The Drug-Eluting Stent Saga
2009; Lippincott Williams & Wilkins; Volume: 119; Issue: 5 Linguagem: Dinamarquês
10.1161/circulationaha.108.833921
ISSN1524-4539
AutoresStephan Windecker, Peter Jüni,
Tópico(s)Cardiac Imaging and Diagnostics
ResumoHomeCirculationVol. 119, No. 5The Drug-Eluting Stent Saga Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBThe Drug-Eluting Stent Saga Stephan Windecker and Peter Jüni Stephan WindeckerStephan Windecker From the Department of Cardiology and CTU Bern, Bern University Hospital; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. and Peter JüniPeter Jüni From the Department of Cardiology and CTU Bern, Bern University Hospital; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. Originally published10 Feb 2009https://doi.org/10.1161/CIRCULATIONAHA.108.833921Circulation. 2009;119:653–656Drug-eluting stents (DES) represent a breakthrough technology owing to their potent reduction of restenosis, which is a nuisance in the quality of life of affected patients, a rare cause of myocardial infarction (MI), and the principal shortcoming of stents compared with coronary artery bypass surgery. First-generation DES with controlled release of sirolimus or paclitaxel from durable polymers reduce the need of target lesion revascularization by 50 to 70% compared with bare metal stents, requiring treatment of only 8 patients (number needed to treat 6 to 10) to prevent 1 revascularization event.1 The benefit, albeit attenuated, persists in studies without protocol-mandated angiographic follow-up,2 is particularly pronounced in diabetic patients,3 and endures during long-term follow-up extending to 5 years.1 The safety of first-generation DES has been scrutinized in unprecedented depth and comprehensiveness after insinuation of impaired clinical outcome. Even though mortality and MI were found to be similar or even lower with the use of first-generation DES in randomized trials, meta-analyses, and large-scale registries,4 very late stent thrombosis (ie, sudden thrombotic occlusion of the device >1 year after implantation) emerged as a distinct entity complicating their use.5Article p 680Later-generation DES have been developed with the objective to improve clinical outcomes by providing better deliverability and optimized long-term biocompatibility of polymer coatings and by introducing new antiproliferative drugs. One of these new DES is the everolimus-eluting stent (Abbott Vascular, Santa Clara, Calif), recently approved by the US Food and Drug Administration for percutaneous coronary interventions.6,7 The underlying stent platform is the Multilink Vision stent made of L-605 cobalt chromium alloy with an open cell nonlinear link design and the lowest strut thickness (81 μm) currently available with DES. Everolimus is a sirolimus derivative in which the hydroxyl at position C40 of sirolimus has been alkylated with a 2-hydroxyethyl group, resulting in increased solubility in several organic solvents and galenic excipients. Although binding of everolimus to the FKBP 12 domain is 3-fold and immunosuppressive activity in vitro is 2- to 5-fold lower than with sirolimus, oral everolimus proved at least as potent as sirolimus in models of autoimmune disease and heart transplantation. Everolimus is blended into a 6-μm to 8-μm-thick durable polymer at a concentration of ≈100 μg/cm2 stent surface area. The polymer consists of 2 layers, including a thin primer adhesion layer of poly n-butyl methacrylate (PBMA) and a drug reservoir layer of poly vinylidene fluoride co-hexafluoropropylene (PVDF-HFP), which releases ≈80% of the drug within 30 days after implantation.The everolimus-eluting stent has been directly compared with paclitaxel-eluting stents in the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de novo Native Coronary Artery Lesions (SPIRIT) II6 (N=300) and SPIRIT III7 (N=1002) noninferiority trials. The everolimus-eluting stent was found not only noninferior but superior to paclitaxel-eluting stents in terms of late lumen loss, with trends toward reduced restenosis in both trials. Although