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Open Questions
• Can we reproduce the positive experience with DCB also in real world applications with longer and more complex lesions?
• What is the respective place of DCB and DES in different lesion subsets?
• Above the Knee / Below the Knee?
• Can vessel preparation followed by DCB provide an effective solution for more complex and calcified lesion subsets?
Clearing a Path for the Effective Treatment of Complex Arterial and Venous Disease
An Open Toolbox and Open Questions:
Where are we in Europe with Drug Elution, Atherectomy
and Thrombectomy in 2015? Prof. Dr. Dierk Scheinertert, MD
Universitätsklinikum, Leipzig
• IMPORTANT INFORMATION: These materials are intended to describe common clinical considerations and procedural steps for the on-label use of referenced technologies as well as current standards of care for certain conditions. Of course, patients and their medical circumstances vary, so the clinical considerations and procedural steps described may not be appropriate for every patient or case. As always, decisions surrounding patient care depend on the physician’s professional judgment in light of all available information for the case at hand.
• Boston Scientific (BSC) does not promote or encourage the use of its devices outside their approved labeling.
• The presenter’s experience with BSC products may not be interpreted or relied upon to support clinical claims about BSC devices or product comparison claims regarding BSC and competitive devices. The experiences of other users may vary.
• Longer lesions are associated with poorer PTA and BMS outcomes, even in predominately TASC A and B classifications
Lesion Complexity Affects Outcomes
Bosiers M, LINC 2014.
TASC A and B Lesions
Can Lesion Complexity be Mitigated by Technologies?
Drug Elution
• DCBs seem to have a positive effect in short lesions
Lesion Complexity and Drug-Eluting Technologies
Bosiers M, LINC 2014.
TASC A and B Lesions
Lesion Complexity and Drug-Eluting Technologies
• DCBs seem to have a positive effect in short lesions, but longer/more complex lesions have not been included in trials to date – DCB trial/registry patients represent population with less-complex lesions1-7
• Primarily TASC A/B, lesion length <10 cm • Less calcification
RCT Registry
FemPac1 THUNDER2 PACIFIER3 LEVANT I4 LEVANT II5
IN.PACT SFA6
Italian Registry7
N (DCB arm) 45 48 44 49 316 220 105
Mean lesion length (cm)
4.0 (median)
7.5 7.0 8.1 6.3 8.9 7.6
Calcified
53% 50% 64% severe excluded
59% 8% 50% moderate 17% severe
Total occlusion
13% 27% 23% 41% 21% 26% 30%
1. Werk M, et al. Circulation. 2008;118:1358-1365. 2. Tepe G, et al. N Engl J Med. 2008;358:689-699. 3. Werk M, et al. Circ Cardiovasc Interv. 2012;5:831-840. 4. Scheinert D, et al. JACC Cardiovasc Interv. 2014;7:10-19. 5. Rosenfield K. TCT 2014. 6. Tepe G, et al. Circulation. 2014; Epub ahead of print. 7. Micari A, et al. JACC Cardiovasc Interv. 2013;6:282-289.
• DCBs seem to have a positive effect in short lesions, but longer/more complex lesions have not been included in trials to date – DCB trial/registry patients represent population with less-complex lesions1-7
• Primarily TASC A/B, lesion length <10 cm • Less calcification
– DCB effect in lesions ≥10 cm investigated in one retrospective study8 • 12-month TLR rate within the range reported in shorter-lesion trials
Lesion Complexity and Drug-Eluting Technologies
1. Werk M, et al. Circulation. 2008;118:1358-1365. 2. Tepe G, et al. N Engl J Med. 2008;358:689-699. 3. Werk M, et al. Circ Cardiovasc Interv. 2012;5:831-840. 4. Scheinert D, et al. JACC Cardiovasc Interv. 2014;7:10-19. 5. Rosenfield K. TCT 2014. 6. Tepe G, et al. Circulation. 2014; Epub ahead of print. 7. Micari A, et al. JACC Cardiovasc Interv. 2013;6:282-289. 8. Zeller T, et al. J Endovasc Ther. 2014;21:359-368.
0%
10%
20%
30%
FemPac LEVANT II PACIFIER THUNDER LEVANT I IN.PACT SFA Zeller et al(2014)
12-month TLR Rate
Mean lesion length
<10 cm ≥10 cm
IN.PACT SFA Trial Clinically-driven TLR
ABI decrease >0.15 or ≥20%, or symptoms 12-Month Primary Patency
(Clinically-driven TLR, PSVR >2.4)
• Randomized, controlled study of DCB vs PTA in the SFA and/or proximal popliteal artery • Key Exclusion Criteria
• Aneurysm or thrombus within the target vessel • Angiographic evidence of severe calcification • Mandatory pre-randomization pre-dilatation results in a major (≥Grade D) flow-limiting
dissection or residual stenosis >70% and translesional peak gradient >10mm Hg
Tepe G. Charing Cross, 2014. Schneider P. TCT 2014. Tepe G, et al. Circulation. 2014; Epub ahead of print.
