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Clinical Outcomes After Unrestricted Implantation of Everolimus-Eluting Stents

Azeem Latib, MB BCh^_*,, Luca Ferri, MD^_*, Alfonso Ielasi, MD^_*, Cosmo Godino, MD^_*,, Alaide Chieffo, MD^_*, Valeria Magni, MD^_*, Giorgio Bassanelli, MD^_*, Andrew S.P. Sharp, MD, Robert Gerber, MD, Iassen Michev, MD^_*,, Mauro Carlino, MD^_*, Flavio Airoldi, MD^_*, Giuseppe M. Sangiorgi, MD, Matteo Montorfano, MD^_*, Antonio Colombo, MD^_*,,_*

^_* Interventional Cardiology Unit, San Raffaele Scientific Institute, Milan, Italy
Interventional Cardiology Unit, EMO Centro Cuore Columbus, Milan, Italy
Division of Cardiology, University of Cape Town, Cape Town, South Africa

	Abstract

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Objectives: The aim of this study was to evaluate the efficacy and safety of unrestricted everolimus-eluting stent (EES) implantation in a contemporary cohort of real-world patients.

Background: The randomized SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trials have evaluated the performance of EES, resulting in their approval by the Food and Drug Administration, but data regarding unselected usage, including off-label indications are lacking.

Methods: Consecutive patients treated with EES (either PROMUS, Boston Scientific Corp., Natick, Massachusetts, or XIENCE-V, Abbott Vascular Devices, Santa Clara, California) between October 2006 and February 2008 were analyzed. End points were cardiac death, myocardial infarction (MI), ischemic-driven target lesion revascularization (TLR), stent thrombosis (ST), and major adverse cardiac events (MACE) (a composite of cardiac death, MI, TLR) during follow-up.

Results: We identified 345 patients (573 lesions) treated with EES. The majority of patients (71.9%) were treated for 1 off-label or untested indication. Clinical follow-up was completed in 99%. At a median follow-up of 378 days (interquartile range 334 to 473), MACE occurred in 36 (10.6%) patients, TLR in 27 (7.9%), MI in 7 (2.1%), and cardiac death in 7 (2.1%). Definite and probable ST was observed in 3 (0.9%) cases. Off-label EES implantation was not associated with a statistically significant increased risk of MACE (12.2% vs. 6.3%, p = 0.17), TLR (9.3% vs. 4.2%, p = 0.18), or ST (0.8% vs. 1.1%, p = 1.0). On multivariable analysis, previous bypass surgery (p = 0.002) and diabetes (p = 0.03) were associated with MACE.

Conclusions: In unrestricted daily practice, EES were implanted predominantly for off-label indications and associated with a relative low rate of MACE and TLR.

Key Words: drug-eluting stent • everolimus-eluting stent • off-label • outcomes • real world

Abbreviations and Acronyms   BMS = bare-metal stent(s)   CI = confidence interval   DES = drug-eluting stent(s)   EES = everolimus-eluting stent(s)   FDA = Food and Drug Administration   IVUS = intravascular ultrasound   MACE = major adverse cardiac events   MI = myocardial infarction   ST = stent thrombosis   TLR = target lesion revascularization   TVR = target vessel revascularization

However, when DES are implanted in everyday clinical practice, they are often implanted for off-label indications in complex patients and lesions where the benefit in reducing restenosis and repeat revascularization might be greater (7,8). As has been seen with the first-generation DES, the clinical event rates are often higher in real world registries compared with those seen in the randomized trials, and as a result, concerns have been raised about the efficacy and safety in off-label indications (9–12). Data regarding EES in these complex patients and lesions are lacking. Thus we sought to evaluate the clinical outcomes of unrestricted EES implantation in daily practice.

	Methods

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All consecutive patients successfully treated with only EES implantation at our center between October 2006 (when EES became available in our institution) and February 2008 (in order to have a minimum of 1-year follow-up in most patients) were included in this retrospective analysis. Stent selection, although at the operator's discretion, was carried out in an aleatory fashion during the study period. Selecting an EES over another DES was performed without any specific preference and not based on patient risk or lesion morphology. It is the usual practice in our institutions to alternate the implantation of different types of DES. We provide a flow chart in Figure 1 describing the selection of bare-metal stents (BMS) and different DES at our institutions during the period of this study. The only exclusion criteria were a mixture of different types of DES or a mixture of BMS and DES. Also patients undergoing primary angioplasty for ST-segment elevation myocardial infarction (MI) were excluded, because it is the practice of our institution not to implant a DES in these patients. All patients provided informed consent for both the procedure and subsequent data collection.

