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James Hermiller, MD, FACC, FSCAI The St Vincent Medical Group The St Vincent Heart Center of Indiana Indianapolis, IN Drug-Eluting Stents 2013: Current.

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Presentation on theme: "James Hermiller, MD, FACC, FSCAI The St Vincent Medical Group The St Vincent Heart Center of Indiana Indianapolis, IN Drug-Eluting Stents 2013: Current."— Presentation transcript:

1 James Hermiller, MD, FACC, FSCAI The St Vincent Medical Group The St Vincent Heart Center of Indiana Indianapolis, IN Drug-Eluting Stents 2013: Current Data and Future Advances Hilton La Jolla Torrey Pines La Jolla, California - Oct 3 rd, 2013 BLBL 2Y2Y

2 Disclosures Consulting Fees/Honoraria Speaker Bureau Abbott, BSC, Medtronic and St Jude Medicines Company Affiliation/Financial Relationship Company

3 Outline Introduction Current Data Advances to Date Future Directions Metallic DES Bioabsorbable Polymer Metallic DES with No Polymer Completetly Bioabsorbable DES Conclusions and Summary Introduction Current Data Advances to Date Future Directions Metallic DES Bioabsorbable Polymer Metallic DES with No Polymer Completetly Bioabsorbable DES Conclusions and Summary

4 Introduction: DES Talks

5 First Generation DES PES Polyolefin derivative Paclitaxel Express 2 DrugPolymerStent SES PEVA + PBMA blend Sirolimus BX Velocity

6 1 st Gen Drug-Eluting Stents The good, the bad, and the ugly! 1 st Gen Drug-Eluting Stents The good, the bad, and the ugly! 7 years 40 mos BMS DES Incompleteapposition Late stent thrombosis Abn Vasomotion *P<0.001 vs. control Sirolimus Control * * Delayed Healing! Angioscopy BMS DES Late loss = 0 Eos Giant cells IVUS Inflammation

7 Second Generation DES ZES BioLinx copolymer ZotarolimusIntegrity DrugPolymer EES VDF + HFP copolymer Everolimus Vision Stent Omega

8 StentEES - PROMUS ZES - Resolute EES - Xience Expedition Underlying Stent PtCr – Element (Omega) CoCr – Integrity CoCr – Modified Vision Strut Thickness ”0.0036”0.0032” Strut Pattern Lengths (mm) (Diameters 2.25 to 4.0 mm) 8,12,16,20,24,2 8, 32, and 38 mm (38 for >2.75 mm diameter) 9,12,15,18,22,26, 30, 34 and 38 mm (34 and 38 for >3.0 mm diameter) 8,12,15,18,23,28, 33, and 38 mm (33 and 38 mm for >2.5 mm diameter) Current Stent Attributes

9 Stent EES – PROMUS ELEMENT ZES - ResoluteEES – Expedition Max Expansion (mm) 2.25 to & 2.75 to & 3.5 to to – 2.75 to – 4.0 to & 2.5 to &3.0 to & 4.0 to 4.75 Sidebranch Cell Size (Max Expansion) 2.25 to & 2.75 to & 3.5 to to to 4.0 to 9.24 mm 6 Cresst to 3.0 to 3.5mm 9 Crest – 3.5 & 4.0 to 4.2 mm Polymer DrugFluorinated Copolymer - EES Biolinx Polymer ZES Fluorinated Copolymer - EES In Stent Late Loss<0.2mm Current Stent Attributes

10 Cumulative incidence (%) EES SES PES No. at risk Months after index PCI Sirolimus Stent 2.9% Everolimus Stent 1.4% Paclitaxel Stent 4.4% ARC Definite 4 Years EES vs. SES Hazard Ratio* = 0.41, 95% CI 0.27–0.62, P< EES vs. PES Hazard Ratio* = 0.33, 95% CI , P < Räber L, ESC 2011 Bern-Rotterdam Cohort Study

