Background Although randomized studies have shown a beneficialeffect of drug-eluting stents in reducing the risk of repeatedrevascularization, these trials were underpowered to comparerates of death and myocardial infarction. The long-term safetyof drug-eluting stents has been questioned recently.
Methods We performed a pooled analysis of 1748 patients in fourrandomized trials evaluating the safety of sirolimus-elutingstents as compared with bare-metal stents. Patient-level datawere obtained and analyzed by independent statisticians at twoacademic institutions. The primary safety end point was survivalat 4 years. We tested for heterogeneities in treatment effectin patient subgroups.
Results The survival rate at 4 years was 93.3% in the sirolimus-stentgroup, as compared with 94.6% in the bare-metal–stentgroup (hazard ratio for death, 1.24; 95% confidence interval[CI], 0.84 to 1.83; P=0.28). In the 428 patients with diabetes,a significant difference in the survival rate was observed infavor of the bare-metal–stent group over the sirolimus-stentgroup (95.6% vs. 87.8%; hazard ratio for death in the sirolimus-stentgroup, 2.9; 95% CI, 1.38 to 6.10; P=0.008). The lower survivalrate among patients with diabetes who were treated with sirolimus-elutingstents was due to increased numbers of deaths from both cardiovascularand noncardiovascular causes. No difference in survival ratewas detected among the patients without diabetes. Rates of myocardialinfarction and stent thrombosis were similar in the two groups.
Conclusions In a pooled analysis of data from four trials comparingsirolimus-eluting stents and bare-metal stents, no significantdifferences were found between the two treatments in rates ofdeath, myocardial infarction, or stent thrombosis. (ClinicalTrials.govnumbers, NCT00233805
[ClinicalTrials.gov]
, NCT00381420
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, NCT00232765
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, and NCT00235144
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.)
Since April 2002, randomized trials and registries have shownthat drug-eluting stents, as compared with bare-metal stents,reduce the need for subsequent revascularization procedures.1,2,3,4,5,6As a result, the use of drug-eluting stents has increased rapidly,with current rates up to 80% of all stenting procedures in somecountries. However, two recent meta-analyses have suggestedthat rates of death and myocardial infarction may be increasedin patients who have received drug-eluting stents.7,8 Impairedreendothelialization, late endothelial dysfunction, hypersensitivityreactions to the stent or its coating, and stent thrombosishave been suggested as potential causes.9,10,11,12,13,14,15,16,17The consequences of even a slight increase in the rates of deathand myocardial infarction would be dramatic, considering thecurrent high rate of use of drug-eluting stents.
The early and pivotal randomized studies that led to approvalof stents for marketing were individually not adequately poweredto detect differences in the rates of death, myocardial infarction,or stent thrombosis. However, reliable long-term data, includinginformation about these end points, are now available and canbe pooled to conduct analyses with greater power than thosein the original trials. We therefore performed a safety analysisof patient-level data collected, in four randomized trials comparingsirolimus-eluting stents and bare-metal stents, during a follow-upperiod of 4 years for 1748 patients.
Methods
Original Trials
Our analysis is based on pooled patient-level data from theRandomized Study with the Sirolimus-Coated Bx Velocity BalloonExpandable Stent in the Treatment of Patients with De Novo NativeCoronary Artery Lesions (RAVEL), the Sirolimus-Eluting Balloon-ExpandableStent in the Treatment of Patients with De Novo Native Coronary-ArteryLesions (SIRIUS) trial, the European SIRIUS (E-SIRIUS) trial,and the Canadian SIRIUS (C-SIRIUS) trial, all of which wereperformed between August 2000 and April 2002. Each of thesefour trials compared a sirolimus-eluting stent (Cypher, Cordis,a Johnson & Johnson company) with a bare-metal stent ofidentical design (Bx Velocity, Cordis), but without polymerand drug coatings, implanted in single, previously untreatedlesions in native coronary arteries, using a double-blind studydesign with a 1:1 randomization process.
The designs of these trials, as well as short-term angiographicand clinical outcomes, have been reported previously.1,2,3,4In summary, RAVEL included patients in clinically stable conditionwith relatively low-risk lesions, whereas the three SIRIUS trialsinvolved patients with higher-risk and more complex lesions.Patients with acute myocardial infarction were excluded in allfour trials. A total of 428 patients with diabetes (treatedthrough diet, with an oral hypoglycemic agent, or with insulin)were included.
Dual antiplatelet therapy with aspirin and clopidogrel or ticlopidinewas prescribed per protocol for a minimum of 2 months in RAVELand the E-SIRIUS and C-SIRIUS trials and for a minimum of 3months in the SIRIUS trial. Aspirin was prescribed indefinitely;doses ranged from 81 to 325 mg daily.
The protocols called for complete angiographic follow-up at6 months (in RAVEL) or at 8 months (in the SIRIUS, E-SIRIUS,and C-SIRIUS studies) and clinical follow-up yearly. The primaryend points differed among the studies and included purely angiographicend points (in-stent late loss in RAVEL and in-stent minimallumen diameter at 8 months in the E-SIRIUS and C-SIRIUS trials)as well as the clinical end point of target-vessel failure (acomposite of death, myocardial infarction, and target-vesselrevascularization) in the SIRIUS trial. Secondary end pointsincluded death, myocardial infarction, and repeated revascularization.
The study protocols were approved by the ethics committee ateach participating institution and were conducted accordingto the principles of the Declaration of Helsinki. All patientsgave written informed consent before enrollment. The studieswere sponsored and monitored by Cordis.
The design of each trial specified in advance that data wouldbe collected for up to 5 years, with adjudication of eventsby the independent end-points committee of the original trial.Four-year follow-up data are currently available from all fourstudies. All clinical follow-up information was collected atthe investigating centers in a blind fashion.
