Bringing Reality to Drug-Eluting Stents
2004; Lippincott Williams & Wilkins; Volume: 109; Issue: 2 Linguagem: Inglês
10.1161/01.cir.0000113457.41084.82
ISSN1524-4539
Autores Tópico(s)Cardiac Valve Diseases and Treatments
ResumoHomeCirculationVol. 109, No. 2Bringing Reality to Drug-Eluting Stents Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBBringing Reality to Drug-Eluting Stents David P. Faxon David P. FaxonDavid P. Faxon From the Section of Cardiology, Department of Medicine, University of Chicago, Chicago, Ill. Originally published20 Jan 2004https://doi.org/10.1161/01.CIR.0000113457.41084.82Circulation. 2004;109:140–142"Nothing ever becomes real till it is experienced"— —John Keats (1795–1821), letter to George and Georgiana Keats, March 19, 1819TThe introduction of drug-eluting stents has unquestionably been one of the most important advances in interventional cardiology during the past decade. The impact has already been profound, despite the release of the first drug-eluting stent, the Cypher stent (Cordis Corp), in the United States earlier this year. Practitioners are now using these devices for a wide variety of clinical and anatomic situations, many of which have not been specifically studied. Many have expressed concerns about the widespread use of these devices in real practice situations because clinical experience might be significantly different from that reported in the randomized clinical trials that led to the devices' approval.See p 190The principal advantage of drug-eluting stents has been the substantial reduction in the incidence of in-stent restenosis. Until recently, the clinical experience has been largely confined to the sirolimus-coated Bx Velocity stent (Cypher stent). Sirolimus (rapamycin) is a macrolite antibiotic discovered on Easter Island.1 The agent is now recognized to activate the kinase target of rapamycin (TOR), which subsequently inhibits cyclin-induced transition from G0 to G1 cell cycle, thus preventing cell division. It also has potent antiinflammatory effects. The initial randomized clinical trial, RAVEL (RAndomized study with the sirolimus-eluting Bx VELocity balloon-expandable stent), evaluated 238 patients with de novo single lesions.2 The restenosis rate at 6 months (>50% stenosis) was an astounding 0% in the sirolimus-eluting stent (SES) group, compared with 26% in the bare metal stent group. Subsequently, the larger SIRIUS trial (multicenter randomized double-blind study of the SIRolImUS-coated Bx Velocity stent in the treatment of patients with de novo coronary artery lesions) studied 1058 patients, including patients with more complex disease.3 This pivotal trial demonstrated that SES reduced target vessel failure from 21% to 8.9%. Benefit was shown for higher-risk subgroups, such as those with long lesions, small vessels, or diabetes. The subsequent E-SIRIUS (the European randomized trial) (n=352)4 and C-SIRIUS (the Canadian randomized trial) (n=100)5 used a similar protocol and also demonstrated benefit in patients with even longer lesions and smaller vessels. The combined study (NEW-SIRIUS) reported a 5.1% in-lesion restenosis rate. These reports led to the approval of SES in the United States and Europe, and to date, >250 000 stents have been implanted.Clinicians have embraced the concept of drug-eluting stents, particularly with the recently reported results from the Treatment of de novo coronary disease using a single paclitAXel-elUting Stent IV (TAXUS IV) study, in which the drug paclitaxel was used. In this multicenter randomized trial, 1314 patients were randomized to a paclitaxel-eluting stent or a bare metal stent, with a reduction in restenosis from 26.6% with bare metal stents to 7.9% for the TAXUS stent.6 The US Food and Drug Administration (FDA) panel has recently recommended approval, and the device should be available in the United States shortly. A growing number of randomized trials are currently ongoing, evaluating a variety of pharmacological agents directed toward inhibition of cell cycle and/or inflammation.7–8 It is extremely likely that we will have a number of drug-eluting stents available in the near future. At present, the results of randomized clinical trials are sufficiently convincing for us to be certain that drug-eluting stents have found a place in the armamentarium of the interventional cardiologist. The consistent results of sirolimus and paclitaxel drug-eluting stents are remarkable and have led many to suggest that all patients who require stenting should receive these devices. The only major constraint to doing so at the present time is cost.9–11 With the approval of additional devices in the future, cost is likely to go down. Although there is no doubt that the results of these trials are impressive, it is critical to realize that randomized clinical trials rarely mimic clinical practice. The pivotal SIRIUS trial included only patients with single-lesion intervention on lesions in vessels between 2.5 and 3.5 mm in diameter and from 5 to 30 mm in length. No patients with acute myocardial infarction, severe unstable angina (Braunwald class III or IV), or chronic renal failure were included. Lesions in saphenous vein grafts, bifurcation lesions, total occlusions, and in-stent restenotic lesions were also