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New Drug-Eluting Stents

New Drug-Eluting Stents. Soo-Joong Kim M.D., PhD. Department of Cardiology, Internal Medicine, Kyung Hee University Medical Center. Drug-Eluting Stents. Impressive clinical benefits Safety concerns : stent thrombosis patient factors lesion factors

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New Drug-Eluting Stents

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  1. New Drug-Eluting Stents Soo-Joong Kim M.D., PhD. Department of Cardiology, Internal Medicine, Kyung HeeUniversity Medical Center

  2. Drug-Eluting Stents • Impressive clinical benefits • Safety concerns : stent thrombosis • patient factors • lesion factors • stent polymer : focal area for new research & stent development

  3. 3 components of DES Drug Stent platform Polymer

  4. The second-generation DES • more biocompatible polymers • impressive safety results at medium-term follow-up • concerns for a nonerodablepolymer • persistent arterial wall inflammation • delayed vascular healing  precipitating ST and delayed restenosis

  5. New DES • Development of DES coated with biodegradable polymers. • attractive combination of controlled drug elution in parallel with biodegradation of the polymer into inert monomers • after complete biodegradation • Only BMS remains • Reducing long-term risks a/w permanent polymer • Stents completely free of polymer, • BMS coated in novel coatings • Completely biodegradable magnesium and polymeric stents • completely disappear once vascular healing has taken place.

  6. Metallic DES with Durable Polymer

  7. Metallic DES with Durable Polymer • new durable polymer • new polymer technology • new antiproliferative agents • new metal stent platforms

  8. Metallic DES with Durable Polymer • New polymer technology • Endeavor Resolute • Driver cobalt chromium stent platform • Biolinx polymer : a blend of 3 different polymers: • the hydrophobic C10 polymer to control drug release • the biocompatible and hydrophilic C19 polymer • polyvinyl pyrrolidone (early burst of drug release) • Delayed drug release : at least 85% of the zotarolimus released within 60 days, with the remainder released within 180 days • match the delayed healing times seen in complex lesions

  9. Endeavor Resolute Stent

  10. Endeavor Resolute Metallic DES with Durable Polymer • 139 pts, multicenter, nonrandomized, FIM • angiographic in-stent late loss of 0.22 mm at 9 M f/up • and respective rates of MACE, TLR, & any ST : 8.6%, 0.7%, & 0.0% at 12 M f/up 11.6%, 1.6%, 0.0%% at 3-year f/up • RESOLUTE All-Comers trial • 2,300 pts, • randomized in a 1:1 ratio either R-ZES or the Xience V • At 12-months clinical follow-up, noninferior to EES with respect to the primary clinical end point of target lesion failure, a composite of cardiac death, target vessel MI & clinically indicated TLR (ZES 8.2% vs. EES 8.3%, pnoninferiority <0.001)

  11. Definite or probable ST : 18 (1.6%) vs 8 (0.7%), p=0.05 Definite or probable orpossible : 26 (2.3%) vs 17 (1.5%), p=0.17

  12. Metallic DES with Durable Polymer • New antiproliferative agents • Elixir DESynenovolimus-eluting stent (NES) • Cobalt chromium stent platform • a durable poly(n-butyl methacrylate) polymer (similar to Cyphersirolimus-eluting stent) • a drug coating of novolimus : mTOR inhibitor (metabolite of sirolimus) • a similar efficacy to currently available agents • lower drug dose (NES 5 g/mm of stent length vs. ZES 10 g/mm) • lower polymer load (polymer thickness <3 μm vs. 4.1 m on ZES)