11 Cumulative incidence (%) Months after index PCI EES vs. SES HR* = 0.33, 95% CI 0.15 – 0.72, P=0.006 EES vs. PES HR* = 0.24, 95% CI , P < Very Late ST (1-4 yrs) Sirolimus Stent 1.6% Everolimus Stent 0.6% Paclitaxel Stent 2.4% * from Cox proportional hazards model Bern-Rotterdam Cohort Study Räber L, ESC 2011

12 SPIRIT II, III, IV and COMPARE trials Pooled database analysis (n=6,789) Ischemic TLR P<0.001 HR: 0.60 [0.48, 0.75] EES (n=4,247) PES (n=2,542) Number at risk XIENCE TAXUS 6.6% 6.6% Ischemic TLR (%) 0 10 Time in Months % 4.1% 5 4.7% 2.3% ∆=2.4% ∆=2.5% Kereiakes DJ et al. EuroIntervention 2011:7:74-83

13 SPIRIT II, III, IV and COMPARE trials Pooled database analysis (n=6,789) Stent thrombosis (ARC definite/probable) Number at risk XIENCE TAXUS 2.3% 2.3% Stent thrombosis ARC def or prob (%) Time in Months % 0.7% p<0.001 HR: 0.30 [0.19, 0.47] EES (n=4,247) PES (n=2,542) Kereiakes DJ et al. EuroIntervention 2011:7:74-83

14 Time after Initial Procedure (Months) Cumulative Incidence of Events 11.2% 10.7% 0% % 5% 15% 10% Log rank P = 0.73 Resolute ZES (N = 1140) Xience V EES (N = 1152) Silber S, et al. Lancet. 2011;377: RESOLUTE All Comers Target Lesion Failure to 2 Years (Cardiac Death, TV-MI, CD-TLR)

15 TWENTE (n=1,387) Target Vessel Failure at 2-Year Follow-up Von Birgelen C. TCT TVF (%) Follow-up (days) Xience V (n=692) Resolute (n=695) P = % 10.9%

16 Presented by Ian T Meredith MBBS, PhD at ACC 2013 EES Pt-Cr vs EES Co-Cr 3-Year Clinical Results Incidence Rate (%) p = 0.81 p = 0.21 p= 0.75 p = 0.40 Xienca CoCr EESPromus PtCr EES p = 0.27 p= 0.30

17 Longitudinal stent deformation: Angiographic patterns Longitudinal stent compression: Manifests itself as a dark band in the region of compression (also called stent “accordion”, “concertina”, “wrinkling”, etc.)Longitudinal stent compression: Manifests itself as a dark band in the region of compression (also called stent “accordion”, “concertina”, “wrinkling”, etc.) Longitudinal stent elongation: Appears like a fracture in the stent (pseudo-fracture)Longitudinal stent elongation: Appears like a fracture in the stent (pseudo-fracture) Longitudinal elongation with pseudo-fracture Longitudinal compression

18 Retrospective analysis of longitudinal stent deformation in the “real world”: Study 2,936 Promus Element stents implanted in 2,839 lesions in 1,295 pts at a single center over 22 months LSD occurred in: 1.4% (n=20) of pts (95%CI 0.9%-2.2%) 0.7% of lesions (95%CI 0.4%-1.1%) 0.7% of Promus Element stents (95%CI 0.4%-1.1%) Multivariable predictors of LSD: # and length of stents, ostial and bifurcation lesions 30 Day MACE in pts with LSD = 5.0% (1 NQMI) Leibundgut G et al. CCI 2012: doi: /ccd.24472

19 Promus PREMIER Everolimus-Eluting Stent Additional connectors on proximal end Provide increased axial strength 2 connectors throughout body Customized Platinum Chromium (PtCr) Stent Architecture Enhanced Stent Delivery System Shorter tip to improve flexibility PTFE Coating on hypotube to reduce friction

20 Sarno et al, Eur Heart J 2012 SCAAR Registry (94,384 pts) Adjusted Risks of Adverse Events at 2 yrs BMS “Old DES” “New DES” RestenosisDefinite ST Restenosis Definite Stent Thrombosis Old DES = SES, PES, ZES-Endeavor; New DES = EES, ZS-Resolute

