Current Status of BioresorbableScaffolds: Moving Forward or Backwards?

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1 Evolving Science of Stents Current Status of BioresorbableScaffolds: Moving Forward or Backwards? Christian W. Hamm Kerckhoff Heart and Thorax Center Bad Nauheim and Medical Clinic I, University of Giessen, Germany

2 Affiliation/Financial Relationship Conflict of Interest Disclosure Christian W. Hamm Company Honoraria for lectures: Abbott, AstraZeneca,Bayer, Boehringer Ingelheim, CVRx, BRAHMS, Daiichi Sankyo, Medtronic, Lilly, MSD, SanofiAventis, Pfizer, Roche, Servier, The Med. Comp., Boston Scientific, Gilead Honoraria for advisory board activities: Aspen, AstraZeneca, Bayer, BRAHMS, CVRx, Boehringer Ingelheim, Medtronic, SHS, Zoll Participation in clinical trials: Financial shares and options: no AstraZeneca, Boston Scientific,

3 Advances in Interventional Cardiology Mechanisms of Restenosis recoil Restenosis rate 40% 20% Stabilisation Neointima Formation 5% Antiproliferative Drugs PTCA 1978 BMS 1992 DES 2002?

4 ENDEAVOR IV: 1 st versus 2 nd Generation DES Cumulative Incidence of Cardiac Death/MI to 5 Years Cumulative Incidence of Cardiac Death/MI (%) 10% 8% 6% 4% 2% Endeavor ZES Taxus PES Log Rank P = % (66) 6.4% (46) 0% Time After Initial Procedure (Years)

5 Shortcomings of DES (Late) Stent-thrombosis Metal Jacket : option CABG? Stiffness Loss of Vasomotion Psychology: foreign body

6 Why bioresorbable? - Late Stent Thrombosis The Risk Never Completely Disappears (12 JahreafterDES-Implantation) Stent (DES) J Invasive Cardiol 2008;20:E

7 Why bioresorbable?? Future option: CABG Khouzam et al. JACC 2010;56:1605

8 Non-invasive CT Imgaging Why bioresorbable? DES

9 BioresorbableScaffolds Name ABSORB BVS Technique Poly Lactid Acid(PLLA) + Everolimus REVA: Resolve Tyrosinepolycarbonate + Paclitaxel BTI Polymerstruts with Salicylic acid + Sirolimus ARTS DESolve Xinsorb PLLA PLLA + Novolimus PLLA + Sirolimus

10 Scaffold Strut Poly Lactic Acid Scaffolds Lactic Acid DIFFUSION Lactic acid is readily converted to lactate, a common fuel source for multiple metabolic pathways 1 Lactic Acid Lactate Lactate Intracellular Mitochondrion H 2 O CO 2 Krebs Cycle 1 Philp A., et al., J. Exp. Biol. 2005; 208: 4561

11 ABSORB Completely Resorbs in About 2 Years Through a Natural Process No evidence of inflammation around the strut regions Between the 1- and 2-year time points, polymer is replaced by extracellular matrix Between the 2- and 3- year time points, matrix is replaced by natural smooth muscle cells 1 month 3 months 6 months 1 year 2 years 3 years Revascularization Restoration Resorption Porcine Coronary Artery Model On file at Abbott Vascular.

12 Adaptive Remodelling? Lumen enlargement(data from ABSORB B1 und B2)

13 STEMI

14 STEMI

15 STEMI Follow-up after 4 Weeks

16 How solid are the data? Observational Randomized Registry

17 Registries with ABSORB BVS Endpoints after 30-days FU GABI-R n = 1536 GHOST-EU n = Events in % TVF (CV-death, TV-MI, TVR) All-cause Mortality (CV- Death, Noncardiac death) CV-Death non CV-Death MI TVR ARC ST definite/probable MACE (CV-Death, Any MI, TVR) 17

18 Target Lesion Failure 20% Absorb BVS (n=1322) Xience CoCr-EES (n=686) TLF (%) 15% 10% 5% Diff [95% CI] = 1.7% [-0.5% to 3.9%] P superiority = % 6.0% 0% No. at Risk: Absorb 1322 Xience Months Post Index Procedure Ellis et al. New Eng. J. Med 2015

19 DESolve (Elexir) KERCKHOFF KLI NI K

20 DESolve Post-marketclinicalFU (PMCF) % N= 102 patients 30d FU 6 Mo FU MACE (Cardiac death, Any MI, Target lesion revascularization) Cardiac Death TV-MI CD-TLR Definite/Probable ST Hierarchical events Nefet al. TCT 2015

21 Magnesium-based Scaffolds acute 3 months 6 months 9 months Scaffolding Drug release Mg + 2H 2 O Mg(OH) 2 + H 2 Soft amorphous Cax(PO 4 )y Mg Mg Drug carrier elutes drug Slow hydroxylation of Mg Mg alloy Mg degradation product Polymer Mg hydroxylation is complete Drug release complete Bioabsorption of polymer ongoing Bioabsorption of Mg(OH) 2 is complete Drug carrier layer bioabsorption ongoing Structural disintegration begins

22 OCT measurements for BIOSOLVE Struts fade as evidence of bioabsorption SideB SideB GWS * Ca GWS Ca * * * Post procedure 12Mo FUP Garcia-Garcia HM et al..

23 2 nd -generation drug-eluting absorbable metal scaffold BIOSOLVE-II Study: 6 month outcome M.Haude, et al. The Lancet 2015

24 Hazards of Bioresorbable Scaffolds Stent thrombosis Side branch occlusions Excavations/ Evaginations

25 Stent Thrombosis Windeckeret al, J Am CollCardiol, 2015

26 Device Thrombosis to 1 Year Absorb (N=1322) Xience (N=686) p-value Device Thrombosis (def*/prob) 1.54% 0.74% Early (0 to 30 days) 1.06% 0.73% Late (> 30 to 1 year) 0.46% 0.00% Definite* (1 year) 1.38% 0.74% Probable (1 year ) 0.15% 0.00% 0.55 Ellis et al. New Eng. J. Med 2015

27 Side branch occlusions? Incidence of post-procedural Sidebranch occlusion

28 OCT 6 months 6 months

29 Conclusions Bioresorbable Scaffolds2015 Acute results satisfactory Safety still of concern (early/ late ST) RCT data still poor

30 Evolving Science of Stents The Gardner Hype Cycle DES Attrib. Gardner Group Inc.

31 Thank you! KERCKHOFF KLINIK

32 Evolving Science of Stents The Gardner Hype Cycle of Innovations DES Attrib. Gardner Group Inc.

33 ABSORB (Abbott Vascular) Bioresorbable Scaffold Bioresorbable Coating Everolimus XIENCE V Delivery System

34 Endpoints after 30-days FU GABI-R GHOST-EU n = 1536 n = Events in % Stent Thrombosis TVF (CV-death, TV-MI, TVR) All-cause Mortality (CV- Death, Noncardiac death) CV-Death non CV-Death MI TVR ARC ST definite/probable MACE (CV-Death, Any MI, TVR) 34