Editorial 633
Drug-eluting stents for drug-eluting stent restenosis: stick with the old or switch to a new one? Sebastian Kufnera and Adnan Kastratia,b,c Coronary Artery Disease 2014, 25:633–635 a
ISA Research Center, Department of Cardiology, German Heart Center Munich, Klinikum rechts der Isar, Department of Cardiology, Technical University Munich and cDZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany b
Percutaneous coronary intervention (PCI) with stent implantation is among the most frequently performed medical procedures worldwide. Despite the high antirestenotic efficacy of currently used interventional techniques, a non-negligible number of patients still present with restenosis. Although successive iterations – from plain balloon angioplasty to bare metal stenting (BMS) to drug-eluting stent (DES) therapy – have seen a progressive decline in the rate of this complication, in-stent restenosis remains a problem commonly encountered in clinical practice. Restenosis after stenting is a distinct pathophysiological process. The dominant mechanism of restenosis after stenting is vascular smooth muscle hyperplasia and extracellular matrix deposition. Yet, there are certain morphological and histological differences in the restenosis after DES versus BMS. Restenosis after DES is more often focal and the neointimal tissue has a higher content of extracellular matrix compared with restenosis after BMS [1–3]. Neoatherosclerosis is observed more often and earlier with DES than with BMS [4]. Advances in intravascular imaging such as optical coherence tomography enable an in-vivo identification of these characteristics (Fig. 1) [5,6]. Randomized trials have clearly shown that DESs are superior to plain balloon angioplasty and brachytherapy for the treatment of BMS restenosis [7–9]. A mechanistic intravascular ultrasound study confirmed a marked reduction in neointimal proliferation seen after use of a DES [9]. DES implantation has become the most frequent type of PCI in patients with coronary artery disease. This is due to the marked reduction in the risk of restenosis as compared with BMS [10]. However, about 5–10% of patients receiving a DES are in need of revascularization of the treated vessel during the first year after PCI [11]. Moreover, owing to the worldwide increase in the use of DESs in complex clinical and lesion subsets [12–14], the absolute number is expected to increase in the years to come. When DES restenosis occurs, it represents a challenging clinical entity in terms of treatment and the corresponding optimal treatment strategy is still a matter of debate [6]. Because of the differences between DES 0954-6928 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Correspondence to Adnan Kastrati, MD, ISA Research Centre, Deutsches Herzzentrum, Technische Universität, Lazarettstrasse 36, 80636 Munich, Germany Tel: + 49 9 1218 4578; fax: + 49 89 1218 4053; e-mail: [email protected] Received 7 August 2014 Revised 10 August 2014 Accepted 11 August 2014
and BMS restenosis, the results generated by studies on treatment of BMS restenosis may not be readily applicable to the DES. Nevertheless, based on the favorable results from the treatment of BMS restenosis [8,9,15,] on the one hand, and the overall inferiority of plain balloon angioplasty as compared with repeat DES implantation in several RCTs, on the other [3,16,17], repeat DES implantation has gained widespread use in the current clinical practice of treatment of DES restenosis. However, it is still unclear whether repeat DES implantation to treat DES restenosis represents the best treatment option [18]. Indeed, treatment of DES restenosis is associated with poorer late outcomes than those obtained after treatment of BMS restenosis [3,11,19]. Different pathophysiological mechanisms have been advocated to explain these findings [20]. DESs are typically composed of three key components: mechanical stent backbone, active drug, and polymer coating. Besides polymer coating causing the problem of delayed vascular healing after DES implantation, the role of specific drug resistance has become a matter of current debate. Although the etiology of restenosis within DESs is multifactorial, some emerging data suggest a contributory role for drug hyporesponsiveness in the restenosis occurring within the DES. There are concerns regarding impaired efficacy of limus-eluting stents in patients with diabetes based on a possible hyporesponsiveness to sirolimus. In particular, hyperglycemia may promote resistance to ‘limus’ drugs at their target receptor mTOR (the mammalian target of rapamycin) and could be an important factor in the development of in-stent restenosis in diabetic patients after sirolimus-eluting stent implantation [21]. In addition, recent observations suggest a contributory role for drug hyporesponsiveness in patients with restenosis occurring within previously implanted sirolimus-eluting stents [19]. There are several studies assessing whether patients with DES restenosis could derive particular benefit from a strategy of treatment based on switching to a different type of DES from that originally used [3,17,22–24]. The switch strategy is based on the intuitively attractive hypothesis that it might overcome drug resistance or specific polymer-related problems. In the nonrandomized RIBS III (Restenosis Intra-Stent: Balloon DOI: 10.1097/MCA.0000000000000171
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
634 Coronary Artery Disease 2014, Vol 25 No 8
Fig. 1
(a)
(b) ∗
∗
Optical coherence tomography (OCT) of a restenotic lesion in a patient who was presented with chest pain 10 years after the implantation of a sirolimus-eluting stent. (a) Subocclusive in-stent restenosis (yellow arrows showing stent struts) with the typical heterogeneous pattern in OCT (white arrows) (b) Imaging after placement of an everolimus-eluting stent showing the two layers of stent struts (yellow arrows showing old stent struts; light blue arrows showing the new stent struts). *Guide wire artifact.
