In-Stent Restenosis

  • Roisin Colleran
  • Robert A. ByrneEmail author


Restenosis is an arterial wall healing response to mechanical injury at the site of a previously treated coronary segment. In-stent restenosis (ISR) is an angiographic diagnosis, defined as recurrent diameter stenosis >50% within a stent or at its edges (5 mm segments proximal and distal to the stent). It is the most common cause of stent failure and the most common reason for target lesion revascularization (TLR). Moreover, its treatment is challenging owing to a relatively high rate of recurrence at follow-up.


In-stent restenosis Drug-coated balloon Drug-eluting stent Bare metal stent Neointimal hyperplasia Neoatherosclerosis Scoring balloon Cutting balloon 


  1. 1.
    Mehran R, Dangas G, Abizaid AS, et al. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Circulation. 1999;100:1872–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Solinas E, Dangas G, Kirtane AJ, et al. Angiographic patterns of drug-eluting stent restenosis and one-year outcomes after treatment with repeated percutaneous coronary intervention. Am J Cardiol. 2008;102:311–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Alfonso F, Cequier A, Angel J, et al. Value of the American College of Cardiology/American Heart Association angiographic classification of coronary lesion morphology in patients with in-stent restenosis. Insights from the Restenosis Intra-stent Balloon angioplasty versus elective Stenting (RIBS) randomized trial. Am Heart J. 2006;151:681.e1–9.CrossRefGoogle Scholar
  4. 4.
    Cassese S, Byrne RA, Tada T, et al. Incidence and predictors of restenosis after coronary stenting in 10004 patients with surveillance angiography. Heart. 2014;100:153–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Byrne RA, Serruys PW, Baumbach A, et al. Report of a European Society of Cardiology-European Association of Percutaneous Cardiovascular Interventions task force on the evaluation of coronary stents in Europe: executive summary. Eur Heart J. 2015;36:2608–20.CrossRefPubMedGoogle Scholar
  6. 6.
    Cassese S, Byrne RA, Schulz S, et al. Prognostic role of restenosis in 10 004 patients undergoing routine control angiography after coronary stenting. Eur Heart J. 2015;36:94–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL. Bare metal stent restenosis is not a benign clinical entity. Am Heart J. 2006;151:1260–4.CrossRefPubMedGoogle Scholar
  8. 8.
    Byrne RA, Cassese S, Windisch T, et al. Differential relative efficacy between drug-eluting stents in patients with bare metal and drug-eluting stent restenosis; evidence in support of drug resistance: insights from the ISAR-DESIRE and ISAR-DESIRE 2 trials. EuroIntervention. 2013;9:797–802.CrossRefPubMedGoogle Scholar
  9. 9.
    Otsuka F, Byrne RA, Yahagi K, et al. Neoatherosclerosis: overview of histopathologic findings and implications for intravascular imaging assessment. Eur Heart J. 2015;36:2147–59.CrossRefPubMedGoogle Scholar
  10. 10.
    Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35:2541–619.CrossRefPubMedGoogle Scholar
  11. 11.
    Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol. 2014;63:2659–73.CrossRefPubMedGoogle Scholar
  12. 12.
    Siontis GC, Stefanini GG, Mavridis D, et al. Percutaneous coronary interventional strategies for treatment of in-stent restenosis: a network meta-analysis. Lancet. 2015;386:655–64.CrossRefPubMedGoogle Scholar
  13. 13.
    Alfonso F, Zueco J, Cequier A, et al. A randomized comparison of repeat stenting with balloon angioplasty in patients with in-stent restenosis. J Am Coll Cardiol. 2003;42:796–805.CrossRefPubMedGoogle Scholar
  14. 14.
    Mehilli J, Byrne RA, Tiroch K, et al. Randomized trial of paclitaxel- versus sirolimus-eluting stents for treatment of coronary restenosis in sirolimus-eluting stents: the ISAR-DESIRE 2 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis 2) study. J Am Coll Cardiol. 2010;55:2710–6.CrossRefPubMedGoogle Scholar
  15. 15.
    Kastrati A, Mehilli J, von Beckerath N, et al. Sirolimus-eluting stent or paclitaxel-eluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial. JAMA. 2005;293:165–71.CrossRefPubMedGoogle Scholar
  16. 16.
    Alfonso F, Perez-Vizcayno MJ, Hernandez R, et al. A randomized comparison of sirolimus-eluting stent with balloon angioplasty in patients with in-stent restenosis: results of the Restenosis Intrastent: Balloon Angioplasty Versus Elective Sirolimus-Eluting Stenting (RIBS-II) trial. J Am Coll Cardiol. 2006;47:2152–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Byrne RA, Joner M, Alfonso F, Kastrati A. Drug-coated balloon therapy in coronary and peripheral artery disease. Nat Rev Cardiol. 2014;11:13–23.CrossRefPubMedGoogle Scholar
  18. 18.
    Scheller B, Clever YP, Kelsch B, et al. Long-term follow-up after treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. JACC Cardiovasc Interv. 2012;5:323–30.CrossRefPubMedGoogle Scholar
  19. 19.