DCB for PAD: A look ahead
0
50
100
150
200
250
300
350
2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
Mar
ket
Re
ven
ue
($
m)
Year
Infrapoplitealartery
Femoropoplitealartery
Iliac artery
The larger market size for femoropopliteal and infrapopliteal arteries is attributed to the feasibility of using DCB as a primary or alternative therapy in those vessels and the use of multiple DCB per procedure (~1-2 DCB/procedure)
Global* DCB Market for treating PAD in the lower extremity ($m), 2010–2019
GlobalData. MediPoint: Drug-Eluting Balloons – Global Analysis and Market Forecasts. Sep 2013
*US, France, Germany, Italy, Spain, UK, Japan, China, India, Brazil
Company Device Drug Coating Dose Density
(μg/mm2) CE Marked
Aachen-Resonance Elutax PTx (no carrier) 2
B. Braun SeQuent Please PTx – Iopromide
Paccocath Technology 3
Bard-Lutonix MOXY PTx – Polysorbate/Sorbitol 2
Biotronik Passeo-18 Lux PTx – BTHC
Butyryl-tri-hexyl-Citrate 3
Boston Scientific Ranger PTx – Acetyl Tributyl Citrate
Transpax Technology 2
Cook Medical Advance 18 PTx PTx (no carrier) 3
Eurocor Freeway Series PTx – Shellac 3
Medtronic Cotavance PTx – Iopromide
Paccocath Technology 3
Medtronic IN.PACT Series
(Admiral, Pacific) PTx – Urea (FreePac)
3
Medtronic (Covidien) Stellarex PTx - ? 2 NO
BSC Data on File. Zeller, T. TCT 2014.
Peripheral Drug-Coated Balloons
• CE-mark received July 2014 • Sterling balloon platform • TransPax coating technology
(Paclitaxel) • Ranger Loading Tool
– Designed to protect the drug coating
• 5F-compatible • Compatible with 0.035 guidewires • Size matrix:
– SFA: 4-8 mm; 40-100 mm – BTK: 2-4 mm; up to 150 mm
Ranger Drug-Coated Balloon
Ranger is an investigational device not for sale in the U.S.
Clinical Study Overview: Ranger
Name Ranger DCB
Objective To prove the superior performance of the Ranger™ paclitaxel-coated PTA balloon catheter for angioplasty for femoropopliteal artery lesions when compared to non-coated balloons at six months post-procedure when comparing Late Lumen Loss (LLL).
Study Design Prospective, randomized, multicenter, controlled trial (2:1 Ranger DCB vs. uncoated balloon)
Subjects 105 patients with femoropopliteal artery lesions
Investigational Centers
11 sites (Germany, France, and Austria)
Primary Endpoint Primary patency at 6 months post-procedure assessed by duplex ultrasound as adjudicated by an independent core laboratory
Ongoing Ranger Clinical Study
Ranger is an investigational device not for sale in the U.S. Source: ClinicalTrials.Gov. June 2014.
Ranger All Comer Registry
P.I. Dr Michael Lichtenberg, Arnsberg (recruiting)
Objective Evaluation of safety and performance of the Ranger Drug Coated Balloon in treatment of subjects with atherosclerotic disease
Study Design Prospective, non-randomized, multicentre trial
Subjects Up to 250 subjects with infra-inguinal atherosclerotic disease eligible for Drug Coated Balloon treatment.
Investigational Centers
10 sites (Germany, Switzerland, and Austria)
Primary Endpoints Major Adverse Events (MAE): composite of device or procedure related mortality and major target limb amputation at 6 months Primary patency at 12 and 24 months, defined as freedom from ≥ 50% restenosis as indicated by duplex ultrasound peak systolic velocity ratio (PSVR) ≥2.4 in the target lesion with no re-intervention
Investigator Sponsored Research – Ranger DCB
Ranger is an investigational device not for sale in the U.S. Source: ClinicalTrials.Gov. June 2014.
Lesion Complexity and Drug-Eluting Technologies
DES?
? ? ? ?
• DCBs seem to have a positive effect in short lesions
• What will new DES add to longer lesions/TASC C and D? Can the downward slope be shifted?
