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Drug-Eluting Stents

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Long Acting Injections and Implants

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Coronary stenting is currently the dominant and most cost-effective interventional approach in managing symptomatic artery diseases. Stent restenosis is the phenomenon of arterial vessel re-narrowing following an angioplasty procedure and is the most common complication of the stenting procedure. Drug-eluting stents (DES) nearly eliminate stent restenosis in simple lesions and significantly reduce its incidence in complex lesions. This chapter provides an overview of the pathophysiology of restenosis and the various considerations that go into the design and development of a successful DES including stent platform and materials, drug carriers, selections of various classes of anti-restenotic agents, and the appropriate modulation of drug load and release duration. Detailed examinations of the leading marketed drug-eluting stents are provided, followed by a brief introduction to devices that are in the development stage which may become the next-generation DES.

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References

  1. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P (1994) A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med 331(8):489–95

    Article  PubMed  CAS  Google Scholar 

  2. Erbel R, Haude M, Hopp HW, Franzen D, Rupprecht HJ, Heublein B, Fischer K, de Jaegere P, Serruys P, Rutsch W, Probst P (1998) Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. Restenosis Stent Study Group. N Engl J Med 339:1672–1688

    Article  PubMed  CAS  Google Scholar 

  3. Fattori R, Piva T (2003) Drug eluting stents in vascular intervention. Lancet 361(9353):247–249

    Article  PubMed  Google Scholar 

  4. Morice MC, Serruys PW, Sousa JE, Fajadet J, Hayashi EB, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R (2002) A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 346:1773–80

    Google Scholar 

  5. Stone GW, Ellis SG, Cox DA, Hermiller J, O’Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenberg J, Popma JJ, Russell ME (2004) A polymer-based paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 350:221–231

    Article  PubMed  CAS  Google Scholar 

  6. Caixeta A, Leon MB, Lansky AJ, Nikolsky E, Aoki J, Moses JW, Schofer J, Morice M, Schampaert E, Kirtane AJ, Popma JJ, Parise H, Fahy M, Mehran R (2009) 5-Year Clinical Outcomes After Sirolimus-Eluting Stent Implantation: Insights From a Patient-Level Pooled Analysis of 4 Randomized Trials Comparing Sirolimus-Eluting Stents With Bare-Metal Stents. J Am Coll Cardiol 54:894–902. doi:10.1016/j/jack.2009.04.077

    Article  PubMed  Google Scholar 

  7. Eisenstein EL, Wijns W, Fajadet J, Mauri L, Edwards R, Cowper PA, Kong DF, Anstrom KJ (2009) Long-term clinical and economic analysis of the endeavor drug-eluting stent versus the driver bare-metal stent: 4-year results from the ENDEAVOR II Trial (randomized controlled trial to evaluate the safety and efficacy of the medtronic AVE ABT-578 eluting driver coronary Stent in De Novo native coronary artery lesions). J Am Coll Cardiol Intv 2:1178–1187. doi:10.1016/j.jcin.2009.10.011

    Google Scholar 

  8. Garg S, Serruys P, Onuma Y, Dorange C, Veldhof S, Miguel-Hebert K, Sudhir K, Boland J, Huber K, Garcia E, te Riele JAM (2009) 3-Year Clinical Follow-Up of the XIENCE V Everolimus-Eluting Coronary Stent System in the Treatment of Patients With De Novo Coronary Artery Lesions: The SPIRIT II Trial (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions). J Am Coll Cardiol Cardiovasc Interv 2(12):1190–1198

    Google Scholar 

  9. Vermani R, Kolodgie FD, Farb A (2004) Drug-eluting stents: are they really safe? Am Heart Hosp J 2:85–88

    Article  Google Scholar 

  10. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R (2006) Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 48(1):193–202

    Article  PubMed  Google Scholar 

  11. Spaulding C (2008) The Question of Drug-eluting Stent Safety: Then and Now. Am J Cardiol 102(9 Suppl):12j–17j. doi:10.1016/j.amjcard.2008.09.004

    Article  PubMed  CAS  Google Scholar 

  12. Scott NA (2006) Restenosis following implantation of bare metal coronary stents: Pathophysiology and pathways involved in the vascular response to injury. Adv Drug Deliv Rev 58(3):358–376

    Article  PubMed  CAS  Google Scholar 

  13. Sousa JE, Serruys PW, Costa MA (2003) New frontiers in cardiology: Drug-eluting stents: Part 1. Circulation 107:2274–2279

    Article  PubMed  Google Scholar 

  14. Beyar R, Roguin A (2001) The sirolimus coated stent: will the achilles heel of interventional cardiology finally be cured? Eur Heart J 22:2054–2057. doi:10.1053/euhj.2001.2950

    Article  PubMed  CAS  Google Scholar 

  15. Liuzzo JP, Ambrose JA, Coppola JT (2005) Sirolimus- and taxol-eluting stents differ towards intimal hyperplasia and re-endothelialization. J Invasive Cardiol 17:497–502