Angioplasty vs. Drug-Eluting Stent) study, including 363 patients with DES restenosis, the main finding was that a hetero-DES approach was associated with better clinical outcomes [17]. The ISAR-DESIRE 2 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis 2) trial randomly allocated 450 patients with in-limus-eluting stent restenosis to undergo repeat stenting with either sirolimus-eluting stent (homoDES) versus paclitaxel-eluting stent (hetero-DES) [3]. Regarding antirestenotic efficacy, there were no differences between the two treatment strategies. However, the equivalent efficacy of both stents was most likely related to a relative failure of the limus-eluting stent, which had clearly outperformed the paclitaxel-eluting in other settings [19,25]. Yet, it is unclear whether it is related to a specific sirolimus hyporesponsiveness at an individual patient level. Therefore, the hypothesis of Nojima and colleagues [26] now reporting on their experience with three different treatment approaches for DES restenosis is undoubtly well justified. The issue of whether a DES eluting the same or a similar type of drug (homo-DES) versus a different type of drug (hetero-DES) should be selected has continued to attract considerable interest [18]. Nojima and colleagues now compared the hetero-DES strategy with either a homo-DES strategy or plain balloon angioplasty. In this study, the homo-DES strategy was defined as the implantation of the same specific DES type as the first one, and hetero-DES strategy included both switching to a different drug or switching to a different stent generation (first-generation DES to second-
generation DES or vice versa). The authors identified diabetes, hemodialysis, and a diffuse restenosis pattern as independent factors associated with an increased risk of recurrence. They concluded that the use of DESs for DES restenosis is superior to balloon angioplasty; however, a hetero-DES strategy did not improve the outcomes compared with the homo-DES strategy. Whereas the findings regarding the correlates of recurrent restenosis and the superiority of DES over plain balloon angioplasty are interesting and in line with previous reports, the study is less helpful for the selection of the DES type to be used. The reason for this is the way they defined the homo-DES and the hetero-DES groups. First, second-generation DESs were present in both the homo-DES and the hetero-DES groups, preventing the ability to assess whether second-generation DESs are overall superior to first-generation DESs in the treatment of DES restenosis. Second, there was no clear separation between the drug classes used for the different DESs due to the low number of patients in the respective groups. This did not enable any conclusion about the value of switching the type of drug during the treatment of restenosis, which remains an interesting topic for future investigations. Drug-coated balloons (DCB) represent a more recent treatment option for patients with DES restenosis. Randomized trials have shown that the clinical results achieved by DCB are comparable with those obtained with repeated DES implantation [16]. This might be seen as an advantage of this treatment option considering the avoidance of an additional metal layer in the coronary vessel. For this reason, DCB deserve inclusion in future
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Drug-eluting stents for drug-eluting stent restenosis Kufner and Kastrati 635
studies assessing treatment options for patients with DES restenosis. Ongoing studies are also evaluating the role of restenotic lesion preparation by cutting balloons in enhancing the effectiveness of local drug delivery (ISARDESIRE 4 ISAR-DESIRE 4, Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-Stent Restenosis 4; NCT0163237). Another technology that awaits investigation in this setting is bioresorbable DES. Future studies should also take advantage of the imaging capacity of optical coherence tomography and its potential to guide the selection of the most appropriate treatment option for the individual patient with in-stent restenosis. Despite the tremendous progress made in the prevention of this complication, restenosis still remains a challenging issue and focus of intensive research in the years to come.
