherford 6 Rutherford 4-5 Rutherford 2-3 73.7% 81.2% 92.6%

At Risk 54 Events 23 Censored 22 At Risk 406 Events 102 Censored 81 At Risk 414 Events 35 Censored 50

6-Month RC2-3 vs. RC4-5 RC2-3 vs. RC6 RC4-5 vs. RC6 Hazard Ratio P Hazard Ratio P Hazard Ratio P MAE 0.40 [0.29, 0.56] <0.0001 0.26 [0.16, 0.41] <0.0001 0.63 [0.42, 0.95] 0.0271

6-Month Freedom from MAE Components

Point Estimate and 95% Confidence Intervals Kaplan-Meier method used to obtain estimate of freedom from MAE. Greenwood’s method used to obtain the 95% confidence interval for the estimate.

RC 2-3 RC 4-5 RC 6 At risk 445 485 61 Events 1 18 11 Censored 53 86 27

70% 80% 90% 100% 70% 80% 90% 100% 70% 80% 90% 100% 85.1% 95.3% 97.1% 87.1% 96.8% 99.8% 85.1% 83.1% 93.0%

For calculation of MAE rate, death capped at 30 days.

Death Major Amputation TVR RC 2-3

RC 2-3 RC 4-5 RC 6 At risk 446 498 66 Events 14 26 13 Censored 39 65 20 RC 2-3 RC 4-5 RC 6 At risk 414 411 59 Events 33 91 12 Censored 52 87 28

RC 4-5 RC 6

Cox proportional hazards model identifies no difference between any RC group/arm at 6 months.

Phoenix catheter

• 5 Fr, OTW, front cutting

atherectomy

• Rotational speed

10000RPM

• Debris withdrawn

through Archimedes screw system

• EASE trial >100

patients, 0.8% embolic events

Pantheris

• VISION trial
• 130 pts
• 55 (24 month results)
• 91.4% treated stand alone

Pantheris

• 9.6% DCB
• 5.1% stent
• 82% freedom from TLR at 24

months

DE DEFINITIVE AR Study De Desig ign

General and Angiographic Criteria Assessment Lesion severely calcified?

Guidewire passage, enrollment & Randomization

DAART*

(N = 48)

DCB

(N = 54)

Guidewire Passage & Enrollment

DAART*

(N=19)

No Yes Registry arm for severely calcified lesions created to limit bail-out stenting (and therefore variables) in randomized arm. * Directional Atherectomy + Anti-Restenotic Therapy Purpose: assess and estimate the effect of treating a vessel with directional atherectomy + DCB (DAART) compared to treatment with DCB alone

Clinical Limitations & Unmet Needs

Calcium as a Barrier Longer Lesion Length

Calcium Limits Vessel Expansion

1

Calcium May Limit Drug Effect

2

Increased lesion length is an independent predictor of decreased patency5.

European Journal of Vascular and Endovascular Surgery 44 (2012)

Baseline Lesion Characteristics

Per Core Lab

Baseline Characteristics DAART (N= 48) DCB (N = 54) p-Value* DAART Severe Ca++ Arm (N=19) Lesion Length (cm) 11.2 9.7 0.05 11.9 Diameter Stenosis 82% 85% 0.35 88% Reference vessel diameter (mm) 4.9 4.9 0.48 5.1 Minimum lumen diameter (mm) 1.0 0.8 0.34 0.7 Ca Calcification 70. 70.8% 8% 74. 74.1% 1% 0. 0.82 82 94. 94.7% 7% Se Severe calcification 25. 25.0% 0% 18. 18.5% 5% 0. 0.48 48 89. 89.5% 5% * p-value for DAART and DCB groups

Key Study Outcome at 12 Months - Angiographic Patency shows similar pattern

82.4 90.9 58.3 71.8 68.8 42.9

10 20 30 40 50 60 70 80 90 100 All Patients Lesions > 10 cm All Severe Ca++ DAART DCB

N = 34 N = 39 N = 22 N = 16 N = 24 N = 7 Results for all patients who returned for angiographic follow-up

What’s out there and what to choose?

• Several devices now available for debulking
• Critical question remains is debulking part of vessel prep “all” or

“some” of the time

• Each device has compelling data
• Some better for calcific disease
• Some better for ease of use
• There is no question that in some cases either for DCB or stenting a

debulking strategy is critical to obtain best initial and probably long- term outcomes

• Combined therapy appear compelling though not fully tested