Article

Contemporary Management of Stent Failure: Part One

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Abstract

The occurrence of in-stent restenosis (ISR) still remains a daunting challenge in the current era, despite advancements in coronary intervention technology. The authors explore the underlying pathophysiology and mechanisms behind ISR, and describe how the use of different diagnostic tools helps to best elucidate these. They propose a simplistic algorithm to manage ISR, including a focus on how treatment strategies should be selected and a description of the contemporary technologies available. This article aims to provide a comprehensive outline of ISR that can be translated into evidence-based routine clinical practice, with the aim of providing the best outcomes for patients.

Disclosure:PO is a speaker and proctor for Philips and Abbott Vascular. All other authors have no conflicts of interest to declare.

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Accepted:

Correspondence Details:Peter O’Kane, Dorset Heart Centre, Royal Bournemouth Hospital, Castle Lane East, Bournemouth BH7 7DW, UK. E: Peter.O’Kane@rbch.nhs.uk

Copyright Statement:

The copyright in this work belongs to Radcliffe Medical Media. Only articles clearly marked with the CC BY-NC logo are published with the Creative Commons by Attribution Licence. The CC BY-NC option was not available for Radcliffe journals before 1 January 2019. Articles marked ‘Open Access’ but not marked ‘CC BY-NC’ are made freely accessible at the time of publication but are subject to standard copyright law regarding reproduction and distribution. Permission is required for reuse of this content.

The reduction in risk of cardiac death offered by revascularisation in patients with moderate to large amount of stress-induced myocardial ischaemia has driven advancements in percutaneous coronary intervention (PCI) technology over the last four decades.1 However, despite significant progress in the techniques, equipment and pharmacotherapy, target lesion failure remains the Achilles heel of a PCI approach in patients with coronary heart disease.

The advent of the bare metal stent (BMS) introduced a major shift and promised improved outcomes over percutaneous balloon angioplasty (POBA). The BMS prevented the elastic recoil and constrictive remodelling that was seen frequently with POBA (32–55% incidence).2,3 However, it was soon realised that the benefits of deploying a metallic scaffold were still accompanied with a significant (17–41%) incidence of restenosis within the stented segment.4–7

Further research and development in stent technology led to the emergence of drug-eluting stents (DES), with successive generations produced on platforms with different anti-proliferative drugs, advanced polymers, improved stent cell design and thinner metallic struts. This promised to solve the spectre of in-stent restenosis (ISR) completely by preventing early tissue formation after stent deployment. These improvements have certainly led to superior results with reduced target lesion failure and target lesion revascularisation, MI and stent thrombosis when compared with BMS or the earlier generation of DES.8,9

However, despite these major developments, the incidence of DES ISR remains between 5 and 10% and is an independent predictor of mortality, thereby making it the foremost adversary of an interventional cardiologist in the modern era.10,11 This review highlights a simplified approach for identifying the mechanism of ISR and describe strategies to select devices for therapy and illustrate this with clinical cases (Figures 1–6).

Definition of In-stent Restenosis

ISR is angiographically defined as >50% reduction in luminal area within the stent or in the adjacent native vessel (5 mm of the proximal or distal stent edge).12 The clinical definition, however, includes the angiographic appearance and the presence of one of the following:

  • clinical symptoms suggestive of coronary heart disease;
  • ECG changes suggestive of underlying coronary ischaemia;
  • significant limitation in coronary flow as measured by a positive haemodynamic assessment such as fractional flow reserve or instantaneous wave-free ratio (iFR);
  • minimum cross-sectional area of <4 mm2 (6 mm2 for left main stem) using intravascular ultrasound; or
  • a reduction of >70% in luminal area, even in the absence of symptoms.13

Mehran’s classification system was developed for morphological classification of BMS ISR, but it has also shown prognostic value in DES ISR as well.14,15 As per the classification, the ISR is described to be focal, diffuse, proliferative or occlusive, and it helps in predicting the rate of revascularisation (19%, 35%, 50% and 98%, respectively).14

Chronic Total Occlusion of Left Anterior Descending Artery Secondary to Stent Failure

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Stent Failure Secondary to Probable Stent Fracture in Mid-LAD Stents

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Stent Failure Secondary to Undersized Stent

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Anterior ST-elevation MI Secondary to a Very Late Stent Thrombosis of Left Anterior Descending Artery&lt;br /&gt;&#10;Stent Failure

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Treatment of Severe In-stent Restenosis in Left Main Stem, Left Anterior Descending Artery and Left Circumflex Artery

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Stent Failure Secondary to Severe Calcification and Neo-atherosclerosis in Left Circumflex Artery

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Factors Influencing the Development of In-stent Restenosis

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Simplified Approach to Stent Failure Cases

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Risk Factors for Developing In-stent Restenosis

Several factors play important roles in the development of ISR in BMS and DES (Figure 7). Diabetes is perhaps the most well-established patient risk factor for ISR, particularly with BMS – the rate of BMS ISR may be as high as 30–50%.16–19 There are various lesion characteristics that lead to non-uniform drug distribution and thus contribute to a higher incidence of ISR.