  13. Elixir DESyne NES

  14. 15-pts FIM EXCELLA (Elixir Medical Clinical Evaluation of the Novolimus-Eluting Coronary Stent System) study • Angiographic in-stent late loss of 0.31± 0.25 mm • % volume obstruction IVUS of 6.0 ± 4.4% at 8 M f/up • No MACE through 12 M & 1 MACE event at 24M • single-blind, prospective EXCELLA-II study, • Randomized 210 pts either NES (n = 139) or or ZES (n = 71) • At 9 M f/up, the primary end point of angiographic in-stent late loss : 0.11 ± 0.32 mm and 0.63 ± 0.42 mm (pnoninferiority< 0.0001, psuperiority <0.0001) • During clinical follow-up, no significant differences between stent groups in the device-orientated composite end point (NES 2.9% vs. ZES 5.6%, p= .45)

  15. EXCELLA study

  16. % volume obstruction IVUS of 6.0 ± 4.4% at 8 M f/up

  17. 15-pts FIM EXCELLA (Elixir Medical Clinical Evaluation of the Novolimus-Eluting Coronary Stent System) study • Angiographic in-stent late loss of 0.31± 0.25 mm • % volume obstruction IVUS of 6.0 ± 4.4% at 8 M f/up • No MACE through 12 M & 1 MACE event at 24M • single-blind, prospective EXCELLA-II study, • Randomized 210 pts either NES (n = 139) or or ZES (n = 71) • At 9 M f/up, the primary end point of angiographic in-stent late loss : 0.11 ± 0.32 mm and 0.63 ± 0.42 mm (pnoninferiority< 0.0001, psuperiority <0.0001) • During clinical follow-up, no significant differences between stent groups in the device-orientated composite end point (NES 2.9% vs. ZES 5.6%, p= .45)

  18. Metallic DES with Durable Polymer • New metal stent platforms • Platinum chromium Element stent Platform • Platinum chromium : twice as dense as iron or cobalt chromium  much greater radio-opacity. increased radial strength  thinner stent struts  reduce clinical and angiographic restenosis • strut thickness of 81 μm compared with 96 μm for the TAXUS Liberté,

  19. Platinum chromium EES Element Stent

  20. PLATINUM QCA StudyPrespecified Efficacy Endpoint9-Month In-Stent Late Loss – Workhorse Lesions 0.6 Performance Goal = 0.44 mm 0.4 In-stent Late Loss (QCA) in Workhorse Lesions (mm) P < 0.001 0.2 0.170.25 mm*(N=73) 0.0 Workhorse lesions: RVD ≥2.5–≤4.25 mm, lesion length ≤24 mm * Mean ±SD; value of 0.17 with an upper confidence bound of 0.22 mm is significantly less (P<0.001) than performance goal based on historical TAXUS Express value (0.41 mm + delta [0.03 mm]); QCA=quantitative coronary angiography Presented by Ian Meredith, MBBS, PhD at TCT 2010.

  21. PLATINUM QCA Study Clinical Outcomes through 9 Months 30 Days 9 Months N=100 One patient had a periprocedural ST with TLR & non-target lesion TVR * Ischemia-driven TLR, or MI/cardiac death related to the target vessel Presented by Ian Meredith, MBBS, PhD at TCT 2010.

  22. 1,532 pts in the randomized multicenter PLATINUM (A Prospective, Randomized, Multicenter Trial to Assess an Everolimus-Eluting Coronary Stent System [PROMUS Element] for the Treatment of up to Two De Novo Coronary Artery Lesions) compared with the cobalt chromium Promus EES • Two parallel subtrials to evaluate the Promus Element stent in small vessels and in long lesions.

  23. TAXUS Element stent Metallic DES with Durable Polymer • PERSEUS (A Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System for the Treatment of De Novo Coronary Artery Lesions) • The noninferiority PERSEUS Workhorse trial • randomized, in a 3:1 ratio, 1,262 pts with lesions < 28 mm vessels (2.75 to 4.0 mm) into the TAXUS Element (n 942) or the TAXUS Express PES (n 320) • At 9 M angiographic follow-up, no significant difference in late loss between the Element and Express stents (Element 0.34 ± 0.55 mm vs. Express 0.26 ± 0.52 mm, p = 0.33). • The rate of the primary end point of target lesion failure at 12 months : 5.6%, & 6.1% (p=0.78) • no significant differences in the clinical end points of MACE, mortality, MI, and ST.

