Symposium Biotronik High-Tech DRug Eluting Absorbable Metal Stent: dreaming the future! Didier Tchétché. Clinique Pasteur.

Transcription

1 Symposium Biotronik High-Tech 2014 DRug Eluting Absorbable Metal Stent: dreaming the future! Didier Tchétché Clinique Pasteur Toulouse

2 Key characteristics of absorbable scaffold materials Material PLLA 1 Iron 2 Magnesium Alloy 3 Tensile Strength (MPa) ~ Tensile Modulus (GPa) Elongation (%) Total Degradation Time 2-3 Years > 4 years 9-12 months Biocompatibility Absorbable scaffolds Absorption Mechanics 1m 4 28d 28d 180d 2 For coronary scaffolds, tailor-made Magnesium alloys provide the best balance 1 Ratner DB, et al. Biomaterials Science: Introduction to Materials in Medicine, 2 nd Edition. Elsevier Academic Press, /3 Hermanwan H, et al. Developments in metallic biodegradable stents. Acta Biometerialia. 6 (2012): A Cautionary Tale, Ormiston, J., Serruys, P., et al., Circ Cardiovasc Interv 2011;4; , Oct. 2011

3 Vascular restoration therapy: Bioabsorption of magnesium in single steps At the beginning T = 0 T = 0: Post scaffold deployment Drug starts to elute No signs of degradation in coating or metal 3

4 Vascular restoration therapy: Bioabsorption of magnesium in single steps Second phase T = 1 month Drug elutes from the polymer Tissue begins to grow over the strut, start of the healing process Slow hydroxylation of magnesium core into Mg-oxide T = 1 month 4

5 Vascular restoration therapy: Bioabsorption of magnesium in single steps Third phase T = 3 months Drug elution is completed Magnesium is further converted to Mg-oxide and bioabsorption begins Struts are fully covered with tissue T = 3 months 5

6 Vascular restoration therapy: Bioabsorption of magnesium in single steps Fourth phase T = 9 months Magnesium core is fully converted into Mg-oxide. Bioabsorption of Mg-oxide is ongoing Material begins to disassociate and smooth muscle cells infiltrate through the struts T = 9 months 6

7 Vascular restoration therapy: Bioabsorption of magnesium in single steps Fifth phase T = 1 year Most of the scaffold material has been bioabsorbed T = 1 year 7

8 Vascular restoration therapy: Bioabsorption of magnesium in single steps Completed T = 1.5 years All foreign material is gone, only cells are left Vessel has returned to its natural, healed state T = 1.5 years 8

9 From bare AMS to first and second generation DREAMS AMS DREAMS G1 No drug elu8on Paclitaxel + PLGA 165µm 80µm 120µm 90 day animal study 28 day animal study 9 DREAMS Device Overview March 2013 (2010)

10 Six to 24-month clinical follow-up Device success 100% (47 / 47) Procedure success 100% (46 / 46) Clinical results 6-month 1 12-months 1 24-months Cohort 1 & 2 Cohort 1 & 2 Cohort 1&2 TLF 4.3% (2/46) 6.8% (3/44) 6.8% (3/44) Cardiac death 0.0% 0.0% (0/44) 0.0% (0/44) MI 2 0.0% 2.3% (1/44) 2.3% (1/44) Scaffold thrombosis 0.0% 0.0% (0/44) 0.0% (0/44) TLR (clinically driven) 3 4.3% (2/46) 4.5% (2/44) 4.5% (2/44) 1 DREAMS was implanted in the OM and the MI occurred in the LCx. 2 Both pts had angina, 1 pt received an additional DREAMS in the target lesion during the initial procedure because of a flow-limiting bailout. Device Success: successful delivery, deployment, removal of delivery system after release of the scaffold. Safe removal of the device in case of deployment failure. Procedure Success: device success and attainment of a final residual stenosis of < 50%, absence of a MACE during hospital stay to 7 days. 10 M Haude, et al. The Lancet 15 January 2013.

11 6-and 12-month late lumen loss (LLL) Cumulative Frequency (%) month LLL 0.52 ± 0.39 mm 6-month LLL 0.64 ± 0.50 mm 20 PROGRESS-AMS LLL 4 months: 1.08 ±0.49mm 6-month follow-up 12-month follow-up In-Scaffold LLL (mm) 11 M Haude, et al. The Lancet 15 January 2013.

12 BIOSOLVE-I study results Vasomotion results at 12-month (N=18) Mean ±SD 60 Proximal Segment Scaffolded Segment ±9.94% 8.13 ± 10.49% ± 7.44% 8.92 ±9.91% Distal Segment ±13.97% ±16.58% Rela8ve Change in mean lumen diameter % ACH concentra8on Low: 0.36 µg/ml Medium: 3.6 µg/ml High: 18 µg/ml Nitro concentra8on 200 µg/ml - 80 ACH NTG ACH NTG ACH NTG 12

13 Also demonstrates Restoration of Natural Vessel Angulation Change in vessel angulations at 6 months Pre-Procedure Post-Procedure 6-month FUP Pre-Procedure N=47 Post-Procedure Post N=47 6-Month FUP N=36 6 Mo FUP Lesion Angulation ( ) ± ± ± Source: Koolen J. et al; Poster Presentation, TCT 2011

14 OCT measurements for BIOSOLVE Struts fade as evidence of bioabsorption SideB SideB * GWS Ca GWS Ca * * * Post procedure 12Mo FUP

15 From bare AMS to first and second generation DREAMS DRug-Eluting Absorbable Metal Scaffold DREAMS G1 DREAMS G2 Paclitaxel + PLGA Sirolimus + PLLA (BIOlute) 120µm 150µm 90 day animal study 90 day animal study Clinical study started in Oct DREAMS Device Overview March 2013

16 New scaffold design and process allow for improved scaffold expansion DREAMS; crimped (3.0mm nominal) 100% 90% Occurrence probability of of 2nd fractures fracture AMS-3.0 DREAMS S 1st generation Expansion to 3.0mm Occurence Probability 80% 70% 60% 50% 40% 30% 20% 10% AMS-4.0 DREAMS S 2nd generation RFD: (rated fracture diameter*): 4.87mm 0% Initiation of first fractures 1st gen Fracture Diameter [mm] Initiation of first fractures 2nd gen Expansion to 5.4mm One double marker per scaffold end Composite marker with fine Tantalum powder and silicone matrix 16 * RFD= Rated fracture diameter with 99% probability and 95% confidence interval, N=316

17 Potential for side branch access Experimental* post-dilatation of DREAMS G2 shows potential side-branch access D = 1.3mm Kissing balloon inflation: MB 3.0 mm / SB 2.5 mm 5.5mm 17 *Experimental, N=1

18 Coating integrity of DREAMS G2 SEM images of expanded 3.0 mm DREAMS G2 (expansion diameter 3.5 mm) 18 SEM images of expanded 3.0 mm DREAMS G2 (expansion diameter 4.25 mm)

19 Conclusion: what could be the future? Decent degradation time Restoration of vessel integrity and vasomotion Effective eluted drug All comers (bifurcation, tortuosity )? Minimized inflammation Safety and low TLF rate 19

20 THANK YOU 20