Current Analysis
The databases of the individual studies were obtained from Cordis.Study coordination and data management were performed at twoindependent central research organizations (Cardialysis, Rotterdam,the Netherlands, for RAVEL, and Harvard Clinical Research Institute,Boston, for the SIRIUS, E-SIRIUS and C-SIRIUS studies). Thepatient-level data were pooled and then analyzed by one independentstatistician at Harvard Clinical Research Institute and anotherat Erasmus University Medical Center, Rotterdam. The authorswere given unrestricted access to the data by Cordis and madeall decisions about analysis and publication independently ofthe company.
Study End Points
The primary safety end point was death from any cause. Informationon the circumstances of all deaths was obtained from each ofthe sites, and narratives were developed. These narratives werereviewed by the clinical events committees for the trials and,for the conduct of our analysis, by three of the authors.
Secondary safety end points were death from cardiovascular causesand noncardiovascular causes, death from any cause or Q-wavemyocardial infarction, and death from any cause or any typeof myocardial infarction. The following definitions of eventswere used in all four trials.
Death from cardiovascular causes was defined either as deathdue to acute myocardial infarction, cardiac perforation or pericardialtamponade, arrhythmia or conduction abnormality, cerebrovascularaccident within 30 days or related to the procedure, or a complicationof the procedure or as any death in which a cardiovascular causecould not be ruled out. Death from noncardiovascular causeswas defined as any death not due to a cardiovascular cause.
Q-wave myocardial infarction was defined as the developmentof new, pathologic Q-waves in two or more contiguous leads asassessed by the electrocardiography core laboratory, with creatinekinase or creatine kinase MB levels elevated above the upperlimit of the normal range. Non–Q-wave myocardial infarctionwas defined as an elevation of the creatine kinase MB levelto three times the normal value in the absence of new, pathologicQ-waves; if no assay for creatine kinase MB was performed, elevationof the creatine kinase level to a value that was twice the normalvalue in the absence of new Q-waves was also considered a non–Q-wavemyocardial infarction.
In the study protocols, stent thrombosis was defined as acuteif it occurred within 24 hours after the index procedure, subacuteif it occurred between 1 and 30 days after the procedure, andlate if it occurred more than 30 days after the procedure. Acuteand subacute stent thromboses were classified on the basis ofvessel occlusion on angiography, any recurrent Q-wave myocardialinfarction in an area irrigated by the stented vessel, or deathfrom cardiac causes. Late stent thrombosis was diagnosed onthe basis of any recurrent myocardial infarction with vesselocclusion on angiography. In the original trial protocols, secondarystent thrombosis — stent thrombosis in a patient who hadpreviously undergone target-lesion revascularization —was not considered to be a stent thrombosis.
Stent thrombosis was reclassified in a blind fashion by an independentresearch organization (Harvard Clinical Research Institute)according to a set of definitions developed during summer 2006by the Academic Research Consortium (ARC) of academic investigators,regulators, and industry representatives. These definitionswere proposed to serve as standard criteria for stent thrombosisfor the comparison of event rates across different trials andstudies. According to the ARC definitions, stent thrombosiswas classified as acute if it occurred within 24 hours afterthe index procedure, subacute if it occurred between 1 and 30days after, late if it occurred between 31 days and 1 year after,and very late if it occurred more than 1 year after the procedure.
Furthermore, stent thrombosis was considered definite if therewas angiographic confirmation of thrombus, with or without vesselocclusion, associated with clinical or electrocardiographicsigns of acute ischemia or elevation of creatine kinase levelsto twice the normal value within 48 hours of angiography. Stentthrombosis was classified as probable if unexplained death occurredwithin 30 days after the index procedure or if a myocardialinfarction, occurring at any time after the index procedure,was documented in an area irrigated by the stented vessel inthe absence of angiographic confirmation of stent thrombosis.Stent thrombosis was classified as possible if unexplained deathoccurred more than 30 days after the index procedure. Duringthe readjudication of stent thrombosis according to the ARCdefinitions, events occurring after repeated target-lesion revascularizationwere included.
Statistical Analysis
The effectiveness analysis and safety evaluation were both performedin a modified intention-to-treat population, including all patientswho actually underwent stent placement (whether the procedurewas successful or not). Patients who were randomly assignedto treatment but who did not undergo a procedure were not includedin the analysis.
Summary statistics for all continuous variables are presentedas medians and interquartile ranges. Categorical data are summarizedas frequencies and percentages. Differences in baseline characteristicsbetween the sirolimus-stent group and the bare-metal–stentgroup were analyzed using the Wilcoxon–Mann–Whitneytest or Fisher's exact test.
The incidence of events over time was studied with the use ofthe Kaplan–Meier method, whereas log-rank tests and Coxproportional-hazards regression analyses were applied to evaluatedifferences between the two groups. In the main analysis, hazardratios and 95% confidence intervals (CIs) were adjusted fordifferences in outcome between trials. Follow-up at 1, 2, and3 years was completed for 99.1%, 97.8%, and 96.3% of the patients,respectively. Because follow-up data for the period between1441 and 1460 days were lacking in 675 patients, we decidedto count events through 1440 days, which was interpreted as4 years of follow-up. This 4-year follow-up was completed in90.7% of patients (90.5% of those who received sirolimus-elutingstents and 90.9% of those who received bare-metal stents).
