Skip to main content
SpringerLink
Log in

Histopathology of vascular response to drug-eluting stents: an insight from human autopsy into daily practice

  • Review Article
  • Published:
Cardiovascular Intervention and Therapeutics Aims and scope Submit manuscript

Abstract

Drug-eluting stents (DES) were developed with the primary purpose of inhibiting neointimal overgrowth following percutaneous coronary intervention (PCI). While DES have significantly reduced the rates of restenosis compared with bare metal stent (BMS), they have not completely eliminated it. Moreover, late stent thrombosis (LST), attributed to delayed arterial healing or abnormal vessel responses to DES, have emerged as a major safety concern. Although newer DES or other novel devices are expected to show promising results, the problems in interventional technologies have not been completely resolved. In this review, we will consider the current status of DES in clinical practice and discuss the strengths and limitations of recent advances from the view of histopathology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Farb A, Sangiorgi G, Carter AJ, Walley VM, Edwards WD, Schwartz RS, Virmani R. Pathology of acute and chronic coronary stenting in humans. Circulation. 1999;99:44–52.

    Article  CAS  PubMed  Google Scholar 

  2. Naito M, Stirk CM, Smith EB, Thompson WD. Smooth muscle cell outgrowth stimulated by fibrin degradation products. The potential role of fibrin fragment e in restenosis and atherogenesis. Thromb Res. 2000;98:165–74.

    Article  CAS  PubMed  Google Scholar 

  3. Farb A, Weber DK, Kolodgie FD, Burke AP, Virmani R. Morphological predictors of restenosis after coronary stenting in humans. Circulation. 2002;105:2974–80.

    Article  PubMed  Google Scholar 

  4. Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–26.

    Article  CAS  PubMed  Google Scholar 

  5. Sata M, Saiura A, Kunisato A, Tojo A, Okada S, Tokuhisa T, Hirai H, Makuuchi M, Hirata Y, Nagai R. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med. 2002;8:403–9.

    Article  CAS  PubMed  Google Scholar 

  6. Farb A, Kolodgie FD, Hwang JY, Burke AP, Tefera K, Weber DK, Wight TN, Virmani R. Extracellular matrix changes in stented human coronary arteries. Circulation. 2004;110:940–7.

    Article  CAS  PubMed  Google Scholar 

  7. Kimura T, Yokoi H, Nakagawa Y, Tamura T, Kaburagi S, Sawada Y, Sato Y, Hamasaki N, Nosaka H, et al. Three-year follow-up after implantation of metallic coronary-artery stents. N Engl J Med. 1996;334:561–6.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  9. Napoli C, de Nigris F, Williams-Ignarro S, Pignalosa O, Sica V, Ignarro LJ. Nitric oxide and atherosclerosis: an update. Nitric Oxide. 2006;15:265–79.

    Article  CAS  PubMed  Google Scholar 

  10. Anderson PG, Bajaj RK, Baxley WA, Roubin GS. Vascular pathology of balloon-expandable flexible coil stents in humans. J Am Coll Cardiol. 1992;19:372–81.

    Article  CAS  PubMed  Google Scholar 

  11. Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. 2007;115:2435–41.

    Article  PubMed  Google Scholar 

  12. Nakazawa G, Finn AV, Joner M, Ladich E, Kutys R, Mont EK, Gold HK, Burke AP, Kolodgie FD, Virmani R. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. Circulation. 2008;118:1138–45.

    Article  PubMed  Google Scholar 

  13. Hwang CW, Wu D, Edelman ER. Physiological transport forces govern drug distribution for stent-based delivery. Circulation. 2001;104:600–5.

    Article  CAS  PubMed  Google Scholar 

  14. Takebayashi H, Mintz GS, Carlier SG, Kobayashi Y, Fujii K, Yasuda T, Costa RA, Moussa I, Dangas GD, Mehran R, Lansky AJ, Kreps E, Collins MB, Colombo A, Stone GW, Leon MB, Moses JW. Nonuniform strut distribution correlates with more neointimal hyperplasia after sirolimus-eluting stent implantation. Circulation. 2004;110:3430–4.