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Acknowledgements Conflicts of interest
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There are no conflicts of interest.
References 1 Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF, et al. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Circulation 1999; 100:1872–1878. 2 Latib A, Mussardo M, Ielasi A, Tarsia G, Godino C, Al-Lamee R, et al. Longterm outcomes after the percutaneous treatment of drug-eluting stent restenosis. JACC Cardiovasc Interv 2011; 4:155–164. 3 Mehilli J, Byrne RA, Tiroch K, Pinieck S, Schulz S, Kufner S, et al. ISARDESIRE 2 Investigators. Randomized trial of paclitaxel- versus sirolimuseluting 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; 55:2710–2716. 4 Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, et al. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol 2011; 57:1314–1322. 5 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. 6 Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol 2014; 63:2659–2673. 7 Dibra A, Kastrati A, Alfonso F, Seyfarth M, Pérez-Vizcayno MJ, Mehilli J, Schömig A. Effectiveness of drug-eluting stents in patients with bare-metal in-stent restenosis: meta-analysis of randomized trials. J Am Coll Cardiol 2007; 49:616–623. 8 Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, et al. ISAR-DESIRE Study Investigators. Sirolimus-eluting stent or paclitaxeleluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial. JAMA 2005; 293:165–171. 9 Alfonso F, Pérez-Vizcayno MJ, Hernandez R, Bethencourt A, Martí V, LópezMínguez JR, et al. RIBS-II Investigators. 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; 47:2152–2160. 10 Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schömig A, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet 2007; 370:937–948.
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Dangas GD, Claessen BE, Caixeta A, Sanidas EA, Mintz GS, Mehran R. Instent restenosis in the drug-eluting stent era. J Am Coll Cardiol 2010; 56:1897–1907. Dibra A, Kastrati A, Mehilli J, Pache J, Schühlen H, von Beckerath N, et al. ISAR-DIABETES Study Investigators. Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients. N Engl J Med 2005; 353:663–670. Stone GW, Kedhi E, Kereiakes DJ, Parise H, Fahy M, Serruys PW, Smits PC. Differential clinical responses to everolimus-eluting and paclitaxel-eluting coronary stents in patients with and without diabetes mellitus. Circulation 2011; 124:893–900. Colombo A, Moses JW, Morice MC, Ludwig J, Holmes DR Jr, Spanos V, et al. Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation 2004; 109:1244–1249. Alfonso F, Pérez-Vizcayno MJ, Hernández R, Bethencourt A, Martí V, LópezMínguez JR, et al. RIBS-II Investigators. 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 sirolimuseluting Stenting) study. J Am Coll Cardiol 2008; 52:1621–1627. Byrne RA, Neumann FJ, Mehilli J, Pinieck S, Wolff B, Tiroch K, et al. ISARDESIRE 3 investigators. 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; 381:461–467. Alfonso F, Pérez-Vizcayno MJ, Dutary J, Zueco J, Cequier A, GarcíaTouchard A, et al. RIBS-III Study Investigators (under the auspices of the Working Group on Interventional Cardiology of the Spanish Society of Cardiology). 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; 5:728–737. Kastrati A, Byrne R. New roads, new ruts: lessons from drug-eluting stent restenosis. JACC Cardiovasc Interv 2011; 4:165–167. Byrne RA, Cassese S, Windisch T, King LA, Joner M, Tada 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. Cassese S, Byrne RA, Tada T, Pinieck S, Joner M, Ibrahim T, et al. Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography. Heart 2014; 100:153–159. Patterson C, Mapera S, Li HH, Madamanchi N, Hilliard E, Lineberger R, et al. Comparative effects of paclitaxel and rapamycin on smooth muscle migration and survival: role of AKT-dependent signaling. Arterioscler Thromb Vasc Biol 2006; 26:1473–1480. Kim YH, Lee BK, Park DW, Park KH, Choi BR, Lee CW, et al. Comparison with conventional therapies of repeated sirolimus-eluting stent implantation for the treatment of drug-eluting coronary stent restenosis. Am J Cardiol 2006; 98:1451–1454. Garg S, Smith K, Torguson R, Okabe T, Slottow TL, Steinberg DH, et al. Treatment of drug-eluting stent restenosis with the same versus different drug-eluting stent. Catheter Cardiovasc Interv 2007; 70:9–14. Kufner S, Byrne RA, de Waha A, Schulz S, Joner M, Laugwitz KL, Kastrati A. Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for InStent Restenosis 2, (ISAR-DESIRE 2) Investigators. Sirolimus-eluting versus paclitaxel-eluting stents in diabetic and non-diabetic patients within sirolimuseluting stent restenosis: results from the ISAR-DESIRE 2 trial. Cardiovasc Revasc Med 2014; 15:69–75. Schömig A, Dibra A, Windecker S, Mehilli J, Suárez de Lezo J, Kaiser C, et al. A meta-analysis of 16 randomized trials of sirolimus-eluting stents versus paclitaxel-eluting stents in patients with coronary artery disease. J Am Coll Cardiol 2007; 50:1373–1380. Nojima Y, Yasuoka Y, Kume K, Adachi H, Hattori S, Matsutera R, et al. Switching types of drug-eluting stents does not prevent repeated in-stent restenosis in patients with coronary drug-eluting stent restenosis. Coron Artery Dis 2014; 25:638–644.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Drug-eluting stents for drug-eluting stent restenosis: stick with the old or switch to a new one? Sebastian Kufnera and Adnan Kastratia,b,c Coronary Artery Disease 2014, 25:633–635 a
ISA Research Center, Department of Cardiology, German Heart Center Munich, Klinikum rechts der Isar, Department of Cardiology, Technical University Munich and cDZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany b
Percutaneous coronary intervention (PCI) with stent implantation is among the most frequently performed medical procedures worldwide. Despite the high antirestenotic efficacy of currently used interventional techniques, a non-negligible number of patients still present with restenosis. Although successive iterations – from plain balloon angioplasty to bare metal stenting (BMS) to drug-eluting stent (DES) therapy – have seen a progressive decline in the rate of this complication, in-stent restenosis remains a problem commonly encountered in clinical practice. Restenosis after stenting is a distinct pathophysiological process. The dominant mechanism of restenosis after stenting is vascular smooth muscle hyperplasia and extracellular matrix deposition. Yet, there are certain morphological and histological differences in the restenosis after DES versus BMS. Restenosis after DES is more often focal and the neointimal tissue has a higher content of extracellular matrix compared with restenosis after BMS [1–3]. Neoatherosclerosis is observed more often and earlier with DES than with BMS [4]. Advances in intravascular imaging such as optical coherence tomography enable an in-vivo identification of these characteristics (Fig. 1) [5,6]. Randomized trials have clearly shown that DESs are superior to plain balloon angioplasty and brachytherapy for the treatment of BMS restenosis [7–9]. A mechanistic intravascular ultrasound study confirmed a marked reduction in neointimal proliferation seen after use of a DES [9]. DES implantation has become the most frequent type of PCI in patients with coronary artery disease. This is due to the marked reduction in the risk of restenosis as compared with BMS [10]. However, about 5–10% of patients receiving a DES are in need of revascularization of the treated vessel during the first year after PCI [11]. Moreover, owing to the worldwide increase in the use of DESs in complex clinical and lesion subsets [12–14], the absolute number is expected to increase in the years to come. When DES restenosis occurs, it represents a challenging clinical entity in terms of treatment and the corresponding optimal treatment strategy is still a matter of debate [6]. Because of the differences between DES 0954-6928 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Correspondence to Adnan Kastrati, MD, ISA Research Centre, Deutsches Herzzentrum, Technische Universität, Lazarettstrasse 36, 80636 Munich, Germany Tel: + 49 9 1218 4578; fax: + 49 89 1218 4053; e-mail: [email protected] Received 7 August 2014 Revised 10 August 2014 Accepted 11 August 2014