Exploratory analyses (not prespecified) were performed to evaluatepossible heterogeneities in treatment effects on mortality accordingto the trial in which the patient was enrolled and the following10 clinically relevant characteristics: age, sex, diabetes,dyslipidemia, hypertension, prior myocardial infarction, heartfailure, angina classification by the Canadian CardiovascularSociety, number of diseased vessels, and left ventricular ejectionfraction.5 Since a clinically relevant difference in treatmenteffect on mortality was observed in relation to diabetes status,we decided to study other end points in patients with and thosewithout diabetes. Treatment effects were evaluated with theuse of Cox regressions that included a term for the interactionbetween each characteristic of interest and the assigned treatment,adjusted for differences in outcome between trials. More extensiveregression models incorporating predictive baseline characteristicswere applied to estimate the adjusted treatment effects.18
All statistical tests were two-sided, without correction formultiple testing. P values of less than 0.05 and less than 0.01were considered to indicate statistical significance for theresults of nonheterogeneity tests and tests for heterogeneityin treatment effect, respectively. All statistical analyseswere performed with the use of SAS software, version 8.2 (SASInstitute).
Results
A total of 1748 patients were included in this analysis (238in RAVEL, 1058 in the SIRIUS study, 100 in the C-SIRIUS study,and 352 in the E-SIRIUS study). In total, 878 patients underwentplacement of a sirolimus-eluting stent, and 870 patients underwentplacement of a bare-metal stent. The clinical and angiographiccharacteristics of the study patients are summarized in Table 1.Complex lesions were more frequent in patients with sirolimus-elutingstents than in patients with bare-metal stents (22.5% vs. 18.5%,P=0.04), and diabetes was more common in the bare-metal–stentgroup than in the sirolimus-stent group (26.8% vs. 22.2%, P=0.02).
Table 1. Baseline Clinical and Angiographic Characteristics.
Results for all patients are shown in Table 2 and Figure 1.The 4-year cumulative survival rate was slightly, but not significantly,lower in the sirolimus-stent group than in the bare-metal–stentgroup (93.3% and 94.6%, respectively; hazard ratio for deathin the sirolimus group, 1.24; 95% CI, 0.84 to 1.83; P=0.28).Narratives of all patient deaths revealed that mortality fromboth cardiovascular and noncardiovascular causes was slightly,but not significantly, higher in the sirolimus-stent group (Table 2and the Supplementary Appendix, available with the full textof this article at www.nejm.org). Rates of myocardial infarctionoverall were similar between the two groups. Rates of Q-wavemyocardial infarction were also slightly, but not significantly,higher in the sirolimus-stent group.
Figure 1. Kaplan–Meier Survival Curves for Patients Who Received a Sirolimus-Eluting Stent and Those Who Received a Bare-Metal Stent.
Panel A shows overall survival; Panel B shows freedom from death or myocardial infarction (MI). The survival rates at 1440 days are shown in parentheses. P values were calculated with the use of the log-rank test.
According to the protocol definitions, there were 10 stent thrombosesin the sirolimus-stent group and 5 in the bare-metal–stentgroup (Table 2). Five of the thromboses in the sirolimus-stentgroup, but none in the bare-metal–stent group, occurredafter 1 year. In contrast, according to the ARC definitions,there were 30 stent thromboses in the sirolimus-stent groupand 28 in the bare-metal–stent group (Figure 2). Stentthrombosis was more frequent in the bare-metal–stent groupin the first year (14, vs. 6 in the sirolimus-stent group),whereas very late stent thrombosis (occurring after the firstyear) was more frequent in the sirolimus-stent group (23, vs.14 in the bare-metal–stent group).
Figure 2. Kaplan–Meier Curves for the Survival of Patients without Stent Thrombosis as Defined by the ARC.
All first episodes of stent thrombosis were counted, including those that occurred after revascularization of the target lesion. The survival rates at 1440 days are shown in parentheses. The P value was calculated with the use of the log-rank test.
Significant heterogeneity in the treatment effects was not foundfor any of the prespecified subgroups except patients with diabetes(P value for interaction=0.008) (see the Supplementary Appendix).The 4-year cumulative survival rates among patients withoutdiabetes did not differ significantly between the two groups.However, the survival rate for patients with diabetes was significantlylower in the sirolimus-stent group (87.8%, vs. 95.6% in thebare-metal–stent group; hazard ratio for death, 2.90;95% CI, 1.38 to 6.10; P=0.008) (Figure 3 and the Supplementary Appendix).A large heterogeneity in the causes of death of the patientswith diabetes precluded the identification of a clear patternof mortality (see the Supplementary Appendix). Among the patientswith diabetes, there was a small excess of very late stent thrombosisas defined by the ARC (occurring more than 1 year after theprocedure) in the sirolimus-stent group (11 patients, vs. 3in the bare-metal–stent group) (see the Supplementary Appendix).
Figure 3. Kaplan–Meier Survival Curves for Patients with Diabetes and Those without Diabetes.
The survival rates at 1440 days are shown in parentheses. P values were calculated with the use of the log-rank test.
Discussion
In this study, we performed a pooled analysis of four randomizedtrials comparing sirolimus-eluting stents and bare-metal stentsin 1748 patients with 4 years of follow-up. We did not findevidence of a significantly higher rate of death, myocardialinfarction, or stent thrombosis in the patients treated withsirolimus-eluting stents. The divergence of the Kaplan–Meiersurvival curves over time could be interpreted as a growingtrend toward a lower survival rate among patients treated withsirolimus-eluting stents as compared with those treated withbare-metal stents, although a larger number of patients, a longerfollow-up period, or both would be necessary to confirm thisinterpretation.
In our study, we analyzed rates of stent thrombosis adjudicatedaccording to the definitions in the original protocols and thoseof the ARC. We believe that this provides a more accurate pictureof the incidence of stent thrombosis with either type of stent,for two reasons. First, late events such as unexplained death,which were not considered in the original protocols, were adjudicatedas possible stent thrombosis. Second, all episodes of stentthrombosis, including those occurring after target-lesion revascularization,were included in the readjudicated event rates.