View larger version (8K): [in this window] [in a new window] [Download PPT slide]   Figure 1 A Flow Chart Describing Stent Selection During the Study Period BES = biolimus-eluting stent(s) (Nobori, Terumo Corporation, Tokyo, Japan); BMS = bare-metal stent(s); DES = drug-eluting stent(s); EES = everolimus-eluting stent(s) (either PROMUS, Boston Scientific Corp., Natick, Massachusetts, or XIENCE-V, Abbott Vascular Devices, Santa Clara, California); SES = sirolimus-eluting stent(s) (Cypher, Cordis, Johnson & Johnson Company, Warren, New Jersey); PES = paclitaxel-eluting stent(s) (including Taxus, Boston Scientific Corp.; CoStar, Conor Medsystems, Menlo Park, California; and Infinnium, Sahajanad Medical Technologies, India); ZES = zotarolimus-eluting stent(s) (Endeavor and Endeavor Resolute, Medtronic, Santa Rosa, California).

Data collection, end points, and definitions.   Clinical follow-up was performed by telephone contact or office visit at 1, 6, and 12 months after the index procedure. The clinical end points analyzed were periprocedural MI, death, after-discharge MI, stent thrombosis (ST), target vessel revascularization (TVR), target lesion revascularization (TLR), and major adverse cardiac events (MACE). The MACE was defined, as it was in the SPIRIT trials (2–5,13), as a composite of cardiac death, MI, and TLR during the follow-up period, which were evaluated on a per-patient basis. We also analyzed TLR separately on a per-lesion basis. All deaths were considered cardiac unless otherwise documented. We defined post-procedural non–Q-wave MI as a creatinine kinase-myocardial band elevation of >3 times the upper limit of normal (14). Creatinine kinase was routinely measured after percutaneous coronary intervention in all patients at both centers. Non-procedural or after-discharge MI was defined as an elevation of troponin above the upper range limit in combination with at least 1 of the following: symptoms of ischemia, electrocardiography changes indicative of new ischemia, or the development of pathological Q waves on electrocardiography (14,15). We defined TLR as repeat revascularization within the stent or within the 5-mm borders proximal or distal to the stent edge at the follow-up angiogram. The TLR was considered to be ischemic-driven if associated with a positive functional study result and/or ischemic symptoms and a target lesion diameter stenosis of 50% by visual estimation or a target lesion diameter stenosis of 70% with or without documented ischemia (2). These are exactly the same criteria used in the SPIRIT trials (2–5,13). We defined TVR as any repeat revascularization of the target vessel. The ST was defined as "acute" if within 24 h of the procedure, "subacute" at 1 to 30 days, and "late" after 30 days. The definition of ST was in accordance with the Academic Research Committee definitions of definite, probable, possible ST (15). In this study we also analyzed the outcomes of EES when implanted for "on-label" and "off-label" (or untested) indications. For the purpose of this study, an off-label indication was defined as implantation of an EES in: 1) left main coronary artery lesions; 2) chronic total occlusions; 3) bifurcation lesions (i.e., main vessel treated by stent implantation and side branch treated by angioplasty or stent implantation); 4) BMS or DES restenosis; 5) bypass graft lesions; 6) left ventricular ejection fraction 35%; 7) ostial lesions (either aorto-ostial or ostium of left anterior descending or circumflex arteries); and 8) diffuse disease defined as 2 or more overlapping stents with stented length >28 mm.

Statistical methods.   Continuous variables are presented as mean ± SD or median with interquartile ranges, and categorical variables are presented as frequencies. The normality of the distribution of the continuous variables was tested by the Kolmogorov-Smirnov goodness-of-fit test. Continuous variables were compared with independent sample Student t or Mann-Whitney U test. Categorical variables were compared with chi-square statistic or Fisher exact test when appropriate. Patients lost to follow-up in whom no event had occurred before the follow-up windows were not included in the denominator for calculations of binary end points. We calculated 95% confidence intervals (CIs) for proportions by the Wilson method and the relative risk by the exact method. Exploratory multivariable analysis was performed to assess the impact of off-label EES usage on the risk of MACE and TLR by logistic regression. The final model included variables associated at univariate analysis with MACE and TLR (all with a p value < 0.1). The results are reported as adjusted odds ratios (ORs) with associated 95% CI. Goodness of fit of the logistic regression model was assessed with the Hosmer-Lemeshow statistic. Survival curves with all available follow-up data were also constructed for time-to-event variables with Kaplan-Meier estimates. A p value < 0.05 was considered statistically significant, and all reported p values are 2-sided. Statistical analysis was performed with SPSS software (version 11.5, SPSS Inc., Chicago, Illinois) and Confidence Interval Analysis.