    PubMed  Google Scholar 

  16. Formica RN, Lorber KM, Friedman AL, Bia MJ, Smith JD, Lorber MI (2004) The evolving experience using everolimus in clinical transplantation. Transplant Proc 36:495S–499S

    Article  PubMed  CAS  Google Scholar 

  17. Hamada N, Miyata M, Eto H, Shirasawa T, Akasaki Y, Nagaki A, Tei C (2010) Tacrolimus-eluting stent inhibits neointimal hyperplasia via calcineurin/NFAT signaling in porcine coronary artery model. Atherosclerosis 208(1):97–103

    Article  PubMed  CAS  Google Scholar 

  18. Gummert JF, Ikonen T, Morris RE (1999) Newer immunosuppressive drugs: A review. J Am Soc Nephrol 10:1366–1380

    PubMed  CAS  Google Scholar 

  19. Straubinger RM, Sharma A, Murray M, Mayhew E (1993) Novel taxol formations: Taxol-containing liposomes”. J Natl Cancer Inst Monogr 15:69–78

    PubMed  Google Scholar 

  20. Jordan MA, Toso RJ, Thrower D, Wilson L (1993) Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci USA 90(2):9552–9556

    Article  PubMed  CAS  Google Scholar 

  21. Wohrle J, Al-Khayer E, Grotzinger U, Schindler C, Kochs M, Hombach V, Hoher M (2001) Comparison of the heparin coated vs the uncoated Jostent – no influence on restenosis or clinical outcome. Eur Heart J 22(19):1808–1816

    Article  PubMed  CAS  Google Scholar 

  22. Abizaid A, Albertal M, Costa MA, Abizaid AS, Staico R, Feres F, Mattos LA, Sousa AGMR, Moses J, Kipshidize N, Roubin GS, Mehran R, New G, Leon MB, Sousa JE (2004) First Human Experience with the 17-beta-estradiol-eluting Stent: The estrogen and stents to eliminate restenosis (EASTER) trial. J Am Coll Cardiol 43:1118–1121. doi:10.1016/j.jacc.2004.01.023

    Article  PubMed  CAS  Google Scholar 

  23. New G, Moses JW, Roubin GS, Leon MB, Colombo A, Iyer SS, Tio FO, Mehran R, Kipshidze N (2002) Estrogen-eluting, phosphorylcholine-coated stent implantation is associated with reduced neointimal formation but no delay in vascular repair in a porcine coronary model. Catheter Cardio Interv 57(2):266–271

    Article  Google Scholar 

  24. Geraldes P, Sirois MG, Bernatchez PN, Tanquay J (2002) Estrogen regulation of endothelial and smooth muscle cell migration and proliferation: Role of p38 and p42/44 mitogen-activated protein kinase. Arterioscler Thromb Vasc Biol 22:1585–1590

    Article  PubMed  CAS  Google Scholar 

  25. Rogers CD (2002) Drug-eluting stents: role of stent design, delivery vehicle, and drug selection. Rev Cardiovasc Med 3(Suppl 5):S10–S15

    Google Scholar 

  26. Fischell T, Dishmon D, Elhaddi A, Alsafwah S, Mannem S (2009) The perfect drug-eluting stent. Card Inter Today, June/July, pp 29–36

    Google Scholar 

  27. McClean DR, Eigler NL (2002) Stent design: implications for restenosis. Rev Cardiovasc Med 3(suppl 5):S16–S22

    Google Scholar 

  28. Gopinath M, Feldman MD, Patel D, Agrawal CM (2007) Coronary stents: A materials perspective. Biomaterials 28(9):1689–1710

    Article  Google Scholar 

  29. Lansky AJ, Costa RA, Mintz GS, Tsuchiya Y, Midei M, Cox DA, O’Shaughnessy C, Applegate RA, Cannon LA, Mooney M, Farah A, Tannenbaum MA, Yakubov S, Kereiakes DJ, Wong SC, Kaplan B, Cristea E, Stone GW, Leon MB, Knopf WD, O’Neill WW (2004) Non-polymer-based paclitaxel-coated coronary stents for the treatment of patients with de novo coronary lesions. Circulation 109:1948–1954

    Article  PubMed  CAS  Google Scholar 

  30. Minghetti P, Cilurzo F, Selmin F, Casiraghi A, Grignani A, Montanari L (2009) Sculptured drug-eluting stent for the on-site delivery of tacrolimus. Eur J Pharm Biopharm 73(3):331–336

    Article  PubMed  CAS  Google Scholar 

  31. Joung YK, Kim H, Kim S, Chung KH, Jang Y, Park KD (2003) Estrogen release from metallic stent surface for the prevention of restenosis. J Control Release 92:83–91