21 Bangalore S et al. Circulation 2012:On-line Network Meta-analysis Endpoints: Death, MI, ST, TVR early (<1 yr) and late 77 RCTs, 57,138 pts, 117,762 pt-yrs of FU Evidence network Paclitaxel-ElutingSirolimus-Eluting BMS Zotarolimus-ElutingEverolimus-Eluting Zotarolimus-Eluting- Resolute

22 Bangalore S et al. Circulation 2012:On-line Network Meta-analysis: 1-year Definite ST OR [95% CrI] 0.10 OR (95% Crl) Favors Control Favors Treatment ControlTreatment BMS (Ref) Sirolimus Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 0.75 (0.45, 1.20) 0.81 (0.51, 1.48) 1.34 (0.63, 3.21) 0.41 (0.41, 12.53) 0.27 (0.14, 0.55) Sirolimus (Ref) Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 1.10 (0.66, 1.91) 1.79 (0.91, 4.04) 2.73 (0.60, 16.87) 0.36 (0.20, 0.70) Paclitaxel (Ref) Zotarolimus-E Zotarolimus-R Everolimus 1.70 (0.76, 3.60) 2.52 (0.51, 14.79) 0.34 (0.18, 0.61) Everolimus (Ref) Zotarolimus-E Zotarolimus-R 5.16 (2.09, 12.31) 7.44 (1.88, 39.43) Zotarolimus-R1.55 (0.29, 9.83) Zotarolimus-E (Ref) 77 RCTs, 57,138 pts, 117,762 pt-yrs of FU

23 Bangalore S et al. Circulation 2012:On-line Network Meta-analysis: 1-year MI 77 RCTs, 57,138 pts, 117,762 pt-yrs of FU OR [95% CrI] 0.10 OR (95% Crl) ControlTreatment Favors Control Favors Treatment BMS (Ref) Sirolimus Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 0.67 (0.53, 0.84) 0.87 (0.71, 1.04) 0.66 (0.49, 0.84) 0.55 (0.38, 0.82) 0.55 (0.41, 0.73) Sirolimus (Ref) Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 1.28 (1.08, 1.55) 0.97 (0.73, 1.25) 0.81 (0.58, 1.17) 0.82 (0.65, 1.03) Paclitaxel (Ref) Zotarolimus-E Zotarolimus-R Everolimus 0.75 (0.57, 0.96) 0.63 (0.46, 0.91) 0.63 (0.52, 0.81) Everolimus (Ref) Zotarolimus-E Zotarolimus-R 1.17 (0.85, 1.64) 1.00 (0.78, 1.29) Zotarolimus-R0.83 (0.58, 1.27) Zotarolimus-E (Ref)

24 Bangalore S et al. Circulation 2012:On-line Network Meta-analysis: 1-year Death 77 RCTs, 57,138 pts, 117,762 pt-yrs of FU OR [95% CrI] 0.10 OR (95% Crl) ControlTreatment Favors Control Favors Treatment BMS (Ref) Sirolimus Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 0.97 (0.74, 1.21) 0.97 (0.74, 1.25) 1.28 (0.85, 1.80) 0.66 (0.36, 1.18) 0.87 (0.64, 1.16) Sirolimus (Ref) Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 1.01 (0.80, 1.25) 1.32 (0.88, 1.86) 0.69 (0.40, 1.21) 0.91 (0.69, 1.15) Paclitaxel (Ref) Zotarolimus-E Zotarolimus-R Everolimus 1.28 (0.89, 1.86) 0.67 (0.39, 1.13) 0.88 (0.70, 1.19) Everolimus (Ref) Zotarolimus-E Zotarolimus-R 1.42 (0.97, 2.25) 0.76 (0.47, 1.18) Zotarolimus-E (Ref) Zotarolimus-R0.52 (0.27, 0.98)