The presence of moderate or severe calcification is perhaps one of the most challenging aspects of PCI in contemporary practice. There is clear evidence that the degree of lesion calcification directly affects stent expansion. In many large-scale clinical studies, calcification has been shown to be proportionally linked to stent failure, with increased rates of target lesion failure, target vessel revascularisation, MI and death in patients with the most lesion calcification.20,21 Advancing a stent through a calcified tortuous vessel may lead to disruption of polymer and/or drug on the surface, which can reduce the efficacy of even the best-designed DES.

PCI of long lesions (>20 mm) and small calibre vessels (<3 mm and especially those <2.5 mm) carries a much higher risk of ISR and such characteristics are often seen when treating chronic total occlusion. The risk of ISR doubles if the length of the stented segment is >35 mm compared to <20 mm.12,22,23 The relation of vessel diameter to ISR was reported in the Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial, where vessel size <3 mm was related to a significantly higher incidence of ISR.24 Bifurcation lesions, especially those treated with a double stent (the main vessel and side branch technique), have a higher incidence of stent failure, particularly in the side branch.25

Pathophysiology of In-stent Restenosis

It has been observed that ISR secondary to BMS versus DES has different characteristics, with important ones being time lag from stent implantation to presentation, morphology of the ISR itself and response to treatment.26,27 BMS ISR presents early (typically 6–8 months) as compared to DES ISR (typically after 2 years) which often has a delayed presentation.28

The initial inflammatory process ensues soon after the stent is implanted, and is characterised by deposition of platelets and fibrin, as well as adhesions of circulating neutrophils and macrophages. Over several weeks these cells are replaced by chronic inflammatory cells, which include macrophages and giant cells. Simultaneously, this vascular injury from the stent struts in the intima induces the initial stimuli for vascular smooth muscle cell proliferation and activation. As a result, the vascular smooth muscle cells migrate from the tunica media, and the myofibroblasts migrate from the tunica adventitia into the tunica intima, forming an extracellular matrix. This is proven by the systemic surge in the levels of the inflammatory markers post PCI and also by the presence of inflammatory cells in the plaque.29 These processes culminate in the formation of a neointimal layer over the stented segment, with its luminal side covered by the endothelial cells.22,30

DES ISR is characterised by delayed healing of the vessel wall secondary to stent components such as the durable polymer. Though the durable polymer facilitates drug delivery, it also results in a chronic non-specific inflammatory process (especially the durable polymer on first generation DES), which results in incomplete neo-endothelialisation, and occasionally can cause a specific hypersensitivity reaction.31 This led to the development of biodegradable polymers, but recent data have suggested similar safety and efficacy of biodegradable polymer DES compared to second generation durable polymer DES.32

The above pathogenic processes lead to different time of onset and morphological characteristics. While BMS ISR peaks around 3–6 months after stent implantation and has a diffuse pattern of neointima formation, DES ISR has a predominantly focal pattern, with onset after 6–9 months and increasing up to 2 years after implantation.31,33

Neo-atherosclerosis

When describing the pathophysiology of ISR, it is important to understand the process of neo-atherosclerosis. As with native vessel, the atherosclerotic process can affect neointima as well. This occurs due to incomplete endothelialisation, which is seen more commonly in DES as compared to BMS, primarily due to the elution of the drug itself.34,35 This results in uptake of circulating lipids and formation of plaque, which is thin-capped and occurs earlier in DES than BMS (2 years versus 6 years, respectively).34 There are several independent risk factors that lead to neo-atherosclerosis: young age, longer duration after stent implantation, sirolimus or paclitaxel-eluting stents, smoking, chronic kidney disease and LDL-cholesterol >3.9 mmol/l.34