A significant heterogeneity of the treatment effect was foundwith respect to diabetes. A significantly reduced survival ratewas found among patients with diabetes (but not patients withoutdiabetes) treated with sirolimus-eluting stents. Deaths fromcardiovascular and noncardiovascular causes were more frequentin the sirolimus-stent group. In the subgroup of patients withdiabetes, very late stent thrombosis was adjudicated more frequentlyamong the patients with sirolimus-eluting stents than amongthose with bare-metal stents. Owing to the low number of events,these findings should be interpreted with caution; it does notappear that they adequately explain the observed differencein survival among patients with diabetes in the two groups.
Previous studies have reached different conclusions regardingthe benefit of drug-eluting stents in patients with diabetes.The 9-month results of a dedicated randomized trial of patientswith diabetes showed that sirolimus-eluting stents were superiorto bare-metal stents in reducing rates of both restenosis andrepeated revascularization.19 Mortality at 9 months was only1% in the sirolimus-stent group, as compared with 2% in thebare-metal–stent group. Conversely, the 2-year follow-upof 708 patients with diabetes from a large registry on the useof drug-eluting stents revealed a mortality of 13.3% among patientstreated with sirolimus-eluting stents, as compared with 9.8%among patients treated with bare-metal stents.20 Although thedifference in mortality was not significant, a hazard ratiofor death of 1.55 remained after a propensity analysis. In addition,the rate of angiographically proven stent thrombosis in thatstudy was 4.4% in the sirolimus-stent group but only 0.8% inthe bare-metal–stent group. Finally, diabetes has beenshown to be a consistent independent predictor of stent thrombosisin patients treated with drug-eluting stents.21,22
Several limitations of our study should be considered. The analysiswas underpowered to detect a clinically significant differencein mortality; more than 11,000 patients would have been neededfor such an analysis. Patients included in the four randomizedtrials were highly selected and are representative of only about25% of patients currently treated with drug-eluting stents.Treatment with clopidogrel was required for at least 2 or 3months, according to the original trial protocols, but no informationon actual use by individual patients, even by those who hadadverse events, was available. Thus, we cannot provide any specificinsight into the question of whether prolonging dual antiplatelettherapy further would reduce the risk of such events. We performedmultiple subgroup analyses that were not prespecified, includingone for diabetes. The number of fatal events in patients withdiabetes was small, so the related findings may be due to chance.Finally, lower-than-expected mortality was noted among the patientswith diabetes in the bare-metal–stent group, for reasonsthat remain unclear.
In summary, in our pooled analysis of data from four randomizedtrials, we compared the effects of sirolimus-eluting stentswith those of bare-metal stents on clinical events at 4 years.No significant differences in the rates of death, myocardialinfarction, or stent thrombosis were found.
Dr. Spaulding reports receiving consulting and lecture feesfrom Cordis, Boston Scientific, and Guidant. No other potentialconflict of interest relevant to this article was reported.
We thank Dr. J. Massaro (Harvard Clinical Research Institute,Boston) for the statistical analysis; H.-P. Stoll (Cordis, Waterloo,Belgium) for his assistance in the transfer of the data; andDrs. M.C. Morice, J.W. Moses, E. Schampaert, and J. Schoferfor their roles as the principal investigators of the four randomizedtrials: RAVEL, SIRIUS, C-SIRIUS, and E-SIRIUS, respectively.
Source Information
From Assistance Publique–Hôpitaux de Paris Cochin Hospital, Paris 5 Medical School René Descartes University and INSERM Unité 780 Avenir, Paris (C.S.); Erasmus Medical Center, Rotterdam, the Netherlands (J.D., E.B., P.W.S.); and Harvard Clinical Research Institute, Boston (D.E.C.). Drs. Spaulding and Daemen contributed equally to this article. This article (10.1056/NEJMoa066633) was published at www.nejm.org on February 12, 2007.
Address reprint requests to Dr. Serruys at Thoraxcentrum, Erasmus University, Dr. Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands, or at p.w.j.c.serruys{at}erasmusmc.nl.
References
Morice MC, Serruys PW, Sousa JE, et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med 2002;346:1773-1780. [Free Full Text]
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315-1323. [Free Full Text]
Schampaert E, Cohen EA, Schluter M, et al. The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol 2004;43:1110-1115. [Free Full Text]
Schofer J, Schluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS). Lancet 2003;362:1093-1099. [CrossRef][ISI][Medline]
Daemen J, Ong AT, Stefanini G, et al. Three-year clinical follow-up of the unrestricted use of sirolimus-eluting stents as part of the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry. Am J Cardiol 2006;98:895-901. [CrossRef][ISI][Medline]
Urban P, Gershlick AH, Guagliumi G, et al. Safety of coronary sirolimus-eluting stents in daily clinical practice: one-year follow-up of the e-Cypher registry. Circulation 2006;113:1434-1441. [Free Full Text]
Nordmann AJ, Briel M, Bucher HC. Mortality in randomized controlled trials comparing drug-eluting vs. bare metal stents in coronary artery disease: a meta-analysis. Eur Heart J 2006;27:2784-2814. [Free Full Text]
Camenzind E. Do drug-eluting stents increase death? European Society of Cardiology Congress News. September 5, 2006.
Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 2006;48:193-202. [Free Full Text]
Virmani R, Guagliumi G, Farb A, et al. Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation 2004;109:701-705. [Free Full Text]
McFadden EP, Stabile E, Regar E, et al. Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet 2004;364:1519-1521. [CrossRef][ISI][Medline]
Nebeker JR, Virmani R, Bennett CL, et al. Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. J Am Coll Cardiol 2006;47:175-181. [Free Full Text]
Hofma SH, van der Giessen WJ, van Dalen BM, et al. Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation. Eur Heart J 2006;27:166-170. [Free Full Text]
Babinska A, Markell MS, Salifu MO, Akoad M, Ehrlich YH, Kornecki E. Enhancement of human platelet aggregation and secretion induced by rapamycin. Nephrol Dial Transplant 1998;13:3153-3159. [Free Full Text]
Sianos G, Hofma S, Ligthart JM, et al. Stent fracture and restenosis in the drug-eluting stent era. Catheter Cardiovasc Interv 2004;61:111-116. [CrossRef][ISI][Medline]
Scheller B, Grandt A, Wnendt S, Lorenz G, Bohm M, Nickenig G. Comparative study of tacrolimus and paclitaxel stent coating in the porcine coronary model. Z Kardiol 2005;94:445-452. [CrossRef][ISI][Medline]
Daemen J, Wenaweser P, Tsuchida K, et al. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet (in press).
Steyerberg EW, Bossuyt PM, Lee KL. Clinical trials in acute myocardial infarction: should we adjust for baseline characteristics? Am Heart J 2000;139:745-751. [ISI][Medline]
Sabate M, Jimenez-Quevedo P, Angiolillo DJ, et al. Randomized comparison of sirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients: the diabetes and sirolimus-eluting stent (DIABETES) trial. Circulation 2005;112:2175-2183. [Free Full Text]
Daemen J, Garcia-Garcia HM, Kukreja N, et al. The long-term value of sirolimus- and paclitaxel-eluting stents over bare metal stents in patients with diabetes mellitus. Eur Heart J 2007;28:26-32. [Free Full Text]
Ong AT, McFadden EP, Regar E, de Jaegere PP, van Domburg RT, Serruys PW. Late angiographic stent thrombosis (LAST) events with drug-eluting stents. J Am Coll Cardiol 2005;45:2088-2092. [Free Full Text]
Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126-2130. [Free Full Text]
Yau, L., Molnar, P., Moon, M. C., Buhay, S., Werner, J. P., Molnar, K., Saward, L., Del Rizzo, D., Zahradka, P.
(2008). meta-Iodobenzylguanidine, an Inhibitor of Arginine-Dependent Mono(ADP-ribosyl)ation, Prevents Neointimal Hyperplasia. J. Pharmacol. Exp. Ther.
326: 717-724
[Abstract][Full Text]
Chieffo, A., Park, S.-J., Meliga, E., Sheiban, I., Lee, M. S., Latib, A., Kim, Y.-H., Valgimigli, M., Sillano, D., Magni, V., Biondi-Zoccai, G., Montorfano, M., Airoldi, F., Rogacka, R., Carlino, M., Michev, I., Lee, C.-W., Hong, M.-K., Park, S.-W., Moretti, C., Bonizzoni, E., Sangiorgi, G. M., Tobis, J., Serruys, P. W., Colombo, A.
(2008). Late and very late stent thrombosis following drug-eluting stent implantation in unprotected left main coronary artery: a multicentre registry. Eur Heart J
29: 2108-2115
[Abstract][Full Text]
Stettler, C., Allemann, S., Wandel, S., Kastrati, A., Morice, M. C., Schomig, A., Pfisterer, M. E, Stone, G. W, Leon, M. B, Lezo, J. S. d., Goy, J.-J., Park, S.-J., Sabate, M., Suttorp, M. J, Kelbaek, H., Spaulding, C., Menichelli, M., Vermeersch, P., Dirksen, M. T, Cervinka, P., Carlo, M. D., Erglis, A., Chechi, T., Ortolani, P., Schalij, M. J, Diem, P., Meier, B., Windecker, S., Juni, P.
(2008). Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis. BMJ
337: a1331-a1331
[Abstract][Full Text]
Agostoni, P., Branden, F. V. d.
(2008). Drug eluting stents in patients with diabetes. BMJ
337: a1359-a1359
[Full Text]
Austin, D., Oldroyd, K. G., McConnachie, A., Slack, R., Eteiba, H., Flapan, A. D., Jennings, K. P., Northcote, R. J., Pell, A. C.H., Starkey, I. R., Pell, J. P.
(2008). Drug-Eluting Stents Versus Bare-Metal Stents for Off-Label Indications: A Propensity Score-Matched Outcome Study. Circ Cardiovasc Intervent
1: 45-52
[Abstract][Full Text]
Brodie, B. R., Stuckey, T., Downey, W., Humphrey, A., Bradshaw, B., Metzger, C., Hermiller, J., Krainin, F., Juk, S., Cheek, B., Duffy, P., Smith, H., Edmunds, J., Varanasi, J., Simonton, C. A., STENT (Strategic Transcatheter Evaluation of New T,
(2008). Outcomes and Complications With Off-Label Use of Drug-Eluting Stents: Results From the STENT (Strategic Transcatheter Evaluation of New Therapies) Group. J Am Coll Cardiol Intv
1: 405-414
[Abstract][Full Text]
Newsome, L. T., Kutcher, M. A., Royster, R. L.
(2008). Coronary Artery Stents: Part I. Evolution of Percutaneous Coronary Intervention. Anesth. Analg.
107: 552-569
[Abstract][Full Text]
Booth, J., Clayton, T., Pepper, J., Nugara, F., Flather, M., Sigwart, U., Stables, R. H., on Behalf of the SoS Investigators,
(2008). Randomized, Controlled Trial of Coronary Artery Bypass Surgery Versus Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease: Six-Year Follow-Up From the Stent or Surgery Trial (SoS). Circulation
118: 381-388
[Abstract][Full Text]
Malenka, D. J., Kaplan, A. V., Lucas, F. L., Sharp, S. M., Skinner, J. S.