25 Bangalore S et al. Circulation 2012:On-line Network Meta-analysis: 1-year TLR 77 RCTs, 57,138 pts, 117,762 pt-yrs of FU OR [95% CrI] 0.10 OR (95% Crl) ControlTreatment Favors Control Favors Treatment BMS (Ref) Sirolimus Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 0.20 (0.16, 0.25) 0.39 (0.31, 0.49) 0.46 (0.32, 0.65) 0.29 (0.15, 0.60) 0.21 (0.14, 0.29) Sirolimus (Ref) Paclitaxel Zotarolimus-E Zotarolimus-R Everolimus 1.95 (1.60, 2.38) 2.30 (1.67, 3.22) 1.47 (0.74, 3.04) 1.03 (0.75, 1.45) Paclitaxel (Ref) Zotarolimus-E Zotarolimus-R Everolimus 1.18 (0.85, 1.64) 0.76 (0.38, 1.53) 0.53 (0.38, 0.73) Everolimus (Ref) Zotarolimus-E Zotarolimus-R 2.23 (1.45, 3.47) 1.43 (0.78, 2.71) Zotarolimus-R0.64 (0.30, 1.37) Zotarolimus-E (ref)

26 EXAMINATION Trial p = pts with STEMI undergoing PCI within 48  (85% primary PCI within 12  ) were randomized to Xience V EES vs. Vision BMS Stent thrombosis (Def/prob) within 1 year 2.6% 0.9% Definite ST was reduced with Xience V from 1.9% to 0.5%, p=0.01 Sabate M. ESC 2011

27 EES CoCr vs BMS: Lower Def. Stent Thrombosis Evidence from 5 RCT Network Meta-Analyses. ARC Definite Stent Thrombosis: EES CoCr vs. BMS Favors EES CoCr

28 Late ST Rates (30 Days - 1 Year) After DAPT Interruption Subsequent Late ST (ARC Def/Prob) (%) No InterruptionInterruption After 30 Days* 13/35000/292 Interruption After 180 Days* 2/435 Interruption After 90 Days* 1/3782/12720/1570/1470/120 Overall Standard Risk Hermiller, JB, PCR 2010 – In Press JACC Int 2011

29

30 Timing of First DAPT Interruption and Stent Thrombosis Through 12 Months EES Co-Cr Demonstrates 0% Stent Thrombosis Rate After DAPT Interruption from 3 to 12 Months 1 1 in every 6 patients who receive stents may interrupt or discontinue DAPT within 12 months post-PCI Never Interrupted 3 DAPT Interrupted 0-3 Months3-12 Months N=11,156 Combined XIENCE USA, SPIRIT V, XIENCE India. SPIRIT women Palmerini, T. Stent Thrombosis and DAPT Interruption in XIENCE V Real-World Patients. PCR 2012

31 EES Co-Cr Demonstrates Low Stent Thrombosis Rate After DAPT Interruption Between 1-12 Months* Timing of First DAPT Interruption and Subsequent Stent Thrombosis Through 12 Months Never Interrupted DAPT Interrupted 0-1 Month1-12 Months Combined XIENCE USA, SPIRIT V, XIENCE India. SPIRIT women Palmerini, T. Stent Thrombosis and DAPT Interruption in XIENCE V Real-World Patients. PCR 2012

32 DES Progress Evolution of Drug-Eluting Stents: Better than Man’s

33 TCFA Development in Neointimal Hyperplasia is More Common with DES than BMS, and can Rupture Causing Stent Thrombosis and Occlusion Nakazawa G et al. J Am Coll Cardiol 2011;57:1314–22

34 Late Incomplete Apposition in SIRTAX p<0.001 Cook et al Eur Heart J 2012 Late ISA at 8 month IVUS was seen in 39/221 lesions (18%) treated with SES or PES, and was more common with SES

35 Number at risk XIENCE V TAXUS Target lesion failure (%) Months XIENCE V (n=2,458) TAXUS Express (n=1,229) p=0.02 HR [95%CI] = 0.78 [0.63, 0.97] 6.7% 4.0% p=0.001 HR [95%CI] = 0.61 [0.46, 0.81] Δ 2.7% % 9.2% Δ 2.5% p=0.004 HR [95%CI] = 0.71 [0.56, 0.90] SPIRIT IV: Target Lesion years TLF = cardiac death, target vessel MI, or ischemic-driven TLR Stone GW et al. JACC 2011 (abstract) ~2.6%/yr event rate after year 1

