INTERVENTIONAL CARDIOLOGY Bioresorbable Stents Update: Similarities. Generation BVS

Transcription

1 INTERVENTIONAL CARDIOLOGY ND ANNUAL INTERNATIONAL SYMPOSIUM Bioresorbable Stents Update: Similarities and Differences in Comparison to First Generation BVS Dariusz Dudek Institute of Cardiology Jagiellonian University, Kraków, Poland Chair, National Cardiac Societies & International Affairs Committee The European Association of Percutaneous Cardiovascular Interventions (EAPCI ESC)

2 Our experience with BVS over 10 years Progressive expansion of angiographic indications from very simple lesion type A (ACC/AHA) to lesions type C (long lesions), different clinical settings FDA approved Absorb in 2016 ST up to 3% but proper technique reduces risk of ST ST up to 3% but proper technique reduces risk of ST up to 70%

3 Development and internal validation of the PSP score the GHOST-EU registry Predilation, correct Scaffold sizing, and Post-dilation with a noncompliant balloon were performed in 95.7%, 50.2%, and 26.2% of the cases and scored 0.63, 1.96 and 1.93 points, respectively, in the PSP-1 model. EuroIntervention Mar 2. pii: EIJ-D

4 Development and internal validation of the PSP score the GHOST-EU registry The PSP score is a simple model for critical assessment of the quality of BVS implantation technique, being an independent predictor of one-year DoCE with poor discrimination and calibration. External validation and prospective studies are mandatory to determine the clinical utility of this score. EuroIntervention Mar 2. pii: EIJ-D

5 Clinical events to 1 year by device and baseline RVD by QCA in the ABSORB III trial. Circulation. 2016;134: DOI: /CIRCULATIONAHA

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7 Vasomotor Response to Nitroglycerine Over 5 Years FU After Everolimus Eluting BVS Implantation Absorb Cohort B (n=101) Group B1 (n=45): with invasive follow up at 6 and 24 months Group B2 (n=56): with control imaging procedures at 12 and 36 months 6 month evaluation excluded (Nitroglicerine test performed after Ach infusion) Dudek D. J Am Coll Cardiol Intv 2017; in press

8 Vasomotor Response to Nitroglycerine Over 5 Years FU After Everolimus Eluting BVS Implantation Dudek D. J Am Coll Cardiol Intv 2017; in press

9 Vasomotor Response to Nitroglycerine Over 5 Years FU After Everolimus Eluting BVS Implantation Response to NTG The response to NTG of the scaffolded segments in comparison with nonscaffolded adjacent segments expressed as changes of normalized mean lumen diameter (LD) percent change over time. Plot with standard errors. Dudek D. J Am Coll Cardiol Intv 2017; in press

10 Dudek D. J Am Coll Cardiol Intv 2017; in press

11 Vasomotor Response to Nitroglycerine Over 5 Years FU After Everolimus Eluting BVS Implantation WHAT IS KNOWN? The appearance of vasomotility up to 2 years after ABSORB implantation was previously shown. WHAT IS NEW? We have not found improvement in response to NTG using mean lumen diameter change by QCA. Only the maximal LD change increased significantly. This suggests a trend toward vasomotor recovery in 5-year follow-up, which is consistent with the progressive degradation and bioresorption of the scaffold; however, the degree of response to NTG remained lower than in adjacent segments. WHAT IS NEXT? Different stimulation agents and/or different methodology should be applied in further studies to verify these findings. Dudek D. J Am Coll Cardiol Intv 2017; in press

12 COMPARE ABSORB TRIAL: STUDY SCHEDULE

13 Bioresorbable vascular scaffold (BVS) commercially available and and those under clinical development. Poly-L-lactic acid platform Tyrosine polycarbonate alloy Magnesium framework Panminerva Medica 2016 June;58(2):130-42

14 WORKHORSE DESolve Bioresorbable Scaffold Portfolio 150µm strut thickness 120µm strut thickness 120µm contoured strut INDICATION SPECIFIC Pharmaceutical: Novolimus 5 µg/mm of scaffold length PRAVA Shape Memory Designed for AMI DESolve is CE Mark approved; not available for sale DESolve CX and DESolve NXT are not available for sale. AMITY is not available for sale. Clinical trial is required for AMI indication. PRAVA is not available for sale and developed by Akesys Medical. Designed for SFA

15 DESolve Key Features One year degradation allowing early vascular restoration Fracture resistance Unique self correction Early lumen and scaffold enlargement at 6 months Sustained safety and efficacy out to 4 years PostProcedure 6-Month Follow-up 36-Month Follow-up