    Article  CAS  PubMed  Google Scholar 

  15. Nakano M, Otsuka F, Yahagi K, Sakakura K, Kutys R, Ladich ER, Finn AV, Kolodgie FD, Virmani R. Human autopsy study of drug-eluting stents restenosis: histomorphological predictors and neointimal characteristics. Eur Heart J. 2013;34:3304–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, Kolodgie FD, Finn AV, Virmani R. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol. 2011;57:1314–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O, Innerarity TL, Boren J. Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature. 2002;417:750–4.

    Article  CAS  PubMed  Google Scholar 

  18. Windecker S, Remondino A, Eberli FR, Juni P, Raber L, Wenaweser P, Togni M, Billinger M, Tuller D, Seiler C, Roffi M, Corti R, Sutsch G, Maier W, Luscher T, Hess OM, Egger M, Meier B. Sirolimus-eluting and paclitaxel-eluting stents for coronary revascularization. N Engl J Med. 2005;353:653–62.

    Article  CAS  PubMed  Google Scholar 

  19. Simsek C, Magro M, Boersma E, Onuma Y, Nauta S, Daemen J, Gaspersz M, van Geuns RJ, van der Giessen W, van Domburg R, Serruys P. Comparison of six-year clinical outcome of sirolimus- and paclitaxel-eluting stents to bare-metal stents in patients with st-segment elevation myocardial infarction: an analysis of the research (rapamycin-eluting stent evaluated at Rotterdam cardiology hospital) and t-search (taxus stent evaluated at Rotterdam cardiology hospital) registries. J Invasive Cardiol. 2011;23:336–41.

    PubMed  Google Scholar 

  20. Nakazawa G, Finn AV, Vorpahl M, Ladich ER, Kolodgie FD, Virmani R. Coronary responses and differential mechanisms of late stent thrombosis attributed to first-generation sirolimus- and paclitaxel-eluting stents. J Am Coll Cardiol. 2011;57:390–8.

    Article  CAS  PubMed  Google Scholar 

  21. Nakano M, Yahagi K, Otsuka F, Sakakura K, Finn AV, Kutys R, Ladich E, Fowler DR, Joner M, Virmani R. Causes of early stent thrombosis in patients presenting with acute coronary syndrome: an ex vivo human autopsy study. J Am Coll Cardiol. 2014;63:2510–20.

  22. Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie FD. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation. 2004;109:701–5.

    Article  PubMed  Google Scholar 

  23. Farb A, Heller PF, Shroff S, Cheng L, Kolodgie FD, Carter AJ, Scott DS, Froehlich J, Virmani R. Pathological analysis of local delivery of paclitaxel via a polymer-coated stent. Circulation. 2001;104:473–9.

    Article  CAS  PubMed  Google Scholar 

  24. Park DW, Hong MK, Mintz GS, Lee CW, Song JM, Han KH, Kang DH, Cheong SS, Song JK, Kim JJ, Weissman NJ, Park SW, Park SJ. Two-year follow-up of the quantitative angiographic and volumetric intravascular ultrasound analysis after nonpolymeric paclitaxel-eluting stent implantation: late “catch-up” phenomenon from aspect study. J Am Coll Cardiol. 2006;48:2432–9.

    Article  CAS  PubMed  Google Scholar 

  25. Nakagawa Y, Kimura T, Morimoto T, Nomura M, Saku K, Haruta S, Muramatsu T, Nobuyoshi M, Kadota K, Fujita H, Tatami R, Shiode N, Nishikawa H, Shibata Y, Miyazaki S, Murata Y, Honda T, Kawasaki T, Doi O, Hiasa Y, Hayashi Y, Matsuzaki M, Mitsudo K. Incidence and risk factors of late target lesion revascularization after sirolimus-eluting stent implantation (3-year follow-up of the j-cypher registry). Am J Cardiol. 2010;106:329–36.