36 Outline Introduction Current Data Advances to Date Future Directions Metallic DES Bioabsorbable Polymer Metallic DES with No Polymer Completetly Bioabsorbable DES Conclusions and Summary Introduction Current Data Advances to Date Future Directions Metallic DES Bioabsorbable Polymer Metallic DES with No Polymer Completetly Bioabsorbable DES Conclusions and Summary

37 Persistent Limitations Uncovered stent struts with or without late malapposition (thrombosis) Chronic inflammation due to late foreign body reactions and polymer hypersensitivity Strut fracture Lack of vasomotion Neoatherosclerosis

38 Biolimus-A9 Eluting Stent Biolimus is a semi-synthetic sirolimus analogue with 10x higher lipophilicity and similar potency as sirolimus. Biolimus is immersed at a concentration of 15.6  g/mm into a biodegradable polymer, polylactic acid, and applied solely to the abluminal stent surface by a fully automated process. Biolimus is co-released with polylactic acid and completely desolves into carbon dioxide and water after a 6-9 months period. The stainless steel stent platform has a strut thickness of 120  m with a quadrature link design.

39 LEADERS 5-Year Results Serruys P, et al. J Am Coll Cardiol Intv 2013;6:777–89

40 LEADERS: Definate Stent Thrombosis Serruys P, et al. J Am Coll Cardiol Intv 2013;6:777–89

41 LEADERS: Definate Stent Thrombosis Serruys P, et al. J Am Coll Cardiol Intv 2013;6:777–89 Landmark Analyses at 0-1 and 1-5 years RR (95%CI); p value 0-1 yr: 0.99 ( ); p= yrs: ( ); p=0.003 %

42 Drug-Eluting Technology Progression Conformal Biostable Polymer Abluminal Bioabsorbable Polymer Polymer + Drug Platinum Chromium Platinum Chromium Polymer + Drug Current DES SYNERGY DES Vessel Wall Polymer + Drug BMS on luminal side PLGA bioabsorbable polymer + everolimus on abluminal side of stent Coating weight on 16 mm stent ~200 µg (vs ~675 µg for Xience / Promus) Everolimus elutes over ~3 months (similar to Xience / Promus) PLG absorbs by ~4 months, leaving behind a BMS Abluminal Thin strut (0.0029”) PtCr stent

43 EVOLVE Study Design Randomized 1:1:1 at 29 sites (EU, Australia, New Zealand) SYNERGY N=94 SYNERGY ½ Dose N=99 PROMUS Element N=98 Single-blind, noninferiority design Primary Clinical Endpoint: TLF (TV-CD, TV-MI, or TLR) at 30 days Primary Angiographic Endpoint: In-stent late loss at 6 months Patients with de novo native coronary lesions ≤28 mm in length, RVD ≥2.25 mm ≤ 3.5, %DS >50 (excluded LM disease, CTO, AMI or recent MI)

44 Selectively micro-structured surface holds drug in abluminal surface structures BioFreedom Stent (Biosensors) Hypothesis: Polymer-free drug release via porous-eluting stents may reduce late events caused by polymer stent coatings. Potential advantages Avoid long term late adverse effects that might be attributable to the polymerAvoid long term late adverse effects that might be attributable to the polymer Improved surface integrity since there is no polymer to be sheared or pealed away from the stent strutsImproved surface integrity since there is no polymer to be sheared or pealed away from the stent struts Possible shorter need of dual antiplatelet therapyPossible shorter need of dual antiplatelet therapy Biolimus A9 - lipophilic

45 DFS: Drug Filled Stent (Medtronic) Drug elution controlled by diffusion physics Elution Holes

46 Bioresorbable Vascular Scaffolds (BVS) Igaki-Tamai PLLA Magnesium (eluting paclitaxel) Biotronik Dreams PLLA (w/PDLLA coat eluting everolimus) Abbott Absorb Reva ReSolve Iodinated tyrosine- derivative (eluting sirolimus) Elixir DESolve PPLLA (eluting myolimus)