  24. TAXUS Element stent Metallic DES with Durable Polymer • PERSEUS (A Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System for the Treatment of De Novo Coronary Artery Lesions) • The superiority PERSEUS Small Vessel trial, • compared the TAXUS Element stent to historical BMS • 349 pts with lesions 20 mm in length, vessels (2.25 to 2.75) • at 9 M f/up, a significantly lower primary end point of in-stent late loss with the Element stent compared with the BMS stent (0.38 ± 0.51 mm vs. 0.80 ± 0.53 mm, p < 0.001) • At 12 M f/up, the rates of target lesion failure and MACE were both significantly lower with the Element stent, • ST were comparable between both stents.

  25. DES with Biodegradable Polymer

  26. DES with Biodegradable Polymer • 1. antirestenotic benefits of a standard DES, 2. once the polymer has biodegraded, they speculatively may offer the safety benefits of a BMS • 1. optimal biocompatibility, composition, formulation, and degradation time of the polymer. 2. pharmacokinetics of the antiproliferative agent released by the degradation of the polymer. 3. variation in polymer degradation time

  27. DES with Biodegradable Polymer • clinical advantage of stents with biodegradable polymers is currently hypothetical. • Clinical study limited by short-term follow-up, and definitive data on the long-term benefits are lacking. • Polymer breakdown can be associated with a significant inflammatory reaction(acidic environment) • persistent immune response to monomer breakdown products

  28. DES with Biodegradable Polymer • Myolimus based • Myolimus-eluting stent • Palitaxel based • Infinnium stent • Jactax stent • Synergy stent • Sirolimus based • Supralimus stent • Excel stent • Nevo stent • Biolimus A9 based • Biomatrix stent • Nobori stent • Axxess stent • Xtent custom NX stent

  29. Supralimus stent • stainless steel SES with a biodegradable polymer mix of poly-L-lactide (PLA), poly vinyl pyrrolidone, poly lactide-co-caprolactone, and poly lactideco-glycolide (PLGA). • 1/2 of the sirolimus eluted by day 9, with elution being complete within 48 days. • the polymer, on the other hand, completely biodegrades within 7 months.

  30. Supralimus stent • 100 pts SERIES I (Study of the SupralimusSirolimus Eluting Stent in the Treatment of Patients With Real World Coronary Artery Lesions) FIM study • in-stent angiographic restenosis of 0.0% • late loss of 0.09 ± 0.37 mm at 6 M. • At 30 M, the rate of TVR 4%, with no definite ST • eSERIES multicenter registry (6M f/up) • over 1.100 pts, similar clinical effectiveness & safety at 6M • Supralimus stent vsInfinnium PES vs BMS in the randomized, multicenter PAINT (Percutaneous Intervention With Biodegradable-Polymer Based Paclitaxel- Eluting, Sirolimus-Eluting, or Bare Stents for the Treatment Of De Novo Coronary Lesions) study of 274 low-risk patients.

  31. PAINT Angiographic Findings at Baseline, Post-Procedure and 9 Months

  32. PAINT Clinical Outcomes After 12 Months of Follow-Up No differences in the risk of death, infarction, or stent thrombosis among the study groups.

  33. SERIES III (ongoing) • noninferiority trial • randomize 400 pts to either Xience V or Supralimus • the primary end point of 9-month in-stent late loss.