	Results

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A total of 345 patients and 573 lesions were treated with EES during the study period. The baseline clinical and lesion characteristics of the study population are summarized in Table 1. According to the study definitions, EES were implanted for an off-label indication in 337 (66.1%) lesions, with 248 (71.9%) patients having 1 or more off-label lesion treated. The indications for off-label EES use are listed in Table 1. Clinical follow-up was available in 341 (98.8%) patients with a median follow-up time of 378 days (interquartile range 334 to 473). The duration of clinical follow-up was not statistically different between the 2 groups (p = 0.41).

View larger version (12K): [in this window] [in a new window] [Download PPT slide]   Figure 2 Time-to-Event Curves for MACE Up to 1 Year Time-to-event curves for major adverse cardiac events (MACE) up to 1 year among patients undergoing everolimus-eluting stent implantation for on-label and off-label indications. Event rates presented here were calculated by Kaplan-Meier methods and compared with the log-rank test and differ slightly from those in the results and Table 4, which were calculated as categorical variables and compared with the Fisher exact test. The number of patients at risk for each follow-up period is given below each graph. HR = hazard ratio.

At the last clinical follow-up contact, 3.8% (13) of patients had prematurely discontinued dual antiplatelet therapy before the prescribed 12 months. There were no differences in the rates of ST between the groups. In the total study population, there were 3 (0.9%) cases of definite ST (2 late, and 1 subacute), no probable ST, and 8 cases of possible ST due to unexplained death after 30 days. All 3 cases of definite ST occurred in patients still taking dual antiplatelet therapy, and all of them survived the thrombotic event. There were 2 cases of definite ST in the off-label group. The first was a late ST at 262 days in an 82-year-old man with a normal ejection fraction. He had undergone percutaneous coronary intervention of an ostial left anterior descending artery lesion with a cross-over technique and implantation of a 3.5 x 23 mm EES from the distal left main to the left anterior descending artery, a provisional approach to the circumflex, and final kissing inflation to the bifurcation. He presented with a non–ST-segment elevation MI; angiography demonstrated thrombus intrastent in the distal left main involving the ostia of the circumflex and left anterior descending arteries. He was treated with intravenous glycoprotein IIb/IIIa inhibitors, balloon angioplasty, and BMS implantation. The second definite ST in the off-label group was in a 77-year-old woman with a normal ejection fraction and diabetes treated with insulin. In the index procedure, she underwent stenting of an ostial circumflex lesion with a 3.5 x 12 mm EES. She presented 27 days later with a subacute ST and acute MI that was treated with repeat BMS implantation. The only case of definite ST in the on-label group occurred in a 62-year-old man who presented at 73 days with a late ST after having a mid-circumflex lesion treated with a 3 x 23 mm EES. He underwent primary angioplasty with repeat DES implantation at another institution.

	Discussion

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The main findings of this real-world registry are: 1) in unrestricted daily practice, EES were implanted predominantly for off-label indications and were associated with a relatively low rate of ischemic-driven TLR and MACE during short- and medium-term follow-up; 2) although MACE and TLR in this complex cohort were slightly higher than those seen in the SPIRIT randomized trials (2–6), the results of on-label use were comparable; 3) the rates of cardiac death, MI, and ST were not statistically different for on-label and off-label EES implantation; 4) on multivariable analysis, previous bypass surgery and diabetes were associated with MACE and diabetes also with TLR, but off-label EES implantation was not a risk factor for either MACE or TLR; and 5) even though TLR was twice as frequent in off-label patients, it did not reach statistical significance.