47 Possible Advantages of BVS Restoration of normal vasomotion, with NO production Restoration of normal shear stress and cyclic strain Restoration of normal vessel curvature Reduced risk of very late polymer reactions Avoidance/resolution of positive remodeling and stent malapposition Avoidance/resolution of late strut fractures Less neoatherosclerosis Un-jailing of side-branches Plaque regression MRI/CT imaging follow-up The emotional appeal of normal vessel architecture

48 What is the Minimum Duration of Radial Scaffolding? What is the Minimum Duration of Radial Scaffolding? After DES Placement, Scaffolding of the Vessel is Only a Transient Need Serruys PW, et al., Circulation 1988; 77: 361. n = 342 patients (n = 93 at 30-day F/U; n = 79 at 60-day F/U; n = 82 at 90-day F/U; n = 88 at 120-day F/U) The lumen appears to stabilize approximately three months after PTCA. p < Quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months

49 ‘Caged’ (Stented) Vessel Delayed Healing  Stent Thrombosis? Benign NIH In-Stent Restenosis Late Acquired Malapposition  Stent Thrombosis? Neo-Atheroma  Stent Thrombosis? * uncovered struts 1 1. Virmani, R. CIT 2010 NIH: NeoIntimal Hyperplasia

50 Potential of a Fully * Bioresorbable Vascular Scaffold Benign NIH In-Scaffold RestenosisPlaque Regression 2 Expansive Remodeling 1 Late Lumen Enlargement Since struts disappear, issues related to very late persistent strut malapposition and chronically uncovered struts become irrelevant 1 Serruys, PW, ACC 2011 / 2 Serruys, PW, et al. Lancet. 2009; 373:

51 Dudek D. ABSORB Cohort B 2-year data, ACC Similar Rates of MACE Compared to Historical XIENCE Data ABSORB Extend Clinical Results - MACE Intent to Treat (ITT) Analysis; Interim Snapshot

52 Post-stenting 6-month24-month Complete strut apposition Late acquired incomplete stent apposition with tissue bridges between fractured struts Corrugated endolumen Smooth endoluminal lining Struts largely disappeared although remnant just visible (arrow) Absorb Trial (BVS cohort A): OCT Results Serruys PW et al. Lancet 2009;373:

53 6 months 60 months The Final Golden tube Sealing and shielding of plaques as a result of scaffold implantation : can the scaffold cap the plaque? … and Late lumen enlargement Presented by PW Serruys at TCT2012, accessed at

54 ABSORB Cohort B Temporal Lumen Dimensional Changes ABSORB Cohort B Serial Analysis* Lumen Area 6.53 mm mm mm 2 n = 33 Scaffold Area  1.7% Lumen Area  7,2% Post-PCI6 Months2 Years Very late lumen enlargement noted from 6 months to 2 years *Serruys, PW., TCT 2011

55 ABSORB Vasomotor Function Testing  in Vessel Diameter (mm) Methergine Acetylcholine (n=15) 6 Months 1 (n=6) (n=19) 12 Months 2 (n=13)(n=9) 24 Months 3 (n=7) Vasodilation Vasoconstriction ABSORB Cohort B1 ABSORB Cohort B2 ABSORB Cohort A (pre-drug infusion to post-drug infusion) 1.Adapted from Serruys, PW. ACC Adapted from Serruys, PW. ACC Adapted from Serruys, PW, et al. Lancet 2009; 373:

56 Outline Introduction Current Data Advances to Date Future Directions Metallic DES Bioabsorbable Polymer Metallic DES with No Polymer Completetly Bioabsorbable DES Conclusions and Summary Introduction Current Data Advances to Date Future Directions Metallic DES Bioabsorbable Polymer Metallic DES with No Polymer Completetly Bioabsorbable DES Conclusions and Summary

57 Conclusions: Current and future directions in stenting Current DES have appreciably improved safety and efficacy profiles in ACS and stable CAD compared to first generation devices By utilizing small amounts of a bioabsorbable polymer, polymer-free systems, or fully bioresorbable scaffolds, future generation DES will likely further reduce stent thrombosis and improve late outcomes

58 The Bar is High – For Advanced Devices

59 Thanks for your attention!


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