Clearing a Path for the Effective Treatment of Complex Arterial and Venous Disease

Transcription

1 Clearing a Path for the Effective Treatment of Complex Arterial and Venous Disease 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?

2 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

3 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.

4 Lesion Complexity Affects Outcomes Longer lesions are associated with poorer PTA and BMS outcomes, even in predominately TASC A and B classifications TASC A and B Lesions Bosiers M, LINC 2014.

5 Can Lesion Complexity be Mitigated by Technologies? Drug Elution

6 Lesion Complexity and Drug-Eluting Technologies DCBs seem to have a positive effect in short lesions TASC A and B Lesions Bosiers M, LINC 2014.

7 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 lesions 1-7 Primarily TASC A/B, lesion length <10 cm Less calcification RCT FemPac 1 THUNDER 2 PACIFIER 3 LEVANT I 4 LEVANT II 5 SFA 6 IN.PACT N (DCB arm) Mean lesion length (cm) 4.0 (median) Calcified 53% 50% 64% severe excluded Total occlusion Registry Italian Registry 7 59% 8% 50% moderate 17% severe 13% 27% 23% 41% 21% 26% 30% 1. Werk M, et al. Circulation. 2008;118: Tepe G, et al. N Engl J Med. 2008;358: Werk M, et al. Circ Cardiovasc Interv. 2012;5: Scheinert D, et al. JACC Cardiovasc Interv. 2014;7: Rosenfield K. TCT Tepe G, et al. Circulation. 2014; Epub ahead of print. 7. Micari A, et al. JACC Cardiovasc Interv. 2013;6:

8 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 lesions 1-7 Primarily TASC A/B, lesion length <10 cm Less calcification DCB effect in lesions 10 cm investigated in one retrospective study 8 12-month TLR rate within the range reported in shorter-lesion trials 30% 20% 10% 12-month TLR Rate <10 cm 10 cm 0% FemPac LEVANT II PACIFIER THUNDER LEVANT I IN.PACT SFA Zeller et al (2014) Mean lesion length 1. Werk M, et al. Circulation. 2008;118: Tepe G, et al. N Engl J Med. 2008;358: Werk M, et al. Circ Cardiovasc Interv. 2012;5: Scheinert D, et al. JACC Cardiovasc Interv. 2014;7: Rosenfield K. TCT Tepe G, et al. Circulation. 2014; Epub ahead of print. 7. Micari A, et al. JACC Cardiovasc Interv. 2013;6: Zeller T, et al. J Endovasc Ther. 2014;21:

9 IN.PACT SFA Trial 12-Month Primary Patency (Clinically-driven TLR, PSVR >2.4) Clinically-driven TLR ABI decrease >0.15 or 20%, or symptoms 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, Schneider P. TCT Tepe G, et al. Circulation. 2014; Epub ahead of print.

10 Market Revenue ($m) DCB for PAD: A look ahead Global* DCB Market for treating PAD in the lower extremity ($m), Year Infrapopliteal artery Femoropopliteal artery 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) GlobalData. MediPoint: Drug-Eluting Balloons Global Analysis and Market Forecasts. Sep 2013 *US, France, Germany, Italy, Spain, UK, Japan, China, India, Brazil

11 Peripheral Drug-Coated Balloons Company Device Drug Coating Dose Density (μg/mm 2 ) 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.

12 Ranger Drug-Coated Balloon 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 guidewires Size matrix: SFA: 4-8 mm; mm BTK: 2-4 mm; up to 150 mm Ranger is an investigational device not for sale in the U.S.

13 Ongoing Ranger Clinical Study Clinical Study Overview: Ranger Name Objective Ranger DCB 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 Subjects Investigational Centers Primary Endpoint Prospective, randomized, multicenter, controlled trial (2:1 Ranger DCB vs. uncoated balloon) 105 patients with femoropopliteal artery lesions 11 sites (Germany, France, and Austria) Primary patency at 6 months post-procedure assessed by duplex ultrasound as adjudicated by an independent core laboratory Ranger is an investigational device not for sale in the U.S. Source: ClinicalTrials.Gov. June 2014.