ISR was earlier considered to be a benign clinical pathology, but can can present as acute coronary syndrome (ACS).36,37 Magalhaes et al. found that the incidence of ACS in the patient presenting with DES-ISR (second-generation DES) requiring target vessel revasculariation was 66.7%, and MI was 5.2%.38 This occurs as a result of an acceleration of the neo-atherosclerotic process, which culminates in plaque rupture and thrombus formation, possibly manifesting as late stent thrombosis.39 It is also important to remember that stable patients with ISR have a favourable prognosis, and should be assessed with contemporary validated technologies such as pressure wire before undertaking PCI.40,41

Diagnosis and Evaluation of In-stent Restenosis

Selective coronary angiography is the initial diagnostic tool to diagnose and assess ISR, despite its limited resolution. Although modern features of fluoroscopic equipment, such as stent enhancement, permit diagnosis of an underexpanded stent, it is rare for coronary angiography alone to provide sufficient insight into the mechanism of stent failure. Intra-coronary imaging tools such as intravascular ultrasound and optical coherence tomography (OCT) are now recommended for PCI for stent failure, since either imaging technique allows detailed assessment of the native vessel and stented segment to provide precise mechanistic information (Figure 8).42 Such factors that might easily be identified are stent undersizing, underdeployment or underexpansion, geographical miss of the lesion and stent fracture.43,44 Intra-coronary imaging also assists the visualisation of neo-intimal hyperplasia, neo-atherosclerosis, edge stenosis, underlying calcification and provides clear instruction on what devices are necessary to prepare the lesion and then accurately size and expand the stent.45 Evidence supports this approach. For example, intravascular ultrasound-guided revascularisation has been shown to provide better clinical and angiographic results,46,47 with a 1 mm2 increase in minimal stent area found to be associated with a 20% decrease in BMS ISR.27,48

OCT has a better axial resolution (15 μm), which helps to morphologically differentiate between the homogenous high signal tissue band of BMS (constituted by neointimal hyperplasia which is rich in vascular smooth muscle cells) and the heterogeneous, focal and layered tissue band of DES (rich in proteoglycan and fibrin content).27,49

Also, before considering therapy on angiographic diagnosed ISR in stable patients, it is important to assess whether the lesion is causing ischaemia and guide therapy using adjunctive and validated technology such as pressure wire (Figure 8).40,41 It has been previously shown that coronary angiography alone correlates poorly with the functional significance of moderate ISR lesions.41,50 With the advent of the iFR and SyncVision technology, it is now possible to simultaneously assess the functional significance of the lesion, measure the length of the expected stented segment and predict the post revascularistion iFR, all of which can be performed without inducing hyperaemia.51

Treatment of In-stent Restenosis

Bare Metal Stent In-stent Restenosis

Over the years, several advancements have been made in the treatment of ISR with an initial focus on BMS-ISR, which had a high incidence rate.4–6 Identification of the mechanism of ISR is critical to the understanding of how best to deal with the lesion. For instance, an undersized stent with minimal intra-luminal material may best be optimised by just balloon dilatation (Figure 8). More complex mechanisms of ISR such as severe neointimal hyperplasia or neo-atherosclerosis may require debulking strategies, using tools such as scoring balloons or atherectomy (Figure 2). There have been many studies comparing alterative PCI strategies for treatment of ISR (Table 1).

Two trials studying the role of rotational atherectomy in treatment of BMS ISR produced conflicting results. Rotational atherectomy had significantly lower target lesion failure rates in the Rotational Atherectomy Versus Balloon Angioplasty for Diffuse In-stent Restenosis (ROSTER) trial, while POBA had significantly lower restenosis in the Angioplasty Versus Rotational Atherectomy for Treatment of Diffuse In-stent Restenosis Trial (ARTIST).52,53

The use of excimer laser atherectomy confers several advantages, such as the ability to modify plaque behind stent struts, decreased potential risk of distal emboli and lower risk of stent fracture or entrapment.54–56 These advantages have translated into superior outcomes such as greater acute luminal gain when treating complex DES ISR, as recently reported by Ichimoto et al.57 In chronically occluded ISR or where there is an inability to cross the lesion with disease-modifying devices, excimer laser atherectomy is the better option.

