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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
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
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
Fattori R, Piva T (2003) Drug eluting stents in vascular intervention. Lancet 361(9353):247–249
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
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
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
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
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
Vermani R, Kolodgie FD, Farb A (2004) Drug-eluting stents: are they really safe? Am Heart Hosp J 2:85–88
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
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
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
Sousa JE, Serruys PW, Costa MA (2003) New frontiers in cardiology: Drug-eluting stents: Part 1. Circulation 107:2274–2279
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
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
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
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
Gummert JF, Ikonen T, Morris RE (1999) Newer immunosuppressive drugs: A review. J Am Soc Nephrol 10:1366–1380
Straubinger RM, Sharma A, Murray M, Mayhew E (1993) Novel taxol formations: Taxol-containing liposomes”. J Natl Cancer Inst Monogr 15:69–78
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
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
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
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
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
Rogers CD (2002) Drug-eluting stents: role of stent design, delivery vehicle, and drug selection. Rev Cardiovasc Med 3(Suppl 5):S10–S15
Fischell T, Dishmon D, Elhaddi A, Alsafwah S, Mannem S (2009) The perfect drug-eluting stent. Card Inter Today, June/July, pp 29–36
McClean DR, Eigler NL (2002) Stent design: implications for restenosis. Rev Cardiovasc Med 3(suppl 5):S16–S22
Gopinath M, Feldman MD, Patel D, Agrawal CM (2007) Coronary stents: A materials perspective. Biomaterials 28(9):1689–1710
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
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
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
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
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
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
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
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
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
Meredith IT (2008) A Critical Appraisal of “Next” Generation DES: Will They Be Safer and As Effective? CIT, Beijing
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
Grube E (2009) Bioabsorbable stents: The Boston Scientific and REVA Technology. EuroPCR
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
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
CYPHER® Stents Instruction for Use, http://www.cordislabeling.com/pdf/5462872_4.pdf. Accessed on March 20, 2010
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
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
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
Rose SF, Lewis AL, Hanlon GW, Lloyd AW (2003) Biological responses to cationically charged phosphorylcholine-based materials in vitro. Biomaterials 25:5125–5135
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
XIENCE™ Instruction for Use, http://www.abbottvascular.com/en_US/content/document/eIFU_XIENCEV.pdf
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Controlled Release Society
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/978-1-4614-0554-2_19
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-0553-5
Online ISBN: 978-1-4614-0554-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)