Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Intracoronary stent restenosis

Thomas Levin, MD
Donald Cutlip, MD
Section Editor
Stephan Windecker, MD
Deputy Editor
Gordon M Saperia, MD, FACC


Although intracoronary stent restenosis (ISR) is much less common with the use of drug-eluting stents (DES) than with bare metal stents (BMS), the number of stents being implanted in interventional practice means that the treatment of ISR remains an important clinical challenge.


After a successful procedure, coronary stents can fail to maintain vessel patency due to either restenosis or stent thrombosis. Restenosis is a gradual re-narrowing of the stented segment that occurs mostly between 3 to 12 months after stent placement. It usually presents as recurrent angina, but can present as acute myocardial infarction in approximately 10 percent of patients. It can usually be managed by repeat percutaneous revascularization.

In contrast, stent thrombosis is an abrupt thrombotic occlusion of a previously widely patent stent. It is a catastrophic complication that presents as sudden death or large myocardial infarction in most patients. Despite successful repeat revascularization, the six-month mortality is high. (See "Coronary artery stent thrombosis: Clinical presentation and management" and "Coronary artery stent thrombosis: Incidence and risk factors".)

In this topic, intracoronary stent restenosis (ISR) and in-stent restenosis refer to the same issue.

The following are widely agreed upon definitions related to ISR (table 1) [1]:


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Oct 20, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Dangas GD, Claessen BE, Caixeta A, et al. In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol 2010; 56:1897.
  2. Cutlip DE, Chauhan MS, Baim DS, et al. Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials. J Am Coll Cardiol 2002; 40:2082.
  3. Cutlip DE, Chhabra AG, Baim DS, et al. Beyond restenosis: five-year clinical outcomes from second-generation coronary stent trials. Circulation 2004; 110:1226.
  4. Kimura T, Morimoto T, Nakagawa Y, et al. Very late stent thrombosis and late target lesion revascularization after sirolimus-eluting stent implantation: five-year outcome of the j-Cypher Registry. Circulation 2012; 125:584.
  5. Räber L, Wohlwend L, Wigger M, et al. Five-year clinical and angiographic outcomes of a randomized comparison of sirolimus-eluting and paclitaxel-eluting stents: results of the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization LATE trial. Circulation 2011; 123:2819.
  6. Piccolo R, Stefanini GG, Franzone A, et al. Safety and efficacy of resolute zotarolimus-eluting stents compared with everolimus-eluting stents: a meta-analysis. Circ Cardiovasc Interv 2015; 8.
  7. Hoffmann R, Mintz GS, Dussaillant GR, et al. Patterns and mechanisms of in-stent restenosis. A serial intravascular ultrasound study. Circulation 1996; 94:1247.
  8. Kearney M, Pieczek A, Haley L, et al. Histopathology of in-stent restenosis in patients with peripheral artery disease. Circulation 1997; 95:1998.
  9. Kornowski R, Hong MK, Tio FO, et al. In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 1998; 31:224.
  10. Komatsu R, Ueda M, Naruko T, et al. Neointimal tissue response at sites of coronary stenting in humans: macroscopic, histological, and immunohistochemical analyses. Circulation 1998; 98:224.
  11. Farb A, Sangiorgi G, Carter AJ, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 1999; 99:44.
  12. Chung IM, Gold HK, Schwartz SM, et al. Enhanced extracellular matrix accumulation in restenosis of coronary arteries after stent deployment. J Am Coll Cardiol 2002; 40:2072.
  13. Kimura T, Yokoi H, Nakagawa Y, et al. Three-year follow-up after implantation of metallic coronary-artery stents. N Engl J Med 1996; 334:561.
  14. Asakura M, Ueda Y, Nanto S, et al. Remodeling of in-stent neointima, which became thinner and transparent over 3 years: serial angiographic and angioscopic follow-up. Circulation 1998; 97:2003.
  15. Kuroda N, Kobayashi Y, Nameki M, et al. Intimal hyperplasia regression from 6 to 12 months after stenting. Am J Cardiol 2002; 89:869.
  16. 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.
  17. Hoffmann R, Mintz GS. Coronary in-stent restenosis - predictors, treatment and prevention. Eur Heart J 2000; 21:1739.
  18. Kastrati A, Schömig A, Elezi S, et al. Predictive factors of restenosis after coronary stent placement. J Am Coll Cardiol 1997; 30:1428.
  19. Goldberg SL, Loussararian A, De Gregorio J, et al. Predictors of diffuse and aggressive intra-stent restenosis. J Am Coll Cardiol 2001; 37:1019.
  20. Mercado N, Boersma E, Wijns W, et al. Clinical and quantitative coronary angiographic predictors of coronary restenosis: a comparative analysis from the balloon-to-stent era. J Am Coll Cardiol 2001; 38:645.
  21. Kobayashi Y, De Gregorio J, Kobayashi N, et al. Stented segment length as an independent predictor of restenosis. J Am Coll Cardiol 1999; 34:651.
  22. Lemos PA, Hoye A, Goedhart D, et al. Clinical, angiographic, and procedural predictors of angiographic restenosis after sirolimus-eluting stent implantation in complex patients: an evaluation from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) study. Circulation 2004; 109:1366.
  23. Prati F, Di Mario C, Moussa I, et al. In-stent neointimal proliferation correlates with the amount of residual plaque burden outside the stent: an intravascular ultrasound study. Circulation 1999; 99:1011.
  24. Hoffmann R, Mintz GS, Mehran R, et al. Intravascular ultrasound predictors of angiographic restenosis in lesions treated with Palmaz-Schatz stents. J Am Coll Cardiol 1998; 31:43.
  25. Serruys PW, Kay IP, Disco C, et al. Periprocedural quantitative coronary angiography after Palmaz-Schatz stent implantation predicts the restenosis rate at six months: results of a meta-analysis of the BElgian NEtherlands Stent study (BENESTENT) I, BENESTENT II Pilot, BENESTENT II and MUSIC trials. Multicenter Ultrasound Stent In Coronaries. J Am Coll Cardiol 1999; 34:1067.
  26. Gyöngyösi M, Yang P, Khorsand A, Glogar D. Longitudinal straightening effect of stents is an additional predictor for major adverse cardiac events. Austrian Wiktor Stent Study Group and European Paragon Stent Investigators. J Am Coll Cardiol 2000; 35:1580.
  27. Singh M, Gersh BJ, McClelland RL, et al. Clinical and angiographic predictors of restenosis after percutaneous coronary intervention: insights from the Prevention of Restenosis With Tranilast and Its Outcomes (PRESTO) trial. Circulation 2004; 109:2727.
  28. Mauri L, O'Malley AJ, Cutlip DE, et al. Effects of stent length and lesion length on coronary restenosis. Am J Cardiol 2004; 93:1340.
  29. de Feyter PJ, Kay P, Disco C, Serruys PW. Reference chart derived from post-stent-implantation intravascular ultrasound predictors of 6-month expected restenosis on quantitative coronary angiography. Circulation 1999; 100:1777.
  30. Mauri L, Orav EJ, O'Malley AJ, et al. Relationship of late loss in lumen diameter to coronary restenosis in sirolimus-eluting stents. Circulation 2005; 111:321.
  31. Mauri L, Orav EJ, Kuntz RE. Late loss in lumen diameter and binary restenosis for drug-eluting stent comparison. Circulation 2005; 111:3435.
  32. Mauri L, Orav EJ, Candia SC, et al. Robustness of late lumen loss in discriminating drug-eluting stents across variable observational and randomized trials. Circulation 2005; 112:2833.
  33. Ellis SG, Vandormael MG, Cowley MJ, et al. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Multivessel Angioplasty Prognosis Study Group. Circulation 1990; 82:1193.