    Scheller B, Hehrlein C, Bocksch W, et al. Two year follow-up after treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. Clin Res Cardiol. 2008;97:773–81.CrossRefPubMedGoogle Scholar
  20. 20.
    Rittger H, Brachmann J, Sinha AM, et al. A randomized, multicenter, single-blinded trial comparing paclitaxel-coated balloon angioplasty with plain balloon angioplasty in drug-eluting stent restenosis: the PEPCAD-DES study. J Am Coll Cardiol. 2012;59:1377–82.CrossRefPubMedGoogle Scholar
  21. 21.
    Rittger H, Waliszewski M, Brachmann J, et al. Long-term outcomes after treatment with a paclitaxel-coated balloon versus balloon angioplasty: insights from the PEPCAD-DES study (treatment of drug-eluting stent [DES] in-stent restenosis with SeQuent please paclitaxel-coated percutaneous transluminal coronary angioplasty [PTCA] catheter). JACC Cardiovasc Interv. 2015;8:1695–700.CrossRefPubMedGoogle Scholar
  22. 22.
    Habara S, Mitsudo K, Kadota K, et al. Effectiveness of paclitaxel-eluting balloon catheter in patients with sirolimus-eluting stent restenosis. JACC Cardiovasc Interv. 2011;4:149–54.CrossRefPubMedGoogle Scholar
  23. 23.
    Habara S, Iwabuchi M, Inoue N, et al. A multicenter randomized comparison of paclitaxel-coated balloon catheter with conventional balloon angioplasty in patients with bare-metal stent restenosis and drug-eluting stent restenosis. Am Heart J. 2013;166:527–533 e2.CrossRefPubMedGoogle Scholar
  24. 24.
    Unverdorben M, Vallbracht C, Cremers B, et al. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation. 2009;119:2986–94.CrossRefPubMedGoogle Scholar
  25. 25.
    Unverdorben M, Vallbracht C, Cremers B, et al. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis: the three-year results of the PEPCAD II ISR study. EuroIntervention. 2015;11:926–34.CrossRefPubMedGoogle Scholar
  26. 26.
    Alfonso F, Perez-Vizcayno MJ, Cardenas A, et al. A randomized comparison of drug-eluting balloon versus everolimus-eluting stent in patients with bare-metal stent-in-stent restenosis: the RIBS V Clinical Trial (Restenosis Intra-stent of Bare Metal Stents: paclitaxel-eluting balloon vs. everolimus-eluting stent). J Am Coll Cardiol. 2014;63:1378–86.CrossRefPubMedGoogle Scholar
  27. 27.
    Alfonso F, Perez-Vizcayno MJ, Garcia Del Blanco B, et al. Long-term results of everolimus-eluting stents versus drug-eluting balloons in patients with bare-metal in-stent restenosis: 3-year follow-up of the RIBS V clinical trial. JACC Cardiovasc Interv. 2016;9:1246–55.CrossRefPubMedGoogle Scholar
  28. 28.
    Byrne RA, Neumann FJ, Mehilli J, et al. Paclitaxel-eluting balloons, paclitaxel-eluting stents, and balloon angioplasty in patients with restenosis after implantation of a drug-eluting stent (ISAR-DESIRE 3): a randomised, open-label trial. Lancet. 2013;381:461–7.CrossRefPubMedGoogle Scholar
  29. 29.
    Kufner S, Cassese S, Valeskini M, et al. Long-term efficacy and safety of paclitaxel-eluting balloon for the treatment of drug-eluting stent restenosis: 3-year results of a randomized controlled trial. JACC Cardiovasc Interv. 2015;8:877–84.CrossRefPubMedGoogle Scholar
  30. 30.
    Giacoppo D, Gargiulo G, Aruta P, Capranzano P, Tamburino C, Capodanno D. Treatment strategies for coronary in-stent restenosis: systematic review and hierarchical Bayesian network meta-analysis of 24 randomised trials and 4880 patients. BMJ. 2015;351:h5392.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Lee JM, Park J, Kang J, et al. Comparison among drug-eluting balloon, drug-eluting stent, and plain balloon angioplasty for the treatment of in-stent restenosis: a network meta-analysis of 11 randomized, controlled trials. JACC Cardiovasc Interv. 2015;8:382–94.CrossRefPubMedGoogle Scholar
  32. 32.
    Kufner S, Joner M, Schneider S, et al. Neointimal modification with scoring balloon and efficacy of drug-coated balloon therapy in patients with restenosis in drug-eluting coronary stents: a randomized controlled trial. JACC Cardiovasc Interv. 2017;10:1332–40.CrossRefPubMedGoogle Scholar
  33. 33.
    Moscarella E, Ielasi A, Granata F, et al. Long-term clinical outcomes after bioresorbable vascular scaffold implantation for the treatment of coronary in-stent restenosis: a multicenter Italian experience. Circ Cardiovasc Interv. 2016;9:e003148.CrossRefPubMedGoogle Scholar
  34. 34.
    Cassese S, Byrne RA, Ndrepepa G, et al. Everolimus-eluting bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a meta-analysis of randomised controlled trials. Lancet. 2016;387:537–44.CrossRefPubMedGoogle Scholar
  35. 35.
    Stone GW, Ellis SG, O’Shaughnessy CD, et al. Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the TAXUS V ISR randomized trial. JAMA. 2006;295:1253–63.CrossRefPubMedGoogle Scholar
  36. 36.
    Holmes DR Jr, Teirstein P, Satler L, et al. Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the SISR randomized trial. JAMA. 2006;295:1264–73.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Deutsches Herzzentrum München, Technische Universität MünchenMunichGermany
  2. 2.DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceMunichGermany

Personalised recommendations