SPIRIT III had a primary angiographic end point, the sample size of the trial allowed a meaningful assessment of clinical end points including target vessel failure and major adverse cardiac events. As recently reported, the everolimus-eluting stent was found noninferior in terms of target vessel failure at 9 months (7.2% versus 9.0%, difference −1.9%, 95% confidence interval (CI) −5.6% to 1.8%, Pnoninferiority 80% power to detect a relative-risk reduction of ≈40%, as currently observed for the composite of cardiac death or MI for everolimus-eluting stents compared with paclitaxel-eluting stents (Figure) at a 2-sided α of 0.05. Third, is the risk of very late stent thrombosis lower with everolimus-eluting stents than paclitaxel-eluting stents and can thienopyridines be discontinued after 6 months? Although this question remains unresolved for the moment, a collaborative effort with pooling of data from multiple trials with long-term follow-up may allow insights into potential differences between various DES platforms.For the time being, everolimus-eluting stents are superior to paclitaxel-eluting stents not only in terms of angiographic but also in terms of clinical efficacy. The lower rate of target lesion revascularization is robust, maintained throughout 2 years, and in line with the superior reduction in neointimal hyperplasia. If confirmed in future studies, the potential for a reduced risk of early and late MIs, as well as very late stent thrombosis in conjunction with potent restenosis reduction, is intriguing and may meaningfully improve outcomes with drug-eluting stents.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.On request, Abbott Vascular provided summary data of various outcome parameters at 1 and 2 years for SPIRIT II and SPIRIT III so that the meta-analysis provided in this editorial could be performed.DisclosuresDr Windecker is consultant for Abbott, Biosensors, Biotronik, Boston Scientific, Medtronic, and Johnson and Johnson, and he receives lecture fees from Abbott, Biosensors, Biotronik, Boston Scientific, Medtronic, and Johnson and Johnson. Dr Jüni reports no conflicts.FootnotesCorrespondence to Stephan Windecker, MD, Department of Cardiology, Bern University Hospital, 3010 Bern, Switzerland. E-mail [email protected] References 1 Stettler C, Wandel S, Allemann S, Kastrati A, Morice MC, Schomig A, Pfisterer ME, Stone GW, Leon MB, de Lezo JS, Goy JJ, Park SJ, Sabate M, Suttorp MJ, Kelbaek H, Spaulding C, Menichelli M, Vermeersch P, Dirksen MT, Cervinka P, Petronio AS, Nordmann AJ, Diem P, Meier B, Zwahlen M, Reichenbach S, Trelle S, Windecker S, Jüni P. Outcomes associated with drug-eluting and bare-metal stents. Lancet. 2007; 370: 937–948.CrossrefMedlineGoogle Scholar2 Marroquin OC, Selzer F, Mulukutla SR, Williams DO, Vlachos HA, Wilensky RL, Tanguay JF, Holper EM, Abbott JD, Lee JS, Smith C, Anderson WD, Kelsey SF, Kip KE. A comparison of bare-metal and drug-eluting stents for off-label indications. N Engl J Med. 2008; 358: 342–352.CrossrefMedlineGoogle Scholar3 Stettler C, Allemann S, Wandel S, Kastrati A, Morice MC, Schomig A, Pfisterer ME, Stone GW, Leon MB, de Lezo JS, Goy JJ, Park SJ, Sabate M, Suttorp MJ, Kelbaek H, Spaulding C, Menichelli M, Vermeersch P, Dirksen MT, Cervinka P, De Carlo M, Erglis A, Chechi T, Ortolani P, Schalij MJ, Diem P, Meier B, Windecker S, Jüni P. Drug eluting and bare metal stents in people with and without diabetes. BMJ. 2008; 337: a1331.CrossrefMedlineGoogle Scholar4 Windecker S, Jüni P. Safety of drug-eluting stents. Nat Clin Pract Cardiovasc Med. 2008; 5: 316–328.CrossrefMedlineGoogle Scholar5 Windecker S, Meier B. Late coronary stent thrombosis. Circulation. 2007; 116: 1952–1965.LinkGoogle Scholar6 Serruys P, Ruygrok P, Piek JJ, Seth A, Schofer J, Richardt G, Wiemer M, Carrie D, Thuesen L, Boone E, Miguel-Herbert K, Daemen J. A randomized comparison of an everolimus eluting coronary stent with a paclitaxel eluting coronary stent. EuroIntervention. 2006; 2: 286–294.MedlineGoogle Scholar7 Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Mahaffey KW, Cutlip DE, Fitzgerald PJ, Sood P, Su X, Lansky AJ. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease. JAMA. 2008; 299: 1903–1913.CrossrefMedlineGoogle Scholar8 Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Caputo R, Xenopoulos N, Applegate R, Gordon P, White RM, Sudhir K, Cutlip DE, Petersen JL, for the SPIRIT III Investigators. Randomized comparison of everolimus-eluting and paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions (SPIRIT) III trial. Circulation. 2009; 119: 680–686.LinkGoogle Scholar9 Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW. Clinical end points in coronary stent trials. Circulation. 2007; 115: 2344–2351.LinkGoogle Scholar10 Pocock SJ, Lansky AJ, Mehran R, Popma JJ, Fahy MP, Na Y, Dangas G, Moses JW, Pucelikova T, Kandzari DE, Ellis SG, Leon MB, Stone GW. Angiographic surrogate end points in drug-eluting stent trials. J Am Coll Cardiol. 2008; 51: 23–32.CrossrefMedlineGoogle Scholar11 Schomig A, Dibra A, Windecker S, Mehilli J, Suarez de Lezo J, Kaiser C, Park SJ, Goy JJ, Lee JH, Di Lorenzo E, Wu J, Juni P, Pfisterer ME, Meier B, Kastrati A. 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.CrossrefMedlineGoogle Scholar12 Serruys P. The SPIRIT II Study: a clinical evaluation of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with de novo native coronary artery lesions. Paper presented at: Society for Cardiovascular Angiography and Interventions/American College of Cardiology i2 Late Breaking Clinical Trials session, March 31, 2008. Chicago, Ill.Google Scholar13 Topol EJ, Ferguson JJ, Weisman HF, Tcheng JE, Ellis SG, Kleiman NS, Ivanhoe RJ, Wang AL, Miller DP, Anderson KM, Califf RM. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. JAMA. 1997; 278: 479–484.CrossrefMedlineGoogle Scholar14 Mehta SR, Cannon CP, Fox KA, Wallentin L, Boden WE, Spacek R, Widimsky P, McCullough PA, Hunt D, Braunwald E, Yusuf S. Routine vs selective invasive strategies in patients with acute coronary syndromes. JAMA. 2005; 293: 2908–2917.CrossrefMedlineGoogle Scholar15 Joner M, Nakazawa G, Finn AV, Quee SC, Coleman L, Acampado E, Wilson PS, Skorija K, Cheng Q, Xu X, Gold HK, Kolodgie FD, Virmani R. Endothelial cell recovery between comparator polymer-based drug-eluting stents. J Am Coll Cardiol. 2008; 52: 333–342.CrossrefMedlineGoogle Scholar16 Verheye S, Martinet W, Kockx MM, Knaapen MW, Salu K, Timmermans JP, Ellis JT, Kilpatrick DL, De Meyer GR. Selective clearance of macrophages in atherosclerotic plaques by autophagy. J Am Coll Cardiol. 2007; 49: 706–715.CrossrefMedlineGoogle Scholar17 Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans. J Am Coll Cardiol. 2006; 48: 193–202.CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. 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Basavarajaiah S, Naganuma T, Latib A and Colombo A (2013) Can bioabsorbable scaffolds be used in calcified lesions?, Catheterization and Cardiovascular Interventions, 10.1002/ccd.24939, 84:1, (48-52), Online publication date: 1-Jul-2014. Gandhi P and Murthy Z (2012) Investigation of Different Drug Deposition Techniques on Drug Releasing Properties of Cardiovascular Drug Coated Balloons, Industrial & Engineering Chemistry Research, 10.1021/ie3006676, 51:33, (10800-10823), Online publication date: 22-Aug-2012. Raval A, Parikh J and Engineer C (2010) Dexamethasone eluting biodegradable polymeric matrix coated stent for intravascular drug delivery, Chemical Engineering Research and Design, 10.1016/j.cherd.2010.03.007, 88:11, (1479-1484), Online publication date: 1-Nov-2010. Morrison D (2010) Limitations of stints: A good, albeit imperfect, therapy; For a less than perfect world, Catheterization and Cardiovascular Interventions, 10.1002/ccd.22449, 75:3, (343-344), Online publication date: 15-Feb-2010. February 10, 2009Vol 119, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.108.833921PMID: 19204314 Originally publishedFebruary 10, 2009 KeywordsEditorialsrestenosisischemiastentsPDF download Advertisement SubjectsCoronary CirculationImagingRestenosis
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