Once the existing stent has been adequately optimised, the next decision is how to prevent future ISR due to vessel injury and provide a long-term durable solution. The use of a drug-eluting balloon (DEB) potentially confers certain advantages over a DES. These include homogenous distribution of the drug in the vessel wall (especially if the original stent was suboptimally expanded), absence of polymer leading to reduction in the chronic inflammatory process, and reduced number of layers of the stent struts.58 The clinical and angiographic advantage of paclitaxel-eluting balloon (PEB) compared with POBA and PES in the treatment of BMS ISR was shown in the Treatment of In-stent Restenosis by Paclitaxel Coated PTCA Balloons (PACCOCATH ISR) I and II and Paclitaxel-Eluting PTCA-balloon catheter in Coronary Artery Disease (PEPCAD) II trials, respectively.59–61 The role of PEB in treatment of BMS ISR was further established when it demonstrated comparable results against the everolimus-eluting stent (EES) in the Restenosis Intra-Stent of Bare Metal Stents (RIBS) V and Treatment of In-Stent restenosis (TIS) trials.62,63

The use of DES in the treatment of BMS ISR was evaluated and firmly confirmed by the Sirolimus-Eluting Stent for In-Stent Restenosis (SISR) and the TAXUS Paclitaxel-Eluting Coronary Stent in the Treatment of In-Stent Restenosis (TAXUS V ISR) trials, both revealing lower rates of binary restenosis and better clinical outcomes with DES compared to complex brachytherapy.64,65 Similarly, when DES was compared to POBA for treating BMS ISR, it showed superior results in the ISAR-DESIRE and RIBS II trial.66,67

Drug-eluting Stent In-stent Restenosis

DES ISR is associated with worse outcomes than BMS ISR, and this has led to the development of different treatment strategies using DES or PEB.68,69 Lesion preparation in the treatment of -limus DES ISR was studied in the Intracoronary Stenting and Angiographic Results: Drug-Eluting Stents for In-Stent Restenosis (ISAR-DESIRE) 4 trial, where the use of a scoring balloon before DEB resulted in a significantly lower percentage of diameter stenosis and restenosis rate compared to POBA.70 This difference is contributed by better precision, power (15–25 times higher than POBA), uniform expansion and safety (lower dissection and perforation rates) of the angiosculpt scoring balloon compared to POBA.71–73

Given that most contemporary cases of ISR are in DES and not BMS, the option of simply re-treating the lesion with another DES is usually not ideal. As described above, DEB offers several advantages, and these have been established in the treatment of DES ISR as well. PEB was found to be better or equally effective in treating DES ISR when compared to POBA or PES, as studied in the PEPCAD-DES and PEPCAD China ISR and ISAR-DESIRE 3 trials, respectively.74–76 Similarly, Naganuma et al. reported no difference in the target vessel revascularisation and MACE endpoints, when bifurcation BMS/DES ISR was treated using either EES or PEB.77 When PEB was compared to EES in the treatment of DES ISR, conflicting results were revealed by the Drug-Eluting Balloon for In-Stent Restenosis (DARE) trial and the recently published 3-year outcome data from the RIBS IV trial.78,79 Thus there is a sufficient body of evidence supporting the use of DEB in the treatment of DES ISR where clinically suited and indicated.

Treating DES ISR secondary to stent undersizing, edge dissection or stent fracture is best treated using another DES. The role of similar DES (homo) or different DES (hetero) has been evaluated to understand if a similar or different anti-proliferative drug offers any advantage. This has been studied in the ISAR-DESIRE 2, New Generation Drug Eluting Stent for In-stent Restenosis of Drug Eluting Stent (RESTENT-ISR) and RIBS III trials.80–82 While the ISAR-DESIRE 2 and RESTENT-ISR revealed no significant difference between the use of homo or hetero stents, RIBS III found significantly better clinical and angiographic outcomes in the hetero-DES group.

An alternative concept to the repeated use of DES when a DEB alone is considered inadequate has been to consider bioresorbable devices. This could potentially offer the opportunity of treating ISR without implanting long-term multiple layers of stents (known as the ‘onion skin’). Absorb (Abbott Vascular) had been the most widely used bioresorbable vascular scaffold since first-in-man studies in simple de novo lesions in 2006.83

In recently published literature, rates of target lesion failure rates at 12 months of 9.1–12.2% have been reported with bioresorbable vascular scaffolds in the treatment of BMS/DES ISR.84,85 Although used by some operators in ISR cases, the relative large strut thickness (160 μm), footprint and need for near-perfect lesion preparation significantly restricted use in stent failure for the majority of BVS implanters. Absorb was removed from the market in 2017 after several studies pointed to increased scaffold thrombosis rates compared to DES and failure to match target lesion failure/target vessel revascularisation rates within the first 3 years while the device resorbed.