(2008). Outcomes Following Coronary Stenting in the Era of Bare-Metal vs the Era of Drug-Eluting Stents. JAMA
299: 2868-2876
[Abstract][Full Text]
Alfonso, F.
(2008). The "vulnerable" stent why so dreadful?. J Am Coll Cardiol
51: 2403-2406
[Full Text]
Dixon, S. R., Grines, C. L., O'Neill, W. W.
(2008). The year in interventional cardiology.. J Am Coll Cardiol
51: 2355-2369
[Full Text]
Brar, S. S., Kim, J., Brar, S. K., Zadegan, R., Ree, M., Liu, I.-L. A., Mansukhani, P., Aharonian, V., Hyett, R., Shen, A. Y.-J.
(2008). Long-term outcomes by clopidogrel duration and stent type in a diabetic population with de novo coronary artery lesions.. J Am Coll Cardiol
51: 2220-2227
[Abstract][Full Text]
Austin, D., Oldroyd, K. G., McConnachie, A., Slack, R., Eteiba, H., Flapan, A. D., Jennings, K. P., Northcote, R. J., Pell, A. C. H., Starkey, I. R., Pell, J. P.
(2008). Hospital and operator variations in drug-eluting stent use: a multi-level analysis of 5967 consecutive patients in Scotland. J Public Health (Oxf)
30: 186-193
[Abstract][Full Text]
Li, J., Jabara, R., Pendyala, L., Otsuka, Y., Shinke, T., Hou, D., Robinson, K., Chronos, N.
(2008). Abnormal Vasomotor Function of Porcine Coronary Arteries Distal to Sirolimus-Eluting Stents. J Am Coll Cardiol Intv
1: 279-285
[Abstract][Full Text]
Kelbaek, H., Klovgaard, L., Helqvist, S., Lassen, J. F., Krusell, L. R., Engstrom, T., Botker, H. E., Jorgensen, E., Saunamaki, K., Aljabbari, S., Thayssen, P., Galloe, A., Jensen, G. V.H., Thuesen, L.
(2008). Long-Term Outcome in Patients Treated With Sirolimus-Eluting Stents in Complex Coronary Artery Lesions: 3-Year Results of the SCANDSTENT (Stenting Coronary Arteries in Non-Stress/Benestent Disease) Trial. J Am Coll Cardiol
51: 2011-2016
[Abstract][Full Text]
Groeneveld, P. W., Matta, M. A., Greenhut, A. P., Yang, F.
(2008). Drug-Eluting Compared With Bare-Metal Coronary Stents Among Elderly Patients. J Am Coll Cardiol
51: 2017-2024
[Abstract][Full Text]
Bhatt, S. H, Hauser, T. H
(2008). Very Late Stent Thrombosis After Dual Antiplatelet Therapy Discontinuation in a Patient with a History of Acute Stent Thrombosis. The Annals of Pharmacotherapy
42: 708-712
[Abstract][Full Text]
Stone, G. W., Midei, M., Newman, W., Sanz, M., Hermiller, J. B., Williams, J., Farhat, N., Mahaffey, K. W., Cutlip, D. E., Fitzgerald, P. J., Sood, P., Su, X., Lansky, A. J., for the SPIRIT III Investigators,
(2008). Comparison of an Everolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients With Coronary Artery Disease: A Randomized Trial. JAMA
299: 1903-1913
[Abstract][Full Text]
Patel, M. R., Holmes, D. R. Jr
(2008). Next-Generation Drug-Eluting Stents: A Spirited Step Forward or More of the Same. JAMA
299: 1952-1953
[Full Text]
Hannan, E. L., Racz, M., Holmes, D. R., Walford, G., Sharma, S., Katz, S., Jones, R. H., King, S. B. III
(2008). Comparison of Coronary Artery Stenting Outcomes in the Eras Before and After the Introduction of Drug-Eluting Stents. Circulation
117: 2071-2078
[Abstract][Full Text]
Kapadia, M. R., Popowich, D. A., Kibbe, M. R.
(2008). Modified Prosthetic Vascular Conduits. Circulation
117: 1873-1882
[Abstract][Full Text]
Mulukutla, S. R., Vlachos, H. A., Marroquin, O. C., Selzer, F., Holper, E. M., Abbott, J. D., Laskey, W. K., Williams, D. O., Smith, C., Anderson, W. D., Lee, J. S., Srinivas, V., Kelsey, S. F., Kip, K. E.
(2008). Impact of Drug-Eluting Stents Among Insulin-Treated Diabetic Patients: A Report From the National Heart, Lung, and Blood Institute Dynamic Registry. J Am Coll Cardiol Intv
1: 139-147
[Abstract][Full Text]
Marso, S. P.
(2008). Diabetes and Drug-Eluting Stents: What You Get and What You Don't. J Am Coll Cardiol Intv
1: 148-149
[Full Text]
Zellweger, M. J., Kaiser, C., Brunner-La Rocca, H. P., Buser, P. T., Osswald, S., Weiss, P., Mueller-Brand, J., Pfisterer, M. E., for the BASKET Investigators,
(2008). Value and Limitations of Target-Vessel Ischemia in Predicting Late Clinical Events After Drug-Eluting Stent Implantation. JNM
49: 550-556
[Abstract][Full Text]
Billinger, M., Beutler, J., Taghetchian, K. R., Remondino, A., Wenaweser, P., Cook, S., Togni, M., Seiler, C., Stettler, C., Eberli, F. R., Luscher, T. F., Wandel, S., Juni, P., Meier, B., Windecker, S.