In this study the majority of patients had an off-label lesion treated with an EES—contrary to most randomized trials—with one-half of the off-label patients having more than 1 off-label lesion treated. However, despite this increased complexity of the patients and lesions treated, the cumulative 10.6% MACE and 7.9% TLR rates in this study were not markedly different from the 12-month rates in the SPIRIT III trial of 6.0% and 3.8% (2). In fact, when on-label lesions such as those enrolled in the SPIRIT III trial were considered, the rates of MACE (6.3% vs. 6.0%) and TLR (4.2% vs. 3.8%) were almost identical. The question of whether off-label DES implantation is associated with worse outcomes in particular with regard to hard end points such as death and MI has been an area of great concern for patients, care-givers, and health authorities (1,7,8,16–19). Thus we performed a comparison of EES implanted for on-label (i.e., Food and Drug Administration-approved) indications with off-label and untested usage. Considering the complexity of the lesions in the off-label group (e.g., left main, diffuse disease, chronic total occlusions, and bifurcations), the procedures performed were more complex with more and longer stents implanted, increased intra-aortic balloon pump support, and greater IVUS use. We should also point out that the finding of a larger reference vessel diameter in the off-label group, although seemingly counterintuitive, is most likely due to percutaneous coronary intervention on vessels with a larger vessel diameter, such as the left main and saphenous vein grafts. Indeed, when we excluded these lesions, the reference vessel diameter was similar between the on-label and off-label groups (2.60 ± 0.52 mm vs. 2.69 ± 0.61 mm, p = 0.13). The factors that probably contribute most to the larger acute gain in the off-label group were the inclusion of chronic total occlusions; the slightly higher use of IVUS; and that many off-label lesions were in the context of more diffuse coronary disease, a situation where the mismatch between angiography and IVUS vessel size is larger compared with more simple lesions. This situation will give more advantage in terms of acute gain when IVUS is used in off-label compared with on-label lesions. Despite the increased complexity of the patients, lesions treated, and interventional procedure, the rate of in-hospital adverse events was not statistically different between the 2 groups, but there were numerically more periprocedural MI. The cumulative TLR rate, which was numerically higher in the off-label group (9.3% vs. 4.2%), can be explained by the fact that these patients had a greater number of lesions treated and most of these were complex, justifying a higher rate of re-intervention (20). That these differences were not statistically significant is likely a consequence of the overall insufficient number of patients evaluated. Furthermore, we believe that the TLR rate in this complex cohort is realistic, considering that we do not currently perform routine angiographic follow-up, which occurred only in 45% of patients.

Because the off-label indications are known to form a group at high risk of restenosis that might have greater benefit from DES, a higher TLR rate might be acceptable, especially because the rates of death and MI were not statistically higher. Furthermore, off-label EES usage was not associated with MACE on multivariable analysis, suggesting that the implantation of EES in off-label lesions might be acceptable and without incremental risk.

It has been proposed that EES might have a theoretical advantage over first-generation DES with regard to safety, in that the thin strut design might result in more rapid stent endothelialization (13,21). Indeed the rate of ST is much less than we previously reported with the first-generation DES (7). Furthermore, the 0.9% rate of definite and probable ST in this study of complex lesions is very similar to that reported in on-labels lesions at 12 months in the SPIRIT III trial (1.1%) (2). The low rate of ST might be explained by the high compliance and extended duration of dual antiplatelet therapy. However, it is reassuring that off-label EES implantation was not associated with a higher risk of ST.

Study limitations.   This study suffers the obvious limitations of observational nonrandomized registries. However, it does provide important complementary information about the outcomes in real-world patients and lesions that were excluded from the randomized trials. The study is underpowered to permit any strong conclusions to be drawn from the subgroup analyses, which should be considered hypothesis-generating. Furthermore, the small number of events limits the ability to control for all differences among the subgroups without some over-fitting of the multivariable model. Similarly, the relatively small overall sample size prohibits any judgment to be made with regard to ST as a safety parameter, because this is a very rare event. Longer-term follow-up is required, because the incremental risk of ST with DES might emerge beyond 1 year (22). However, in the SPIRIT III trial, there were fewer ST events after 1 year in patients treated with EES rather than paclitaxel-eluting stents (13). The lack of routine angiographic follow-up precludes any comments about the antirestenotic efficacy of EES in complex lesions. However, in this clinical study all TLR was ischemic-driven, and thus the effect of an overzealous oculostenotic reflex might be limited. Despite these shortcomings, these initial observations do provide an important insight into the clinical spectrum and clinical outcomes of patients and lesions currently being treated with this second-generation DES.

	Conclusions

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In unrestricted daily practice, EES were implanted predominantly for off-label and untested indications and associated with a relatively low rate of MACE and ischemic-driven TLR. However, longer-term data are needed to assess the safety of this new platform in complex lesions.

	Footnotes

 
Azeem Latib and Dr. Ferri contributed equally to the manuscript and are joint first authors.

^_* Reprint requests and correspondence: Dr. Antonio Colombo, EMO-GVM Centro Cuore Columbus, 48 Via M. Buonarroti, 20145 Milan, Italy (Email: info{at}emocolumbus.it).

Manuscript received June 19, 2009; revised manuscript received August 27, 2009, accepted September 20, 2009.