Conclusion

Stent failure through in-stent restenosis remains an occurrence that interventional cardiologists will face on a routine basis. Utilisation of diagnostic tools, such as pressure wire assessment and intracoronary imaging, provide better insights compared with angiography alone, and permit more focussed therapies to treat these lesions. The repeat revascularisation often requires adjunctive devices to optimise the outcome and provide long-term durable result. Although data are available to currently support the PCI strategies that we have discussed in this paper, further research will be necessary to distinguish which are the superior PCI techniques within this heterogeneous patient cohort.

References

  1. Petretta M, Acampa W, Daniele S, et al. Long-term survival benefit of coronary revascularization in patients undergoing stress myocardial perfusion imaging. Circ J 2016;80:485–93.
    Crossref | PubMed
  2. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med 1994;331:496–501.
    Crossref | PubMed
  3. Holmes DR, Vlietstra RE, Smith HC, et al. Restenosis after percutaneous transluminal coronary angioplasty (PTCA): a report from the PTCA Registry of the National Heart, Lung, and Blood Institute. Am J Cardiol 1984;53:77C–81.
    Crossref | PubMed
  4. Fishman RF, Kuntz RE, Carrozza JP, et al. Long-term results of directional coronary atherectomy: predictors of restenosis. J Am Coll Cardiol 1992;20:1101–10.
    Crossref | PubMed
  5. Le Feuvre C, Bonan R, Lespérance J, et al. Predictive factors of restenosis after multivessel percutaneous transluminal coronary angioplasty. Am J Cardiol 1994;73:840–4.
    Crossref | PubMed
  6. Bakhai A, Booth J, Delahunty N, et al. The SV Stent study: a prospective, multicentre, angiographic evaluation of the BiodivYsio phosphorylcholine coated small vessel stent in small coronary vessels. Int J Cardiol 2005;102:95–102.
    Crossref | PubMed
  7. Agostoni P, Valgimigli M, Biondi-Zoccai GL, et al. Clinical effectiveness of bare-metal stenting compared with balloon angioplasty in total coronary occlusions: insights from a systematic overview of randomized trials in light of the drug-eluting stent era. Am Heart J 2006;151:682–9.
    Crossref | PubMed
  8. Kedhi E, Joesoef KS, McFadden E, et al. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet 2010;375:201–9.
    Crossref | PubMed
  9. Harjai KJ, Kondareddy S, Pinkosky B, et al. Everolimus-eluting stents versus sirolimus- or paclitaxel-eluting stents: two-year results from the Guthrie Health Off-Label Stent (GHOST) Registry. J Interv Cardiol 2013;26:153–62.
    Crossref | PubMed
  10. 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.
    Crossref | PubMed
  11. Taniwaki M, Stefanini GG, Silber S, et al. 4-year clinical outcomes and predictors of repeat revascularisation 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;63:1617–25.
    Crossref | PubMed
  12. Mehran R, Mintz GS, Popma JJ, et al. Mechanisms and results of balloon angioplasty for the treatment of in-stent restenosis. Am J Cardiol 1996;78:618–22.
    Crossref | PubMed
  13. Dangas GD, Claessen BE, Caixeta A, et al. In-stent restenosis in the drug-eluting stent era. J Am Coll Cardiol 2010;56:1897–907.
    Crossref | PubMed
  14. 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.
    PubMed
  15. 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.
    Crossref | PubMed
  16. Kastrati A, Schömig A, Elezi S, et al. Predictive factors of restenosis after coronary stent placement. J Am Coll Cardiol 1997;30:1428–36.
    Crossref | PubMed
  17. Jukema JW, Verschuren JJ, Ahmed TA, Quax PH. Restenosis after PCI. Part 1: pathophysiology and risk factors. Nat Rev Cardiol 2011;9:53–62.
    Crossref | PubMed
  18. Elezi S, Kastrati A, Pache J, et al. Diabetes mellitus and the clinical and angiographic outcome after coronary stent placement. J Am Coll Cardiol 1998;32:1866–73.
    Crossref | PubMed
  19. Kastrati A, Dibra A, Mehilli J, et al. Predictive factors of restenosis after coronary implantation of sirolimus- or paclitaxel-eluting stents. Circulation 2006;113:2293–300.
    Crossref | PubMed