(2008). Two-year clinical outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents in diabetic patients. Eur Heart J
29: 718-725
[Abstract][Full Text]
Hoffmann, R, Morice, M-C, Moses, J W, Fitzgerald, P J, Mauri, L, Breithardt, G, Schofer, J, Serruys, P W, Stoll, H-P, Leon, M B
(2008). Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials. Heart
94: 322-328
[Abstract][Full Text]
Kirtane, A. J., Ellis, S. G., Dawkins, K. D., Colombo, A., Grube, E., Popma, J. J., Fahy, M., Leon, M. B., Moses, J. W., Mehran, R., Stone, G. W.
(2008). Paclitaxel-Eluting Coronary Stents in Patients With Diabetes Mellitus Pooled Analysis From 5 Randomized Trials.. J Am Coll Cardiol
51: 708-715
[Abstract][Full Text]
Ortolani, P., Balducelli, M., Marzaroli, P., Piovaccari, G., Menozzi, A., Guiducci, V., Sangiorgio, P., Tarantino, F., Geraci, G., Castriota, F., Tondi, S., Saia, F., Cooke, R. M.T., Guastaroba, P., Grilli, R., Marzocchi, A., Maresta, A.
(2008). Two-Year Clinical Outcomes With Drug-Eluting Stents for Diabetic Patients With De Novo Coronary Lesions: Results From a Real-World Multicenter Registry. Circulation
117: 923-930
[Abstract][Full Text]
Jeremias, A., Kirtane, A.
(2008). Balancing Efficacy and Safety of Drug-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention. ANN INTERN MED
148: 234-238
[Abstract][Full Text]
Austin, D., Pell, J. P, Oldroyd, K. G
(2008). Drug-eluting stents: do the risks really outweigh the benefits?. Heart
94: 127-128
[Full Text]
Melikian, N, Wijns, W
(2008). Drug-eluting stents: a critique. Heart
94: 145-152
[Abstract][Full Text]
Holmes, D. R. Jr, Gersh, B. J., Whitlow, P., King, S. B. III, Dove, J. T.
(2008). Percutaneous Coronary Intervention for Chronic Stable Angina: A Reassessment. J Am Coll Cardiol Intv
1: 34-43
[Abstract][Full Text]
American College of Cardiology/American Heart Asso, , 2007 Writing Group to Review New Evidence and Upda, , King, S. B. III, Smith, S. C. Jr, Hirshfeld, J. W. Jr, Jacobs, A. K., Morrison, D. A., Williams, D. O.
(2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. J Am Coll Cardiol
51: 172-209
[Full Text]
King, S. B. III, Smith, S. C. Jr, Hirshfeld, J. W. Jr, Jacobs, A. K., Morrison, D. A., Williams, D. O., 2005 WRITING COMMITTEE MEMBERS, , Smith, S. C. Jr, Feldman, T. E., Hirshfeld, J. W. Jr, Jacobs, A. K., Kern, M. J., King, S. B. III, Morrison, D. A., O'Neill, W. W., Schaff, H. V., Whitlow, P. L., Williams, D. O., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Buller, C. E., Creager, M. A., Ettinger, S. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Page, R. L., Riegel, B., Tarkington, L. G., Yancy, C. W.
(2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, Writing on Behalf of the 2005 Writing Committee. Circulation
117: 261-295
[Full Text]
Singh, S., Arora, R., Khraisat, A., Handa, K., Bahekar, A., Trivedi, A., Khosla, S.
(2007). Increased Incidence of In-Stent Thrombosis Related to Cocaine Use: Case Series and Review of Literature. J CARDIOVASC PHARMACOL THER
12: 298-303
[Abstract]
Unger, F.
(2007). Drug eluting stents a nightmare?. ICVTS
6: 813-814
[Abstract][Full Text]
Abbott, J. D., Voss, M. R., Nakamura, M., Cohen, H. A., Selzer, F., Kip, K. E., Vlachos, H. A., Wilensky, R. L., Williams, D. O.
(2007). Unrestricted Use of Drug-Eluting Stents Compared With Bare-Metal Stents in Routine Clinical Practice: Findings From the National Heart, Lung, and Blood Institute Dynamic Registry. J Am Coll Cardiol
50: 2029-2036
[Abstract][Full Text]
Lamas, G. A, Hochman, J. S
(2007). Where does the Occluded Artery Trial leave the late open artery hypothesis?. Heart
93: 1319-1321
[Abstract][Full Text]
Iijima, R., Mehilli, J., Schomig, A., Kastrati, A.
(2007). Abstract 2147: Drug-Eluting Stents Versus Bare Metal Stents in Diabetic Patients With Acute Myocardial Infarction: A Pooled Patient-Level Analysis of 7 Randomized Trials.. Circulation
116: II_465-II_465
Fleisher, L. A., Beckman, J. A., Brown, K. A., Calkins, H., Chaikof, E. L., Fleischmann, K. E., Freeman, W. K., Froehlich, J. B., Kasper, E. K., Kersten, J. R., Riegel, B., Robb, J. F., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Buller, C. E., Creager, M. A., Ettinger, S. M., Faxon, D. P., Fuster, V., Halperin, J. L., Hiratzka, L. F., Hunt, S. A., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B., Tarkington, L. G., Yancy, C. W.
(2007). ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery) Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. J Am Coll Cardiol
50: e159-e242
[Full Text]
Windecker, S., Meier, B.
(2007). Late Coronary Stent Thrombosis. Circulation
116: 1952-1965
[Full Text]
Fleisher, L. A., Beckman, J. A., Brown, K. A., Calkins, H., Chaikof, E. L., Fleischmann, K. E., Freeman, W. K., Froehlich, J. B., Kasper, E. K., Kersten, J. R., Riegel, B., Robb, J. F.