and BMS restenosis, the results generated by studies on treatment of BMS restenosis may not be readily applicable to the DES. Nevertheless, based on the favorable results from the treatment of BMS restenosis [8,9,15,] on the one hand, and the overall inferiority of plain balloon angioplasty as compared with repeat DES implantation in several RCTs, on the other [3,16,17], repeat DES implantation has gained widespread use in the current clinical practice of treatment of DES restenosis. However, it is still unclear whether repeat DES implantation to treat DES restenosis represents the best treatment option [18]. Indeed, treatment of DES restenosis is associated with poorer late outcomes than those obtained after treatment of BMS restenosis [3,11,19]. Different pathophysiological mechanisms have been advocated to explain these findings [20]. DESs are typically composed of three key components: mechanical stent backbone, active drug, and polymer coating. Besides polymer coating causing the problem of delayed vascular healing after DES implantation, the role of specific drug resistance has become a matter of current debate. Although the etiology of restenosis within DESs is multifactorial, some emerging data suggest a contributory role for drug hyporesponsiveness in the restenosis occurring within the DES. There are concerns regarding impaired efficacy of limus-eluting stents in patients with diabetes based on a possible hyporesponsiveness to sirolimus. In particular, hyperglycemia may promote resistance to ‘limus’ drugs at their target receptor mTOR (the mammalian target of rapamycin) and could be an important factor in the development of in-stent restenosis in diabetic patients after sirolimus-eluting stent implantation [21]. In addition, recent observations suggest a contributory role for drug hyporesponsiveness in patients with restenosis occurring within previously implanted sirolimus-eluting stents [19]. There are several studies assessing whether patients with DES restenosis could derive particular benefit from a strategy of treatment based on switching to a different type of DES from that originally used [3,17,22–24]. The switch strategy is based on the intuitively attractive hypothesis that it might overcome drug resistance or specific polymer-related problems. In the nonrandomized RIBS III (Restenosis Intra-Stent: Balloon DOI: 10.1097/MCA.0000000000000171
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
634 Coronary Artery Disease 2014, Vol 25 No 8
Fig. 1
(a)
(b) ∗
∗
Optical coherence tomography (OCT) of a restenotic lesion in a patient who was presented with chest pain 10 years after the implantation of a sirolimus-eluting stent. (a) Subocclusive in-stent restenosis (yellow arrows showing stent struts) with the typical heterogeneous pattern in OCT (white arrows) (b) Imaging after placement of an everolimus-eluting stent showing the two layers of stent struts (yellow arrows showing old stent struts; light blue arrows showing the new stent struts). *Guide wire artifact.
Angioplasty vs. Drug-Eluting Stent) study, including 363 patients with DES restenosis, the main finding was that a hetero-DES approach was associated with better clinical outcomes [17]. The ISAR-DESIRE 2 (Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis 2) trial randomly allocated 450 patients with in-limus-eluting stent restenosis to undergo repeat stenting with either sirolimus-eluting stent (homoDES) versus paclitaxel-eluting stent (hetero-DES) [3]. Regarding antirestenotic efficacy, there were no differences between the two treatment strategies. However, the equivalent efficacy of both stents was most likely related to a relative failure of the limus-eluting stent, which had clearly outperformed the paclitaxel-eluting in other settings [19,25]. Yet, it is unclear whether it is related to a specific sirolimus hyporesponsiveness at an individual patient level. Therefore, the hypothesis of Nojima and colleagues [26] now reporting on their experience with three different treatment approaches for DES restenosis is undoubtly well justified. The issue of whether a DES eluting the same or a similar type of drug (homo-DES) versus a different type of drug (hetero-DES) should be selected has continued to attract considerable interest [18]. Nojima and colleagues now compared the hetero-DES strategy with either a homo-DES strategy or plain balloon angioplasty. In this study, the homo-DES strategy was defined as the implantation of the same specific DES type as the first one, and hetero-DES strategy included both switching to a different drug or switching to a different stent generation (first-generation DES to second-