  20. Vavuranakis M, Toutouzas K, Stefanadis C, et al. Stent Deployment in Calcified Lesions: Can we Overcome Calcific Restraint With High-Pressure Balloon Inflations? Catheter Cardiovasc Interv 2001;52:164–72.
    PubMed
  21. Généreux P, Madhavan MV, Mintz GS, et al. Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes: pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularisation and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterisation and Urgent Intervention Triage Strategy) trials. J Am Coll Cardiol 2014;63:1845–54.
    Crossref | PubMed
  22. Kim MS, Dean LS. In-stent restenosis. Cardiovas Ther 2011;29:190–8.
    Crossref | PubMed
  23. Kobayashi Y, De Gregorio J, Kobayashi N, et al. Stented segment length as an independent predictor of restenosis. J Am Coll Cardiol 1999;34:651–9.
    Crossref | PubMed
  24. Stone GW, Parise H, Witzenbichler B, et al. Selection criteria for drug-eluting versus bare-metal stents and the impact of routine angiographic follow-up: 2-year insights from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. J Am Coll Cardiol 2010;56:1597–604.
    Crossref | PubMed
  25. Behan MW, Holm NR, de Belder AJ, et al. Coronary bifurcation lesions treated with simple or complex stenting: 5-year survival from patient-level pooled analysis of the Nordic Bifurcation Study and the British Bifurcation Coronary Study. Eur Heart J 2016;37:1923–8.
    Crossref | PubMed
  26. Stone GW, Ellis SG, Cannon L, et al. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial. JAMA 2005;294:1215–23.
    Crossref | PubMed
  27. Byrne RA, Joner M, Tada T, Kastrati A. Restenosis in bare metal and drug-eluting stents: distinct mechanistic insights from histopathology and optical intravascular imaging. Minerva Cardioangiol 2012;60:473–89.
    PubMed
  28. Collet CA, Costa JR, Abizaid A, et al. Assessing the temporal course of neointimal hyperplasia formation after different generations of drug-eluting stents. JACC Cardiovasc Interv 2011;4:1067–74.
    Crossref | PubMed
  29. Piek JJ, van der Wal AC, Meuwissen M, et al. Plaque inflammation in restenotic coronary lesions of patients with stable or unstable angina. J Am Coll Cardiol 2000;35:963–7.
    Crossref | PubMed
  30. Scott NA. Restenosis following implantation of bare metal coronary stents: pathophysiology and pathways involved in the vascular response to injury. Adv Drug Deliv Rev 2006;58:358–76.
    Crossref | PubMed
  31. Farooq V, Räber L, Gogas BD, Serruys PW. In-stent restenosis. In: Eeckhout E, Serruys PW, Wijns W, et al. (eds). The PCR-EAPCI Textbook: Percutaneous Interventional Cardiovascular Medicine. 1st ed. Toulouse, France: Europa, 2012.
  32. El-Hayek G, Bangalore S, Dominguez A, et al. Meta-analysis of randomized clinical trials comparing biodegradable polymer drug-eluting stent to second-generation durable polymer drug-eluting stents. JACC Cardiovasc Interv 2017;10:462–73.
    Crossref | PubMed
  33. Cosgrave J, Melzi G, Biondi-Zoccai GG, et al. Drug-eluting stent restenosis: the pattern predicts the outcome. J Am Coll Cardiol 2006;47:2399–404.
    Crossref | PubMed
  34. Nakazawa G, Otsuka F, Nakano M, et al. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol 2011;57:1314–22.
    Crossref | PubMed
  35. Yonetsu T, Kato K, Kim SJ, et al. Predictors for neoatherosclerosis. Circ Cardiovasc Imaging 2012;5:660–6.
    Crossref | PubMed
  36. Cassese S, Byrne RA, Tada T, et al. Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography. Heart 2014;100:153–9.
    Crossref | PubMed
  37. 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.
    Crossref | PubMed
  38. Magalhaes MA, Minha S, Chen F, et al. Clinical presentation and outcomes of coronary in-stent restenosis across 3-stent generations. Circ Cardiovasc Interv 2014;7:768–76.
    Crossref | PubMed
  39. Nicolais C, Lakhter V, Virk HU, et al. Therapeutic options for in-stent restenosis. Curr Cardiol Rep 2018;20:7.
    Crossref | PubMed
  40. Nam C-W, Rha SW, Koo B-K, et al. Usefulness of coronary pressure measurement for functional evaluation of drug-eluting stent restenosis. Am J Cardiol 2011;107:1783–6.
    Crossref | PubMed
  41. Lopez-Palop R, Pinar E, Lozano I, et al. Utility of the fractional flow reserve in the evaluation of angiographically moderate in-stent restenosis. Eur Heart J 2004;25:2040–7.