excluded from the study. Thus, many of the clinical and anatomic features that commonly occur in most interventional practices were not reflected in this clinical trial because of these and other exclusions. The National Heart, Lung, and Blood Institute (NHLBI) has sponsored a comprehensive registry that has been monitoring the progress of angioplasty since 1977. The most current registry, the Dynamic Registry, involves 26 clinical centers. All patients undergoing percutaneous coronary intervention (PCI) at each center are included in this registry, and 3 separate waves of ≈2000 patients have been studied over the past 6 years. In a recent report of waves 1 and 2, these and other exclusionary features were present in at least 50% of the patients undergoing contemporary PCI12 (Table). This is also true for the most current wave of 2141 patients collected between October 2001 and March 2002 (K. Detre, MD, PhD, unpublished data, 2003). Although exclusion from randomized trials leads to a more homogenous study group, it also frequently excludes those at the highest risk for complications and those who are least likely to show benefit. This is an extremely common and potentially serious problem with many randomized trials. Comparison of SIRIUS and the Research and Dynamic RegistriesSIRIUS3Research13Dynamic Registry12Excluded in SIRIUS: in-stent restenosis, SVG lesion, nonstented lesions, multivessel PCI, ostial lesions, thrombus-containing lesion, calcified lesions, and ejection fraction 290 occurrences of subacute stent thrombosis (SAT) have been reported, and >60 patients have died. Although this is cause for concern, it is important to note that there have been >250 000 stents placed, leading to an overall rate of subacute stent thrombosis of ≈1%. This incidence is within the expected range of SAT for bare metal stents. The randomized trials also did not see any excess rate of SAT, and the Research Registry has not reported an increased incidence. However, it is not certain that all events have been reported to the FDA, and the details of the individual patients have not been fully analyzed to determine if procedural, patient, or device factors were responsible. Clearly, a better reporting system, or preferably, a national database for new devices with careful prospective collection of data should be established. This would allow rapid identification of problems and offer the ability to clearly understand the nature of the problems and factors responsible for them. In addition, it would allow careful monitoring of practitioners' use of these devices in real-world patients. Although the Research Registry, the ongoing Wisdom Registry, and the E-SIRIUS Registry are helpful, they are not designed to collect information on all patients whether they had a drug-eluting stent or not.20–21 Inclusion of all consecutive patients allows a better understanding of who does and who does not get the device. In addition, the quality of the data in this type of voluntary registry is unknown. Isn't it time to seriously consider instituting such a system to collect real-world experiences? National organizations such as the American College of Cardiology have set up a national database, and the NHLBI is funding the continuation of the Dynamic Registry. This will help, but a mandatory FDA requirement for such a registry, run by the NHLBI, for all new devices would greatly improve our understanding and use of these new treatments. Technology is advancing at such a rapid pace, particularly in the field of interventional cardiology, that the need for such a system is greater than at any time in the past. The time to make this happen is now.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.FootnotesCorrespondence to David P. Faxon, MD, Chief, Section of Cardiology, The University of Chicago, 5841 South Maryland Ave, MC 6080, Chicago, IL 60637. E-mail [email protected]References1 Marx SO, Marks AR. Bench to bedside: the development of rapamycin and its application to stent restenosis. 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"Real world" evaluation of slow-release, polymer-based, paclitaxel-eluting TAXUS stents in native coronary arteries: the WISDOM international registry. Circulation. 2003; 108 (suppl IV): IV-534. Abstract.Google Scholar21 Guagliumi G, Sousa E, Urban P, et al. Sirolimus-eluting stent in routine clinical practice: a 6-month follow-up report from the international e-CYPHER registry. Circulation. 2003; 108 (suppl IV): IV-534. Abstract.Google 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. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Zhao Y, Teng M, Khoo A, Ananthakrishna R, Yeo T, Lim B, Loh J and Chan M (2018) A propensity score-matched comparison of biodegradable polymer vs second-generation durable polymer drug-eluting stents in a real-world population, Cardiovascular Therapeutics, 10.1111/1755-5922.12319, 36:2, (e12319), Online publication date: 1-Apr-2018. Sarkar Das S, Lucas A, Carlin A, Zheng J, Patwardhan D and Saylor D (2016) Controlled initial surge despite high drug fraction and high solubility, Pharmaceutical Development and Technology, 10.3109/10837450.2015.1135341, 22:1, (35-44), Online publication date: 2-Jan-2017. 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