generation DES or vice versa). The authors identified diabetes, hemodialysis, and a diffuse restenosis pattern as independent factors associated with an increased risk of recurrence. They concluded that the use of DESs for DES restenosis is superior to balloon angioplasty; however, a hetero-DES strategy did not improve the outcomes compared with the homo-DES strategy. Whereas the findings regarding the correlates of recurrent restenosis and the superiority of DES over plain balloon angioplasty are interesting and in line with previous reports, the study is less helpful for the selection of the DES type to be used. The reason for this is the way they defined the homo-DES and the hetero-DES groups. First, second-generation DESs were present in both the homo-DES and the hetero-DES groups, preventing the ability to assess whether second-generation DESs are overall superior to first-generation DESs in the treatment of DES restenosis. Second, there was no clear separation between the drug classes used for the different DESs due to the low number of patients in the respective groups. This did not enable any conclusion about the value of switching the type of drug during the treatment of restenosis, which remains an interesting topic for future investigations. Drug-coated balloons (DCB) represent a more recent treatment option for patients with DES restenosis. Randomized trials have shown that the clinical results achieved by DCB are comparable with those obtained with repeated DES implantation [16]. This might be seen as an advantage of this treatment option considering the avoidance of an additional metal layer in the coronary vessel. For this reason, DCB deserve inclusion in future
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Drug-eluting stents for drug-eluting stent restenosis Kufner and Kastrati 635
studies assessing treatment options for patients with DES restenosis. Ongoing studies are also evaluating the role of restenotic lesion preparation by cutting balloons in enhancing the effectiveness of local drug delivery (ISARDESIRE 4 ISAR-DESIRE 4, Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-Stent Restenosis 4; NCT0163237). Another technology that awaits investigation in this setting is bioresorbable DES. Future studies should also take advantage of the imaging capacity of optical coherence tomography and its potential to guide the selection of the most appropriate treatment option for the individual patient with in-stent restenosis. Despite the tremendous progress made in the prevention of this complication, restenosis still remains a challenging issue and focus of intensive research in the years to come.
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Acknowledgements Conflicts of interest
17
There are no conflicts of interest.
References 1 Mehran R, Dangas G, Abizaid AS, Mintz GS, Lansky AJ, Satler LF, et al. Angiographic patterns of in-stent restenosis: classification and implications for long-term outcome. Circulation 1999; 100:1872–1878. 2 Latib A, Mussardo M, Ielasi A, Tarsia G, Godino C, Al-Lamee R, et al. Longterm outcomes after the percutaneous treatment of drug-eluting stent restenosis. JACC Cardiovasc Interv 2011; 4:155–164. 3 Mehilli J, Byrne RA, Tiroch K, Pinieck S, Schulz S, Kufner S, et al. ISARDESIRE 2 Investigators. Randomized trial of paclitaxel- versus sirolimuseluting 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; 55:2710–2716. 4 Nakazawa G, Otsuka F, Nakano M, Vorpahl M, Yazdani SK, Ladich E, et al. The pathology of neoatherosclerosis in human coronary implants bare-metal and drug-eluting stents. J Am Coll Cardiol 2011; 57:1314–1322. 5 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. 6 Alfonso F, Byrne RA, Rivero F, Kastrati A. Current treatment of in-stent restenosis. J Am Coll Cardiol 2014; 63:2659–2673. 7 Dibra A, Kastrati A, Alfonso F, Seyfarth M, Pérez-Vizcayno MJ, Mehilli J, Schömig A. Effectiveness of drug-eluting stents in patients with bare-metal in-stent restenosis: meta-analysis of randomized trials. J Am Coll Cardiol 2007; 49:616–623. 8 Kastrati A, Mehilli J, von Beckerath N, Dibra A, Hausleiter J, Pache J, et al. ISAR-DESIRE Study Investigators. Sirolimus-eluting stent or paclitaxeleluting stent vs balloon angioplasty for prevention of recurrences in patients with coronary in-stent restenosis: a randomized controlled trial. JAMA 2005; 293:165–171. 9 Alfonso F, Pérez-Vizcayno MJ, Hernandez R, Bethencourt A, Martí V, LópezMínguez JR, et al. RIBS-II Investigators. 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; 47:2152–2160. 10 Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schömig A, et al. Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet 2007; 370:937–948.
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