    Crossref | PubMed
  42. 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.
    Crossref | PubMed
  43. Fujii K, Mintz GS, Kobayashi Y, et al. Contribution of stent underexpansion to recurrence after sirolimus-eluting stent implantation for in-stent restenosis. Circulation 2004;109:1085–8.
    Crossref | PubMed
  44. Gutiérrez-Chico JL, Alegría-Barrero E, Teijeiro-Mestre R, et al. Optical coherence tomography: from research to practice. Eur Heart J Cardiovasc Imaging 2012;13:370–84.
    Crossref | PubMed
  45. García-García HM, Shen Z, Piazza N. Study of restenosis in drug eluting stents: new insights from greyscale intravascular ultrasound and virtual histology. EuroIntervention 2009;5(Suppl D):D84–92.
    PubMed
  46. Zhang Y, Farooq V, García-García HM, et al. Comparison of intravascular ultrasound versus angiography-guided drug-eluting stent implantation: a meta-analysis of one randomised trial and ten observational studies involving 19,619 patients. EuroIntervention 2012;8:855–65.
    Crossref | PubMed
  47. Ahn JM, Kang SJ, Yoon SH, et al. Meta-analysis of outcomes after intravascular ultrasound-guided versus angiography-guided drug-eluting stent implantation in 26,503 patients enrolled in three randomized trials and 14 observational studies. Am J Cardiol 2014;113:1338–47.
    Crossref | PubMed
  48. Kasaoka S, Tobis JM, Akiyama T, et al. Angiographic and intravascular ultrasound predictors of in-stent restenosis. J Am Coll Cardiol 1998;32:1630–5.
    Crossref | PubMed
  49. Kang SJ, Mintz GS, Akasaka T, et al. Optical coherence tomographic analysis of in-stent neoatherosclerosis after drug-eluting stent implantation. Circulation 2011;123:2954–63.
    Crossref | PubMed
  50. Yamashita J, Tanaka N, Fujita H, et al. Usefulness of functional assessment in the treatment of patients with moderate angiographic paclitaxel-eluting stent restenosis. Circ J 2013;77:1180–5.
    Crossref | PubMed
  51. Davies JE, et al. Coronary artery physiological stenosis mapping: application of pressure wire technology to measure stenosis significance, length, and predict the outcome of intervention. Presented at EuroPCR, Paris, France, 21 May 2014.
  52. Sharma SK, Kini A, Mehran R, et al. Randomized trial of Rotational Atherectomy Versus Balloon Angioplasty for Diffuse In-stent Restenosis (ROSTER). Am Heart J 2004;147:16–22.
    Crossref | PubMed
  53. vom Dahl J, Dietz U, Haager P et al. Rotational atherectomy does not reduce recurrent in-stent restenosis. Results of the Angioplasty Versus Rotational Atherectomy for Treatment of Diffuse In-stent Restenosis Trial (ARTIST). Circulation 2002;105:583–8.
    PubMed
  54. Dahm JB, Kuon E. High-energy eccentric excimer laser angioplasty for debulking diffuse in-stent restenosis leads to better acute- and 6-month follow-up results. J Invasive Cardiol 2000;12:335–42.
    PubMed
  55. Nishino M, Mori N, Takiuchi S, et al. Indications and outcomes of excimer laser coronary atherectomy: efficacy and safety for thrombotic lesions – the ULTRAMAN registry. J Cardiol 2017;69:314–9.
    Crossref | PubMed
  56. Mehran R, Mintz GS, Satler LF, et al. Treatment of in-stent restenosis with excimer laser coronary angioplasty: mechanisms and results compared with PTCA alone. Circulation 1997;96:2183–9.
    PubMed
  57. Ichimoto E, Kadohira T, Nakayama T, De Gregorio J. Long-term clinical outcomes after treatment with excimer laser coronary atherectomy for in-stent restenosis of drug-eluting stent. Int Heart J 2018;59:14–20.
    Crossref | PubMed
  58. Chin K. In-stent restenosis: the gold standard has changed. EuroIntervention 2011;7(Suppl K):K43–6.
    Crossref | PubMed
  59. 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;355:2113–24.
    Crossref | PubMed
  60. 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.
    Crossref | PubMed
  61. 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.
    Crossref | PubMed
  62. Alfonso F, Pérez-Vizcayno MJ, Cárdenas 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.
    Crossref | PubMed
  63. Pleva L, Kukla P, Kusnierova P, et al. Comparison of the efficacy of paclitaxel-eluting balloon catheters and everolimus-eluting stents in the treatment of coronary in-stent restenosis: the Treatment of In-Stent Restenosis study. Circ Cardiovasc Interv 2016;9:e003316.