(2007). ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation
116: e418-e500
[Full Text]
Camenzind, E., Steg, P. G., Wijns, W.
(2007). Response to Letter Regarding Article, "Stent Thrombosis Late After Implantation of First-Generation Drug-Eluting Stents: A Cause for Concern". Circulation
116: e390-e390
[Full Text]
Tu, J. V., Bowen, J., Chiu, M., Ko, D. T., Austin, P. C., He, Y., Hopkins, R., Tarride, J.-E., Blackhouse, G., Lazzam, C., Cohen, E. A., Goeree, R.
(2007). Effectiveness and Safety of Drug-Eluting Stents in Ontario. NEJM
357: 1393-1402
[Abstract][Full Text]
Rodriguez, A. E., Maree, A. O., Mieres, J., Berrocal, D., Grinfeld, L., Fernandez-Pereira, C., Curotto, V., Rodriguez-Granillo, A., O'Neill, W., Palacios, I. F.
(2007). Late loss of early benefit from drug-eluting stents when compared with bare-metal stents and coronary artery bypass surgery: 3 years follow-up of the ERACI III registry. Eur Heart J
28: 2118-2125
[Abstract][Full Text]
Chassot, P.-G., Delabays, A., Spahn, D. R.
(2007). Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. Br J Anaesth
99: 316-328
[Abstract][Full Text]
Daemen, J., Serruys, P. W.
(2007). Drug-Eluting Stent Update 2007: Part II: Unsettled Issues. Circulation
116: 961-968
[Full Text]
Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B.
(2007). ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol
50: e1-e157
[Full Text]
Bode, C., Zehender, M.
(2007). The use of antiplatelet agents following percutaneous coronary intervention: focus on late stent thrombosis. Eur Heart J Suppl
9: D10-D19
[Abstract][Full Text]
Jensen, L. O., Maeng, M., Kaltoft, A., Thayssen, P., Hansen, H. H. T., Bottcher, M., Lassen, J. F., Krussel, L. R., Rasmussen, K., Hansen, K. N., Pedersen, L., Johnsen, S. P., Soerensen, H. T., Thuesen, L.
(2007). Stent Thrombosis, Myocardial Infarction, and Death After Drug-Eluting and Bare-Metal Stent Coronary Interventions. J Am Coll Cardiol
50: 463-470
[Abstract][Full Text]
Kaul, S., Shah, P. K., Diamond, G. A.
(2007). As Time Goes By: Current Status and Future Directions in the Controversy Over Stenting. J Am Coll Cardiol
50: 128-137
[Abstract][Full Text]
Jaffe, R., Strauss, B. H.
(2007). Late and Very Late Thrombosis of Drug-Eluting Stents: Evolving Concepts and Perspectives. J Am Coll Cardiol
50: 119-127
[Abstract][Full Text]
Holmes, D. R. Jr, Kereiakes, D. J., Laskey, W. K., Colombo, A., Ellis, S. G., Henry, T. D., Popma, J. J., Serruys, P. W.J.C., Kimura, T., Williams, D. O., Windecker, S., Krucoff, M. W.
(2007). Thrombosis and Drug-Eluting Stents: An Objective Appraisal. J Am Coll Cardiol
50: 109-118
[Abstract][Full Text]
Spinler, S. A., Wilensky, R. L.
(2007). Duration of clopidogrel therapy after placement of drug-eluting intracoronary stent. Am J Health Syst Pharm
64: 1432-1434
[Full Text]
Finn, A. V., Nakazawa, G., Joner, M., Kolodgie, F. D., Mont, E. K., Gold, H. K., Virmani, R.
(2007). Vascular Responses to Drug Eluting Stents: Importance of Delayed Healing. Arterioscler. Thromb. Vasc. Bio.
27: 1500-1510
[Abstract][Full Text]
Krucoff, M. W., Boam, A., Schultz, D. G.
(2007). Drug-Eluting Stents "Deliver Heartburn": How Do We Spell Relief Going Forward?. Circulation
115: 2990-2994
[Full Text]
(2007). From the Library. Br. J. Ophthalmol.
91: 846-846
[Full Text]
Harrington, R. A., Ohman, E. M.
(2007). The Enigma of Drug-Eluting Stents: Hope, Hype, Humility, and Advancing Patient Care. JAMA
297: 2028-2030
[Full Text]
Boden, W. E., O'Rourke, R. A., Teo, K. K., Hartigan, P. M., Maron, D. J., Kostuk, W. J., Knudtson, M., Dada, M., Casperson, P., Harris, C. L., Chaitman, B. R., Shaw, L., Gosselin, G., Nawaz, S., Title, L. M., Gau, G., Blaustein, A. S., Booth, D. C., Bates, E. R., Spertus, J. A., Berman, D. S., Mancini, G.B. J., Weintraub, W. S., the COURAGE Trial Research Group,
(2007). Optimal Medical Therapy with or without PCI for Stable Coronary Disease. NEJM
356: 1503-1516
[Abstract][Full Text]
Serruys, P. W., Daemen, J.
(2007). Late Stent Thrombosis: A Nuisance in Both Bare Metal and Drug-Eluting Stents. Circulation
115: 1433-1439
[Full Text]
Curfman, G. D., Morrissey, S., Jarcho, J. A., Drazen, J. M.
(2007). Drug-Eluting Coronary Stents -- Promise and Uncertainty. NEJM
356: 1059-1060
[Full Text]
(2007). Latest Findings on Stents. JWatch General
2007: 1-1
[Full Text]
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