  34. Nevo stent • open-cell, cobalt chromium with a PLGA biodegradable polymer and sirolimus elution • polymer and sirolimus are contained within reservoirs : • eliminates need for a surface polymer coating, thereby reducing tissue–polymer contact by over 75% • cf. Costar stent

  35. Nevo stent design

  36. NEVO stent • NEVO-RES I (NEVO RES-ELUTION) study • randomized, multicenter, noninferiority study • NEVO vs TAXUS Liberté PES stent in 394 patients with single de novo coronary artery lesions. • At 6M angiographic f/up, the primary end point of in-stent late lumen loss significantly lower in NEVO stent (0.13 mm vs. 0.36 mm, p<0.0001) • a superiority preserved irrespective of DM, lesion length, or vessel diameter • Clinical end points at both 6 & 12 M numerically lower in the NEVO-treated group, • The rate of ST was 0.0% (NEVO) and 1.1% (p = 0.24) • NEVO II and NEVO III in future trials

  37. NEVO-RES I (NEVO RES-ELUTION) study

  38. Biolimus A9 based stent • highly lipophilicsirolimus analogue • combined with an abluminal PLA biodegradable polymer on a number of different stent platforms. • polymer biodegrades within 6 to 9 M • abluminal location of polymer • more targeted tissue release • reduced systemic exposure. • encouraging clinical results

  39. Biomatrix stent The elution pattern of Biolimus A9 & corresponding biodegradation pattern of the poly-lactic acid (PLA) polymer.

  40. Biomatrix stent • all-comers LEADERS (Limus Eluted from A Durable versus Erodable Stent coating) trial • BiomatrixvsCypher in 1.707 pts in randomization • noninferior for MACE, a composite of cardiac death, MI, and ischemia driven TVR at 12 M f/up (Biomatrix 10.6% vs. Cypher 12.0%, p = 0.37) • preservation of this noninferiority at 2-year follow-up • stent’s PLA polymer completely biodegraded by 9 M • fewer very late ST events (1 year) with the Biomatrix stent (0.2% vs. 0.5%)

  41. 15 Risk Difference -1.3%, Upper Limit 95% CI 1.1% Pnon-inferiority = 0.003 Sirolimus Stent 10.5% 10 Cumulative Incidence (%) Biolimus Stent 9.2% 5 Rate Ratio = 0.88, 95% CI 0.64 - 1.19 0 0 1 2 3 4 5 6 7 8 9 Months of Follow-up No. at risk BES 857 806 798 796 792 784 779 777 771 761 SES 850 791 786 784 781 777 771 758 751 746 LEADERS: Primary EndpointCardiac Death, MI, or TVR @ 9 months

  42. Biolimus A9 based stent • OCT substudy • higher rate of near complete (95%) strut coverage with the Biomatrix stent (vsCypher SES at 9M follow-up (89.3% vs. 63.3%, p 0.03)

  43. Nobori stent

  44. Nobori stent • NOBORI CORE study • late loss at 9 M f/up in 99 patients randomized to NoborivsCypher SES : 0.10 mm vs 0.12 mm, (p= 0.66) • significantly better recovery of endothelial function with the Nobori • Nobori I study • Randomized 243 patients to Nobori stent (n=153) vs TAXUS stent (n= 90) • at 9 M, noninferiority, and subsequent superiority, of the Nobori stent with respect to late loss (0.11 mm vs. 0.32 mm, pnoninferiority <0.001, psuperiority < 0.001) • ST at 9M lower with the Nobori stent (0.0% vs. 2.2%)

  45. NOBORI CORE

  46. Nobori stent • NOBORI CORE study • late loss at 9 M f/up in 99 patients randomized to NoborivsCypher SES : 0.10 mm vs 0.12 mm, (p= 0.66) • significantly better recovery of endothelial function with the Nobori • Nobori I study • Randomized 243 patients to Nobori stent (n=153) vs TAXUS stent (n= 90) • at 9 M, noninferiority, and subsequent superiority, of the Nobori stent with respect to late loss (0.11 mm vs. 0.32 mm, pnoninferiority <0.001, psuperiority < 0.001) • ST at 9M lower with the Nobori stent (0.0% vs. 2.2%)

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