Product Company
Material and Design Sizes Deployment CE
Marked US
Approval
SFA
Zilver PTX
Cook Medical • Nitinol • Polymer-free • Paclitaxel • Zilver Flex stent platform • Pre-mounted on a delivery system
Diameter: 6-8 mm
Length:
20-120 mm
Self-Expandable
Innova DES
Boston Scientific • Nitinol • Biostable polymer matrix • Paclitaxel • Innova stent platform • Tri-axial delivery system
TBD Self-
Expandable No No
BTK
Xience Prime BTK
Abbott Vascular • Cobalt-chromium • Polymer coating • Everolimus
Diameter: 2.5-4mm
Length:
28-38mm
Balloon-Expandable
No
Promus Element Plus BTK
Boston Scientific • Platinum chromium alloy • Fluorinated copolymer • Everolimus • Promus Premier™ platform
Diameter: 2.25-4 mm
Length:
12-38 mm
Balloon-Expandable
Not indicated for BTK in the
US
Stent-Based Drug Elution
Innova and Innova DES are investigational devices not for sale in the U.S.
Innova™ Self-Expanding Stent and the SuperNOVA Trial
SuperNOVA Trial
– 55 sites, 299 patients in the US, Europe and Japan
– Lesions 30 mm to 190 mm
• Broad matrix with diameters 5 - 8 mm and lengths 20 - 200 mm
• Triaxial delivery system
• 6F (2 mm), 0.035” (0.89 mm) compatible
• Commercially available since 2012 in EEA, AMEA, South America, and Canada
Enrollment completion 12M data collection Anticipated approval in the US
2013 2014 2015 2016
CAUTION: Limited by U.S. federal law to investigational use. Not available for use in the U.S. The law restricts these devices to sale by or on the order of a physician. Indications, contraindications, warnings and instructions for use can be found in the product labeling supplied with each device. Information for the use only in countries with applicable health authority product registrations. © 2014 Boston Scientific Corporation or its affiliates. All rights reserved.
MAJESTIC Clinical Study Overview
Name Innova Drug-eluting Stent (Boston Scientific DES SFA Paclitaxel-eluting Self-expanding Stent System)
Objective To determine whether the Boston Scientific nitinol drug-eluting stent shows acceptable performance at 9 months when treating Superficial Femoral (SFA) and/or Proximal Popliteal Artery (PPA) lesions up to 110 mm in length
Study Design Prospective, multicentre, single-arm, open label
Subjects 55 patients with femoropopliteal artery lesions
Investigational Centers
12 sites (Europe, Australia, New Zealand) No center to enroll > 20% (11 subjects) of the total study population
Follow-up Baseline, Procedure, 1 month, 9 months, 1 year, 2 years, 3 years
Primary Endpoint Primary patency of target lesion at 9 months
Innova DES for SFA: MAJESTIC Clinical Study
Innova DES is an investigational device not for sale in the U.S. Clinicaltrials.gov Identifier: NCT01820637
Can Lesion Complexity be Mitigated by Technologies?
Lesion/Vessel Preparation
• 60 patients with SFA stenosis or occlusion treated with DCB1
• At 1 year, greater calcification was associated with: – Lower patency and ABI – Greater late lumen loss and TLR
rate
• DEFINITIVE AR2: directional atherectomy + DCB vs DCB alone
• Adjunctive atherectomy associated with improved procedural and clinical outcomes following DCB treatment of the SFA and/or popliteal artery
Calcium and Drug-coated Balloon Efficacy
ABI, ankle-brachial index; DCB, drug-coated balloon; SFA, superficial femoral artery; TLR, target lesion revascularization. 1. Fanelli F, et al. Cardiovasc Intervent Radiol. 2014 ;37(4):898-907. 2. Zeller, VIVA 2014.
DCB
Atherectomy + DCB
Atherectomy + DCB
(Severe Ca2+)
Technical Success 64.2% 89.6% 84.2%
Bail-out Stent 3.7% 0% 5.3%
Flow-limiting Dissection 19% 2% 0%
Procedural Results
Consensus panel suggests that atherectomy should be considered as part of the SFA treatment algorithm for cases of severe calcification
Rocha-Singh K, Schneider PA, Tepe G, Zeller, T. Refining Strategies for the SFA. Endovascular Today Feb 2014.
Jetstream™ 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 N/A
Differential Cutting N/A
Active Aspiration
Concentric Lumens
Lesion Morphology:
Calcium (large vessel only)
Soft/Fibrotic Plaque
Thrombus (indicated for thrombectomy and
atherectomy)
Atherectomy Devices
Sources: Endovascular Today Buyer’s Guide 2014. JETSTREAM System Brochure, Boston Scientific Website, 2014. Diamondback 360 product website, CSI, 2014. Covidien website, Directional Atheretomy products, 2014. Turbo-Elite Laser Atherectomy Catheter Instructions for Use, May 2014.