16 DESolve Cx Case Study I M 24/05/1935 I XA Baseline XA XA 15/09/ :20:15 Calibrated : mm/pixel Courtesy of Dr. Verheye, ZNA Antwerpen NOT CALIBRATED Calibrated : mm/pixel

17 DESolve Cx Clinical Trial 6 Month Clinical Outcomes Hierarchical Events 0 to 180 days, n 30 days (N=50) 6 months (N=25) 0 0 Cardiac Death 0 0 Target Vessel MI 0 0 Q-wave MI 0 0 Non-Q- wave MI 0 0 Clinically Indicated-TLR 0 0 Definite/probable Stent Thrombosis 0 0 Major Adverse Cardiac Events

18 Next Generation BRS 120µm contoured struts designed for improved acute performance Enhanced force transmission to minimize snow shoe effect Augment scaffold embedding into the vessel Optimize lesion expansion

19 TRANSFORM Balloon Technology Balloon central segment expands to 0.25mm larger than the end segments at nominal pressure 3mm length segments on proximal and distal ends expand to nominal diameter Smooth dome-shaped transition Single balloon material 3mm 3mm For a 3.0mm diameter balloon: Mid segment will be 3.25mm at nominal

20 AMITY Designed to address the unmet clinical needs of STEMI and CTO indication Overcome stent malapposition due to Underdeployed scaffold thrombus resolution in STEMI Address stent under-sizing due to vessel spasm Compensate for stent under-sizing due to vessel normalization post CTO revascularization BRS has the potential for plaque sealing/stabilization by restoring endothelial function and inducing positive remodeling AMI/CTO procedures are 25-30% of the PCIs. AMITY is not available for sale. AMITY requires a clinical trial for AMI indication. BRS

21 First PRAVA Implant Pre-procedure Final

22 REVA Clinical Program

23 FANTOM Bioresorbable Scaffold (Reva Medical) Sirolimus-ElutingBRS Iodinated Desaminotyrosine Polycarbonate Key Features DES-like scaffold visibility under x-ray Single-step continuous inflation Good expansion range Good radial strength at 125 µm thickness Vasomotion restoration ~1 year (preclinical) No special storage or handling requirements Visibility Deliverability VesselPatency

24 FANTOM BRS: Conclusions Fantom offers new and clinically important features Radiopacity Deliverability Single-step inflation No special handling Initial clinical data demonstrates: Good acute performance Enhanced device deliverability Minimal residual stenosis and acute recoil (3%) Sustained performance and safety through 6 months Low MACE rate (2.1%) and scaffold thrombosis (0.4%) Low late lumen loss (0.25mm)

25 Amorphous poly-l-lactic acid based BRS (Amaranth BRS) In vitro biomechanical testing was performed under static and cyclic conditions. A total of 99 devices (65 Amaranth BRS versus 34 Absorb BVS) were implanted in 99 coronary arteries of 37 swine. Circ Cardiovasc Interv. 2016;9:e004253

26 Biotronik Magnesium Scaffold Magnesium Absorption Process 1 month acute Mg absorption 3-12 months Mg absorption 12 months Mg absorption Lancet Jan 2;387(10013):31-9. doi: /S (15)00447-X.

27 Magmaris shows a rapid endothelial coverage Endothelial coverage at 28 days Preclinical test In a rabbit study, endothelialisation was evalutated with SEM* 28 days after implantation. Higher endothelialisation is associated with a lower thrombosis risk. Rapid endothelial coverage: Magmaris shows 15 % better endothel-ialization compared to the leading polymeric scaffold, especially above struts Leading polymeric scaffold Magmaris 27 CE mark pending 17th New Frontiers in Interventional Cardiology *SEM=Scanning Electron Microscope BIOTRONIK data on file Kraków, Dec

28 Background Evolution of the BIOTRONIK Magnesium Scaffold Device generation AMS DREAMS 1G DREAMS 2G Ø 3.0 & 3.5 Length: 15, 20 Ø3.25 & 3.5 Length: 15 Ø 2.5, 3.0 & 3.5 Length: 15, 20, 25 Mg alloy Refined Mg alloy Refined Mg alloy 165/80 μm 120/130 μm 120/120 μm (Ø 2.5) 150/150 μm (Ø 3.0 & 3.5 ) Markers none none Ta-composite Coating - drug none PLGA/PTX PLLA/SIR Crossing profile in mm Drug elution kinetics n.a. like Taxus like Orsiro Absorption period in month (Mg) 12 (Mg) In-segment Late Lumen Loss (mm) 0.83± ±0.48? In-scaffold Late Lumen Loss (mm) 1.08± ±0.50? TLF* (%) ? Definite or Probable Scaffold Thrombosis (%) ? Sizes (mm) Results Kinetic Design Backbone Strut thickness/width *Composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization and CABG Lancet Jan 2;387(10013):31-9. doi: /S (15)00447-X.