    Crossref | PubMed
  64. Holmes DR, 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.
    Crossref | PubMed
  65. 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.
    Crossref | PubMed
  66. 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.
    Crossref | PubMed
  67. 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;47:2152–60.
    Crossref | PubMed
  68. Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol 2014;63:2659–73.
    Crossref | PubMed
  69. Latib A, Mussardo M, Lelasi A, et al. Long-term outcomes after the percutaneous treatment of drug-eluting stent restenosis. JACC Cardiovasc Interv 2011;4:155–64.
    Crossref | PubMed
  70. 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.
    Crossref | PubMed
  71. de Ribamar Costa J Jr, Mintz GS, Carlier SG, et al. Nonrandomized comparison of coronary stenting under intravascular ultrasound guidance of direct stenting without predilation versus conventional predilation with a semi-compliant balloon versus predilation with a new scoring balloon. Am J Cardiol 2007;100:812–7.
    Crossref | PubMed
  72. Takano M, Yamamoto M, Murakami et al. Optical coherence tomography after new scoring balloon angioplasty for in-stent restenosis and de novo coronary lesions. Int J Cardiol 2010;141:e51–3.
    Crossref | PubMed
  73. Weisz G, Metzger DC, Liberman HA, et al. A provisional strategy for treating true bifurcation lesions employing a scoring balloon for the side branch. Catheter Cardiovasc Interv 2013;82:352–9.
    Crossref | PubMed
  74. 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.
    Crossref | PubMed
  75. Xu B, Gao R, Wang J, et al. A prospective, multicenter, randomized trial of paclitaxel-coated balloon versus paclitaxel-eluting stent for the treatment of drug-eluting stent in-stent restenosis: results from the PEPCAD China ISR trial. JACC Cardiovasc Interv 2014;7:204–11.
    Crossref | PubMed
  76. 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.
    Crossref | PubMed
  77. Naganuma T, Latib A, Costopoulos C, et al. Drug-eluting balloon versus second-generation drug-eluting stent for the treatment of restenotic lesions involving coronary bifurcations. EuroIntervention 2016;11:989–95.
    Crossref | PubMed
  78. Baan J, Claessen BE, Dijk KB, et al. A randomized comparison of paclitaxel-eluting balloon versus everolimus-eluting stent for the treatment of any in-stent restenosis: the DARE trial. JACC Cardiovasc Interv 2018;11:275–83.
    Crossref | PubMed
  79. Alfonso F, Pérez-Vizcayno MJ, Cuesta J, et al. 3-year clinical follow-up of the RIBS IV clinical trial: a prospective randomized study of drug-eluting balloons versus everolimus-eluting stents in patients with in-stent restenosis in coronary arteries previously treated with drug-eluting stents. JACC Cardiovasc Interv 2018;11:981–91.
    Crossref | PubMed
  80. 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.
    Crossref | PubMed
  81. Hong SJ, Ahn CM, Kim BK, et al. Prospective randomized comparison of clinical and angiographic outcomes between everolimus-eluting vs zotarolimus-eluting stents for treatment of coronary restenosis in drug-eluting stents: intravascular ultrasound volumetric analysis (RESTENT-ISR Trial). Eur Heart J 2016;37:3409–18.
    Crossref | PubMed
  82. Alfonso F, Pérez-Vizcayno MJ, Dutary J, et al. Implantation of a drug-eluting stent with a different drug (switch strategy) in patients with drug-eluting stent restenosis: results from a prospective multicenter study (RIBS III [Restenosis Intra-Stent: Balloon Angioplasty Versus Drug-Eluting Stent]). JACC Cardiovasc Interv 2012;5:728–37.
    Crossref | PubMed
  83. Ormiston JA, Serruys PW, Regar E, et al. A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet 2008;371:899–907.
    Crossref | PubMed
  84. Jamshidi P, Nyffenegger T, Sabti Z, et al. A novel approach to treat in-stent restenosis: 6- and 12-month results using the everolimus-eluting bioresorbable vascular scaffold. EuroIntervention 2016;11:1479–86.
    Crossref | PubMed
  85. Moscarella E, Lelasi 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.
    Crossref | PubMed