• Mechanical removal of thrombus, or • Combination of chemical and mechanical thrombolysis
– Power Pulse Delivery enables infusion of physician-specified fluids directly into the thrombus
• Saline jets create a low pressure zone around the catheter tip that causes
a vacuum effect • Thrombus is drawn into the catheter, where it is fragmented by the jets
and then removed from the body
• Peripheral indications include breaking up and removing thrombus from:
AngioJetTM Thrombectomy Systems
– Infrainguinal peripheral arteries, upper and lower extremity peripheral arteries
– Upper extremity peripheral veins, ileofemoral and lower extremity veins
JETSTREAMTM Atherectomy Systems Caution: Federal (US) law restricts this device to sale by or on the order of a physician. The JETSTREAM System is intended for use in atherectomy of the peripheral vasculature and to break apart and remove thrombus from upper and lower extremity peripheral arteries. It is not intended for use in coronary, carotid, iliac or renal vasculature. See product Information for Use for specific and complete prescribing information. Indications, operating specifications and availability may vary by country. Check with local product representation and country-specific Information For Use for your country. JetStreamTM atherectomy system is manufactured and distributed in EU by Bayer Healthcare. AngioJetTM Thrombectomy Systems for Peripheral Use General Indications/Contraindications AngioJet System peripheral indications include: breaking up and removing thrombus from infra-inguinal peripheral arteries, upper and lower extremity peripheral arteries, upper extremity peripheral veins, ileofemoral, infra-iliac and lower extremity veins, A-V access conduits, and for use with the AngioJet Power Pulse Kit for the control and selective infusion of physician specified fluids, including thrombolytic agents, into the peripheral vascular system. AngioJet System coronary indications include: removing thrombus in the treatment of patients with symptomatic coronary artery or saphenous vein graft lesions prior to balloon angioplasty or stent placement. Do not use in patients: who are contraindicated for intracoronary or endovascular procedures, who cannot tolerate contrast media, and in whom the lesion cannot be accessed with the wire guide. General Warnings and Precautions The System has not been evaluated for treatment of pulmonary embolism in the US and some other countries or for use in the carotid or cerebral vasculature. Some AngioJet devices have not been evaluated for use in coronary vasculature. Operation of the catheter may cause embolization of some thrombus and/or thrombotic particulate debris. Cardiac arrhythmias may occur and cardiac rhythm should be monitored during catheter use and appropriate management employed, if needed. Systemic heparinization is advisable to avoid pericatheterization thrombus and acute rethrombosis. Operation of the System causes transient hemolysis. Large thrombus burdens may result in significant hemoglobinemia which should be monitored. Consider hydration, as appropriate. Before coronary AngioJet treatment, verify the presence of thrombus because routine use of AngioJet in every STEMI patient, without proper selection for thrombus, has been associated with increased mortality risk. Do not use the system in the coronary vasculature without placing a temporary pacing catheter to support the patient through hemodynamically significant arrhythmias which may occur. Potential Adverse Events Potential adverse events (in alphabetical order) which may be associated with use of the system are similar to those associated with other interventional procedures and include but are not limited to the following: abrupt closure of treated vessel, acute myocardial infarction, acute renal failure, arrhythmias (including VF and VT), bleeding from access site, death, dissection, embolization (proximal or distal), emergent CABG, hematoma, hemolysis, hemorrhage requiring transfusion, hypotension/hypertension, infection at access site, myocardial ischemia, pain, pancreatitis, perforation, pseudoaneurysm, reactions to contrast medium, stroke/CVA, thrombosis/occlusion, total occlusion of treated vessel, vascular aneurysm, vascular spasm, vessel wall or valve damage. CAUTION: Federal (USA) Law restricts the device to sale by or on the order of a physician.
Abbreviated Statements
All trademarks are the property of their respective owners.
Take-Home Messages • Recognition of the utility of atherectomy and thrombectomy and their
potential role in enhancing the efficacy of drug-eluting technologies is growing
• In addition to use as primary therapy, atherectomy and thrombectomy facilitate the use of other therapies (eg, atherectomy for calcium removal, promote drug-eluting therapy efficacy)
• Clinical data suggest that treatment with the JetstreamTM Atherectomy System improves stenosis severity, even with severe calcification
• The combination of mechanical thrombectomy and chemical thrombolysis offered by the AngioJetTM Thrombectomy System enables potential benefits such as: thrombus removal in a single procedure, decreased dose and duration of lytic, and decreased bleeding complications
• Proactive venous thrombectomy improves post-thrombotic morbidity
Clearing a Path for the Effective Treatment of Complex Arterial and Venous Disease
An Open Toolbox and Open Questions:
Where are we in Europe with Drug Elution, Atherectomy
and Thrombectomy in 2015? Prof. Dr. Dierk Scheinertert, MD
Universitätsklinikum, Leipzig