  34. Kastrati A, Schömig A, Elezi S, et al. Prognostic value of the modified american college of Cardiology/American heart association stenosis morphology classification for long-term angiographic and clinical outcome after coronary stent placement. Circulation 1999; 100:1285.
  35. Cohen DJ, Doucet M, Cutlip DE, et al. Impact of smoking on clinical and angiographic restenosis after percutaneous coronary intervention: another smoker's paradox? Circulation 2001; 104:773.
  36. Hasdai D, Garratt KN, Grill DE, et al. Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization. N Engl J Med 1997; 336:755.
  37. Violaris AG, Thury A, Regar E, et al. Influence of a history of smoking on short term (six month) clinical and angiographic outcome after successful coronary angioplasty. Heart 2000; 84:299.
  38. Kastrati A, Mehilli J, Dirschinger J, et al. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO) trial. Circulation 2001; 103:2816.
  39. Pache J, Kastrati A, Mehilli J, et al. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO-2) trial. J Am Coll Cardiol 2003; 41:1283.
  40. Yoshitomi Y, Kojima S, Yano M, et al. Does stent design affect probability of restenosis? A randomized trial comparing Multilink stents with GFX stents. Am Heart J 2001; 142:445.
  41. Castagna MT, Mintz GS, Leiboff BO, et al. The contribution of "mechanical" problems to in-stent restenosis: An intravascular ultrasonographic analysis of 1090 consecutive in-stent restenosis lesions. Am Heart J 2001; 142:970.
  42. Kastrati A, Schömig A, Elezi S, et al. Interlesion dependence of the risk for restenosis in patients with coronary stent placement in in multiple lesions. Circulation 1998; 97:2396.
  43. Kastrati A, Dibra A, Mehilli J, et al. Predictive factors of restenosis after coronary implantation of sirolimus- or paclitaxel-eluting stents. Circulation 2006; 113:2293.
  44. Taniwaki M, Stefanini GG, Silber S, et al. 4-year clinical outcomes and predictors of repeat revascularization in patients treated with new-generation drug-eluting stents: a report from the RESOLUTE All-Comers trial (A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention). J Am Coll Cardiol 2014; 63:1617.
  45. Chen MS, John JM, Chew DP, et al. Bare metal stent restenosis is not a benign clinical entity. Am Heart J 2006; 151:1260.
  46. Bossi I, Klersy C, Black AJ, et al. In-stent restenosis: long-term outcome and predictors of subsequent target lesion revascularization after repeat balloon angioplasty. J Am Coll Cardiol 2000; 35:1569.
  47. Walters DL, Harding SA, Walsh CR, et al. Acute coronary syndrome is a common clinical presentation of in-stent restenosis. Am J Cardiol 2002; 89:491.
  48. Mishkel GJ, Moore AL, Markwell S, et al. Long-term outcomes after management of restenosis or thrombosis of drug-eluting stents. J Am Coll Cardiol 2007; 49:181.
  49. Fineschi M, Gori T, Pierli C, et al. Symptomatic failure after sirolimus-eluting stent implantation: a rare but challenging condition. Can J Cardiol 2007; 23:139.
  50. 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.
  51. Alfonso F, Augé JM, Zueco J, et al. Long-term results (three to five years) of the Restenosis Intrastent: Balloon angioplasty versus elective Stenting (RIBS) randomized study. J Am Coll Cardiol 2005; 46:756.
  52. Mehran R, Dangas G, Abizaid A, et al. Treatment of focal in-stent restenosis with balloon angioplasty alone versus stenting: Short- and long-term results. Am Heart J 2001; 141:610.
  53. Sousa JE, Costa MA, Abizaid A, et al. Sirolimus-eluting stent for the treatment of in-stent restenosis: a quantitative coronary angiography and three-dimensional intravascular ultrasound study. Circulation 2003; 107:24.
  54. Degertekin M, Regar E, Tanabe K, et al. Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience. J Am Coll Cardiol 2003; 41:184.
  55. Tanabe K, Serruys PW, Grube E, et al. TAXUS III Trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation 2003; 107:559.
  56. Neumann FJ, Desmet W, Grube E, et al. Effectiveness and safety of sirolimus-eluting stents in the treatment of restenosis after coronary stent placement. Circulation 2005; 111:2107.
  57. 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.
  58. Alfonso F, Pérez-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.
  59. Alfonso F, Pérez-Vizcayno MJ, Hernández R, et al. Long-term clinical benefit of sirolimus-eluting stents in patients with in-stent restenosis results of the RIBS-II (Restenosis Intra-stent: Balloon angioplasty vs. elective sirolimus-eluting Stenting) study. J Am Coll Cardiol 2008; 52:1621.
  60. Habara S, Kadota K, Shimada T, et al. Late Restenosis After Paclitaxel-Coated Balloon Angioplasty Occurs in Patients With Drug-Eluting Stent Restenosis. J Am Coll Cardiol 2015; 66:14.
  61. Garg S, Smith K, Torguson R, et al. Treatment of drug-eluting stent restenosis with the same versus different drug-eluting stent. Catheter Cardiovasc Interv 2007; 70:9.
  62. Abe M, Kimura T, Morimoto T, et al. Sirolimus-eluting stent versus balloon angioplasty for sirolimus-eluting stent restenosis: Insights from the j-Cypher Registry. Circulation 2010; 122:42.
  63. 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.
  64. 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.
  65. Scheller B, Hehrlein C, Bocksch W, et al. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med 2006; 355:2113.
  66. 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.
  67. 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.
  68. Ellis SG, O'Shaughnessy CD, Martin SL, et al. Two-year clinical outcomes after paclitaxel-eluting stent or brachytherapy treatment for bare metal stent restenosis: the TAXUS V ISR trial. Eur Heart J 2008; 29:1625.
  69. 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.
  70. Authors/Task Force members, Windecker S, Kolh P, 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.
  71. Dibra A, Kastrati A, Alfonso F, et al. Effectiveness of drug-eluting stents in patients with bare-metal in-stent restenosis: meta-analysis of randomized trials. J Am Coll Cardiol 2007; 49:616.