	REFERENCES

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1. Torguson R, Waksman R. Overview of the 2007 Food and Drug Administration Circulatory System Devices Panel meeting on the Xience V Everolimus-Eluting Coronary Stent Am J Cardiol 2008;102:1624-1630.[CrossRef][Web of Science][Medline]
2. Stone GW, Midei M, Newman W, et al. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial JAMA 2008;299:1903-1913.[Abstract/Free Full Text]
3. Ruygrok PN, Desaga M, Van Den Branden F, et al. One year clinical follow-up of the XIENCE-V everolimus-eluting stent system in the treatment of patients with de novo native coronary artery lesions: the SPIRIT II study EuroIntervention 2007;3:315-320.[Medline]
4. Serruys PW, Ong A, Piek JJ, et al. A randomized comparison of a durable polymer everolimus-eluting stent with a bare metal coronary stent: the SPIRIT first trial EuroIntervention 2005;1:58-65.[Medline]
5. Serruys PW, Ruygrok PN, Neuzner J, et al. A randomised comparison of an everolimus-eluting coronary stent with a paclitaxel-eluting coronary stent: the SPIRIT II trial EuroIntervention 2006;2:286-294.[Medline]
6. Tsuchida K, Piek JJ, Neumann FJ, et al. One-year results of a durable polymer everolimus-eluting stent in de novo coronary narrowings (the SPIRIT FIRST Trial) EuroIntervention 2005;1:266-272.[Medline]
7. Qasim A, Cosgrave J, Latib A, Colombo A. Long-term follow-up of drug-eluting stents when inserted for on- and off-label indications Am J Cardiol 2007;100:1619-1624.[CrossRef][Web of Science][Medline]
8. Roy P, Buch AN, Javaid A, et al. Impact of "off-label" utilization of drug-eluting stents on clinical outcomes in patients undergoing percutaneous coronary intervention Am J Cardiol 2008;101:293-299.[CrossRef][Web of Science][Medline]
9. Airoldi F, Colombo A, Morici N, et al. Incidence and predictors of drug-eluting stents thrombosis during and after discontinuation of thienopyridine treatment Circulation 2007;116:745-754.[Abstract/Free Full Text]
10. Cosgrave J, Melzi G, Corbett S, et al. Comparable clinical outcomes with paclitaxel- and sirolimus-eluting stents in unrestricted contemporary practice J Am Coll Cardiol 2007;49:2320-2328.[Abstract/Free Full Text]
11. Cosgrave J, Agostoni P, Ge L, et al. Clinical outcome following aleatory implantation of paclitaxel-eluting or sirolimus-eluting stents in complex coronary lesions Am J Cardiol 2005;96:1663-1668.[CrossRef][Web of Science][Medline]
12. Lemos PA, Serruys PW, van Domburg RT, et al. Unrestricted utilization of sirolimus-eluting stents compared with conventional bare stent implantation in the "real world": the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry Circulation 2004;109:190-195.[Abstract/Free Full Text]
13. Stone GW, Midei M, Newman W, et al. 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.[Abstract/Free Full Text]
14. Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction Circulation 2007;116:2634-2653.[Free Full Text]
15. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions Circulation 2007;115:2344-2351.[Abstract/Free Full Text]
16. Applegate RJ, Sacrinty MT, Kutcher MA, et al. "Off-label" stent therapy 2-year comparison of drug-eluting versus bare-metal stents J Am Coll Cardiol 2008;51:607-614.[Abstract/Free Full Text]
17. Beohar N, Davidson CJ, Kip KE, et al. Outcomes and complications associated with off-label and untested use of drug-eluting stents JAMA 2007;297:1992-2000.[Abstract/Free Full Text]
18. Grines CL. Off-label use of drug-eluting stents putting it in perspective J Am Coll Cardiol 2008;51:615-617.[Free Full Text]
19. Marroquin OC, Selzer F, Mulukutla SR, et al. A comparison of bare-metal and drug-eluting stents for off-label indications N Engl J Med 2008;358:342-352.[CrossRef][Medline]
20. Serruys PW, Morice MC, Kappetein AP, et al. SYNTAX Investigators Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease N Engl J Med 2009;360:961-972.[CrossRef][Medline]
21. Joner M, Nakazawa G, Finn AV, et al. Endothelial cell recovery between comparator polymer-based drug-eluting stents J Am Coll Cardiol 2008;52:333-342.[Abstract/Free Full Text]
22. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents N Engl J Med 2007;356:998-1008.[CrossRef][Medline]

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