    Article  PubMed  CAS  Google Scholar 

  32. Verheye S, Markou CP, Salame MY, Wan B, King SB, Robinson KA, Chronos NAF, Hanson SR (2000) Reduced thrombus formation by hyaluronic acid coating of endovascular devices. Arterioscler Thromb Vasc Biol 20:168

    Article  Google Scholar 

  33. Chen MC, Liang HF, Chiu YL, Yen C, Wei H, Sung H (2005) A novel drug-eluting stent spray coated with multi-layers of collagen and sirolimus. J Control Release 108:178–189. doi:10.1016/j.jconrel.2005.07.022

    Article  PubMed  CAS  Google Scholar 

  34. Farb A, Heller PF, Shroff S, Cheng L, Kolodgie FD, Carter AJ, Scott DS, Froehlich J, Virmani R (2001) Pathological Analysis of Local Delivery of Paclitaxel Via a Polymer-Coated Stent. Circulation 104:473–479

    Article  PubMed  CAS  Google Scholar 

  35. Kamath K, Barry JJ, Miller KM (2006) The TAXUS drug-eluting stent: A new paradigm in controlled drug delivery. Adv Drug Deliv Rev 58:412–436

    Article  PubMed  CAS  Google Scholar 

  36. Jabara R, Chronos N, Conway D, Molema W, Robinson K (2008) Evaluation of a novel slow-release paclitaxel-eluting stent with a bioabsorbable polymeric surface coating. J Am Coll Cardiol Cardiovasc Interv 1(1):81–87

    Google Scholar 

  37. Turco A, Simonton CA, Verheye S et al (2008) A novel bioresorbable polymer paclitaxel-eluting stent for the treatment of single and multivessel coronary disease: primary results of the COSTAR (cobalt chromium stent with antiproliferative for restenosis) II study. J Am Coll Cardiol 51:1543–1552

    Article  PubMed  Google Scholar 

  38. Meredith IT (2008) A Critical Appraisal of “Next” Generation DES: Will They Be Safer and As Effective? CIT, Beijing

    Google Scholar 

  39. Falotico R, Parker T, Grishaber R, Price S, Cohen S, Rogers C (2009) NEVO: a new generation of sirolimus-eluting coronary stent. Eurointervention 5:F88–F93

    Article  PubMed  Google Scholar 

  40. Grube E (2009) Bioabsorbable stents: The Boston Scientific and REVA Technology. EuroPCR

    Google Scholar 

  41. Ormiston J, Serruys P, Regar E, Dudek D, Thuesen L, Webster MW, Onuma Y, Garcia-Garcia HM, McGreevy R, Veldhof S (2008) A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet 371(9616):899–907

    Article  PubMed  CAS  Google Scholar 

  42. Cronstein BN, Kimmel SC, Levin RI, Martiniuk F, Weissmann G (1992) A mechanism for the antiinflammatory effects of corticosteroids: The glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Proc Natl Acad Sci USA 89:9991–9995

    Article  PubMed  CAS  Google Scholar 

  43. CYPHER® Stents Instruction for Use, http://www.cordislabeling.com/pdf/5462872_4.pdf. Accessed on March 20, 2010

  44. Garcia-Touchard A, Burke SE, Toner JL, Cromack K, Schwartz RS (2006) Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks. Eur Heart J 27(8):988–993

    Article  PubMed  CAS  Google Scholar 

  45. Hezi-Yamit A, Sullivan C, Wong J, David L, Chen M, Cheng P, Shumaker D, Wilcox JN, Udipi K (2009) Impact of polymer hydrophilicity on biocompatibility: Implication for DES polymer design. J Biomed Mater Res A 90(1):133–141

    PubMed  Google Scholar 

  46. Holmes DR, Camrud AR, Jorgenson MA, Edwards WD, Schwartz RS (1994) Polymeric stenting in the porcine coronary artery model: differential outcome of exogenous fibrin sleeves versus polyurethane-coated stents. J Am Coll Cardiol 24:525–531

    Article  PubMed  CAS  Google Scholar 

  47. Rose SF, Lewis AL, Hanlon GW, Lloyd AW (2003) Biological responses to cationically charged phosphorylcholine-based materials in vitro. Biomaterials 25:5125–5135

    Article  Google Scholar 

  48. TAXUS® Direction for use, http://www.bostonscientific.com/Device.bsci?page=ResourceDetail&navRelId=1000.1003&method=DevDetailHCP&id=10005691&resource_type_category_id=1&resource_type_id=82&pageDisclaimer=Disclaimer. ProductPage. Accessed on March 20, 2010

  49. XIENCE™ Instruction for Use, http://www.abbottvascular.com/en_US/content/document/eIFU_XIENCEV.pdf

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Correspondence to Lori Alquier .

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© 2012 Controlled Release Society

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Zhao, J., Alquier, L. (2012). Drug-Eluting Stents. In: Wright, J., Burgess, D. (eds) Long Acting Injections and Implants. Advances in Delivery Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0554-2_19

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