    Article  PubMed  Google Scholar 

  26. Chieffo A, Foglieni C, Nodari RL, Briguori C, Sangiorgi G, Latib A, Montorfano M, Airoldi F, Michev I, Carlino M, Colombo A, Maseri A. Histopathology of clinical coronary restenosis in drug-eluting versus bare metal stents. Am J Cardiol. 2009;104:1660–7.

    Article  CAS  PubMed  Google Scholar 

  27. Ishida T, Tanaka K. Effects of fibrin and fibrinogen-degradation products on the growth of rabbit aortic smooth muscle cells in culture. Atherosclerosis. 1982;44:161–74.

    Article  CAS  PubMed  Google Scholar 

  28. Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O’Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003;349:1315–23.

    Article  CAS  PubMed  Google Scholar 

  29. 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. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med. 2004;350:221–31.

    Article  CAS  PubMed  Google Scholar 

  30. Palmerini T, Biondi-Zoccai G, Della Riva D, Stettler C, Sangiorgi D, D’Ascenzo F, Kimura T, Briguori C, Sabate M, Kim HS, De Waha A, Kedhi E, Smits PC, Kaiser C, Sardella G, Marullo A, Kirtane AJ, Leon MB, Stone GW. Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis. Lancet. 2012;379:1393–402.

    Article  CAS  PubMed  Google Scholar 

  31. Otsuka F, Vorpahl M, Nakano M, Foerst J, Newell JB, Sakakura K, Kutys R, Ladich E, Finn AV, Kolodgie FD, Virmani R. Pathology of second-generation everolimus-eluting stents versus first-generation sirolimus- and paclitaxel-eluting stents in humans. Circulation. 2014;129:211–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Serruys PW, Onuma Y, Garcia-Garcia HM, Muramatsu T, van Geuns RJ, de Bruyne B, Dudek D, Thuesen L, Smits PC, Chevalier B, McClean D, Koolen J, Windecker S, Whitbourn R, Meredith I, Dorange C, Veldhof S, Hebert KM, Rapoza R, Ormiston JA. Dynamics of vessel wall changes following the implantation of the absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months. Eurointervention. 2014;9:1271–84.

    Article  PubMed  Google Scholar 

  33. Serruys PW, Ormiston JA, Onuma Y, Regar E, Gonzalo N, Garcia-Garcia HM, Nieman K, Bruining N, Dorange C, Miquel-Hebert K, Veldhof S, Webster M, Thuesen L, Dudek D. A bioabsorbable everolimus-eluting coronary stent system (absorb): 2-year outcomes and results from multiple imaging methods. Lancet. 2009;373:897–910.

    Article  CAS  PubMed  Google Scholar 

  34. Finn AV, Nakazawa G, Joner M, Kolodgie FD, Mont EK, Gold HK, Virmani R. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler Thromb Vasc Biol. 2007;27:1500–10.

Download references

Acknowledgments

CVPath Institute Inc. solely provided full support for this work. Dr. Virmani receives research support from Abbott Vascular, BioSensors International, Biotronik, Boston Scientific, Medtronic, MicroPort Medical, OrbusNeich Medical, SINO Medical Technology, and Terumo Corporation; has speaking engagements with Merck; receives honoraria from Abbott Vascular, Boston Scientific, Lutonix, Medtronic, and Terumo Corporation; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr. Nakano has received speaking honorarium from Abbott Vascular, Boston Scientific, and Terumo Corporation. CVPath Institute has research Grants from Abbott Vascular, Biosensors International, Boston Scientific, Cordis/Johnson&Johnson, Medtronic CardioVascular, OrbusNeich Medical, and Terumo Corporation.

Author information

Authors and Affiliations

  1. CVPath Institute, Inc., 19 Firstfield Road, Gaithersburg, MD, 20878, USA

    Masataka Nakano & Renu Virmani

Authors
  1. Masataka Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renu Virmani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Renu Virmani.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakano, M., Virmani, R. Histopathology of vascular response to drug-eluting stents: an insight from human autopsy into daily practice. Cardiovasc Interv and Ther 30, 1–11 (2015). https://doi.org/10.1007/s12928-014-0281-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12928-014-0281-5

Keywords

Search

Navigation