14 Ranger All Comer Registry P.I. Objective Investigator Sponsored Research Ranger DCB Dr Michael Lichtenberg, Arnsberg (recruiting) Evaluation of safety and performance of the Ranger Drug Coated Balloon in treatment of subjects with atherosclerotic disease Study Design Subjects Investigational Centers Primary Endpoints Prospective, non-randomized, multicentre trial Up to 250 subjects with infra-inguinal atherosclerotic disease eligible for Drug Coated Balloon treatment. 10 sites (Germany, Switzerland, and Austria) 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 Ranger is an investigational device not for sale in the U.S. Source: ClinicalTrials.Gov. June 2014.

15 Lesion Complexity and Drug-Eluting Technologies 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????? DES?

16 Stent-Based Drug Elution Product Company Material and Design Sizes Deployment CE Marked US Approval Zilver PTX Cook Medical Nitinol Polymer-free Paclitaxel Zilver Flex stent platform Pre-mounted on a delivery system Diameter: 6-8 mm Length: mm Self- Expandable SFA Innova DES Boston Scientific Nitinol Biostable polymer matrix Paclitaxel Innova stent platform Tri-axial delivery system TBD Self- Expandable No No Xience Prime BTK Abbott Vascular Cobalt-chromium Polymer coating Everolimus Diameter: 2.5-4mm Length: 28-38mm Balloon- Expandable No BTK Promus Element Plus BTK Boston Scientific Platinum chromium alloy Fluorinated copolymer Everolimus Promus Premier platform Diameter: mm Length: mm Balloon- Expandable Not indicated for BTK in the US Innova and Innova DES are investigational devices not for sale in the U.S.

17 Innova Self-Expanding Stent and the SuperNOVA Trial Broad matrix with diameters 5-8 mm and lengths mm Triaxial delivery system 6F (2 mm), (0.89 mm) compatible Commercially available since 2012 in EEA, AMEA, South America, and Canada SuperNOVA Trial 55 sites, 299 patients in the US, Europe and Japan Lesions 30 mm to 190 mm Enrollment completion 12M data collection Anticipated approval in the US 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 Boston Scientific Corporation or its affiliates. All rights reserved.

18 Innova DES for SFA: MAJESTIC Clinical Study MAJESTIC Clinical Study Overview Name Objective Innova Drug-eluting Stent (Boston Scientific DES SFA Paclitaxel-eluting Self-expanding Stent System) 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 Subjects Investigational Centers Follow-up Primary Endpoint Prospective, multicentre, single-arm, open label 55 patients with femoropopliteal artery lesions 12 sites (Europe, Australia, New Zealand) No center to enroll > 20% (11 subjects) of the total study population Baseline, Procedure, 1 month, 9 months, 1 year, 2 years, 3 years Primary patency of target lesion at 9 months Innova DES is an investigational device not for sale in the U.S. Clinicaltrials.gov Identifier: NCT

19 Can Lesion Complexity be Mitigated by Technologies? Lesion/Vessel Preparation

20 Calcium and Drug-coated Balloon Efficacy 60 patients with SFA stenosis or occlusion treated with DCB 1 At 1 year, greater calcification was associated with: Lower patency and ABI Greater late lumen loss and TLR rate DEFINITIVE AR 2 : 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 Procedural Results DCB Atherectomy + DCB Atherectomy + DCB (Severe Ca 2+ ) Technical Success 64.2% 89.6% 84.2% Bail-out Stent 3.7% 0% 5.3% Flow-limiting Dissection 19% 2% 0% ABI, ankle-brachial index; DCB, drug-coated balloon; SFA, superficial femoral artery; TLR, target lesion revascularization. 1. Fanelli F, et al. Cardiovasc Intervent Radiol ;37(4): Zeller, VIVA 2014.

21 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.

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

23 AngioJet TM Thrombectomy Systems 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: Infrainguinal peripheral arteries, upper and lower extremity peripheral arteries Upper extremity peripheral veins, ileofemoral and lower extremity veins

24 Abbreviated Statements JETSTREAM TM 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. JetStream TM atherectomy system is manufactured and distributed in EU by Bayer Healthcare. AngioJet TM 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. All trademarks are the property of their respective owners.

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26 Clearing a Path for the Effective Treatment of Complex Arterial and Venous Disease 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 Jetstream TM Atherectomy System improves stenosis severity, even with severe calcification The combination of mechanical thrombectomy and chemical thrombolysis offered by the AngioJet TM 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

27 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