29 Vasomotion Results at 6-month (N=25) Mean Lumen Diameter Proximal (mm±sd) 2.68± ±0.56 Ach = Acetylcholine Nitro = Nitroglycerine 2.76±0.46 Mean Lumen Diameter Scaffold (mm±sd) 80% (20/25) demonstrate 2.60± ± ±0.33 3% vasomotion after Ach or Nitro Mean Lumen Diameter Distal (mm±sd) 2.39± ± ±0.40 Lancet Jan 2;387(10013):31-9. doi: /S (15)00447-X.

30 Comparison of in-segment LLL in PROGRESS, BIOSOLVE-I and BIOSOLVE-II Cumulative Frequency (%) 100 PROGRESS (4-month) BIOSOLVE-I (6-month) BIOSOLVE-II (6-month) ± ± ± % -37% PROGRESS vs BIOSOLVE-II: p < BIOSOLVE-I vs BIOSOLVE-II: p= Late Lumen Loss (mm) Lancet Jan 2;387(10013):31-9. doi: /S (15)00447-X.

31 Magmaris implantation NFIC 2016 Institute of Cardiology, Jagiellonian University Krakow, Poland

32 PCI of RCA Magmaris 3.5x26mm introduction Magmaris 3.5x26mm implantation

33 PCI of RCA Post Magmaris Second Magmaris introduction 3.5x15mm

34 Final angiography of RCA Final LAO post postdil with 4.0x20 18 atm Final LAO

35 Present and future of BRS in cardiology as 4th revolution of POBA/PCI Progressive expansion of angiographic indications: from very simple lesion type A (ACC/AHA) to lesions type C (long lesions), different clinical settings FDA approved Absorb in 2016 Second generation Absorb in near future Desolve increasing number of data Magnesium stent CE marked in 2016 starting Fantom - ongoing clinical program Mirage /Amaranth- new platforms and designs

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37 Amorphous poly-l-lactic acid based BRS (Amaranth BRS) There were no differences in minimum lumen diameter,percent diameter stenosis, and late lumen loss for both Amaranth BRS and Absorb BVS at any of the time points. Circ Cardiovasc Interv. 2016;9:e004253

38 OCT variables at 1-, 3-, and 6-mo follow-up Amaranth BRS vs. Absorb BVS Circ Cardiovasc Interv. 2016;9:e004253

39 MIRAGE Microfiber sirolimus-eluting bioresorbable scaffolg (MMSES)

40 MIRAGE specifications

41 Conclusion DREAMS 2G in BIOSOLVE-II demonstrates significantly improved in-segment LLL (0.27±0.37mm) compared to it`s precursor devices tested in the PROGRESS (0.83±0.37mm) and the BIOSOLVE-I study (0.52±0.48mm) Vasomotion of the scaffolded vessel segment was demonstrated at 6 months IVUS results in a subgroup of 30 subjects demonstrate a preservation of the scaffold area with a low neo-intimal area at 6-month No intra-luminal masses were observed by OCT at any time in a subgroup of 25 subjects DREAMS 2G in BIOSOLVE-II demonstrates a low TLF (3.3%) and TLR (1.7%) rate at 6-month, which is comparable to other absorbable scaffolds and permanent drug eluting stents No definite or probable scaffold thrombosis was observed with DREAMS 2G tested in BIOSOLVE-II or any of it`s precursor devices tested in PROGRESS and BIOSOLVE-I in a total of 232 subjects Lancet Jan 2;387(10013):31-9. doi: /S (15)00447-X.

42 Magmaris implantation NFIC 2016 Institute of Cardiology, Jagiellonian University Krakow, Poland

43 Baseline angiography of RCA

44 PCI of RCA Difficulties in ballon NC 3.5x15 advancement Small 2.5x15mm inflation

45 PCI of RCA Cutting 3.5x15mm Flextome Post NC 3.5x15mm

46 PCI of RCA Magmaris 3.5x26mm introduction Magmaris 3.5x26mm implantation

47 PCI of RCA Post Magmaris Second Magmaris introduction 3.5x15mm

48 Final angiography of RCA Final LAO post postdil with 4.0x20 18 atm Final LAO

49 Present and future of BRS in cardiology as 4th revolution of POBA/PCI Progressive expansion of angiographic indications: from very simple lesion type A (ACC/AHA) to lesions type C (long lesions), different clinical settings FDA approved Absorb in 2016 Second generation Absorb in near future Desolve increasing number of data Magnesium stent CE marked in 2016 starting Fantom - ongoing clinical program Mirage /Amaranth- new platforms and designs