Two-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions: The SPIRIT II Trial

Abstract

HomeCirculation: Cardiovascular InterventionsVol. 2, No. 4Two-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery Lesions Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessResearch ArticlePDF/EPUBTwo-Year Clinical, Angiographic, and Intravascular Ultrasound Follow-Up of the XIENCE V Everolimus-Eluting Stent in the Treatment of Patients With De Novo Native Coronary Artery LesionsThe SPIRIT II Trial Bimmer E. Claessen, MD, Marcel A. Beijk, MD, Victor Legrand, MD, Witold Ruzyllo, MD, Antonio Manari, MD, Olivier Varenne, MD, PhD, Maarten J. Suttorp, MD, PhD, Jan G.P. Tijssen, PhD, Karine Miquel-Hebert, PhD, Susan Veldhof, RN, Jose P.S. Henriques, MD, PhD, Patrick W. Serruys, MD, PhD and Jan J. Piek, MD, PhD Bimmer E. ClaessenBimmer E. Claessen From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Marcel A. BeijkMarcel A. Beijk From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Victor LegrandVictor Legrand From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Witold RuzylloWitold Ruzyllo From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Antonio ManariAntonio Manari From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Olivier VarenneOlivier Varenne From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Maarten J. SuttorpMaarten J. Suttorp From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Jan G.P. TijssenJan G.P. Tijssen From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Karine Miquel-HebertKarine Miquel-Hebert From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Susan VeldhofSusan Veldhof From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Jose P.S. HenriquesJose P.S. Henriques From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author , Patrick W. SerruysPatrick W. Serruys From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author and Jan J. PiekJan J. Piek From the Department of Cardiology (B.E.C., M.A.B., J.G.P.T., J.P.S.H., J.J.P.), Academic Medical Center, University of Amsterdam, The Netherlands; C.H.U. de Liege Sart Tilman (V.L.), Liege, Belgium; National Institute of Cardiology in Warsaw (W.R.), Warsaw, Poland; Azienda Ospedaliera Santa Maria Nuova (A.M.), Reggio Emilia, Italy; Hopital Cochin (O.V.), Paris, France; St. Antonius Ziekenhuis (M.J.S.), Nieuwegein, The Netherlands; Abbott Vascular (K.M.-H., S.V.), Diegem, Belgium; and Thoraxcenter (P.W.S.), Erasmus Medical Center, Rotterdam, The Netherlands. Search for more papers by this author Originally published22 Jul 2009https://doi.org/10.1161/CIRCINTERVENTIONS.108.831800.108.831800Circulation: Cardiovascular Interventions. 2009;2:339–347Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2009: Previous Version 1 AbstractBackground— This article reports the 2-year clinical, angiographic, and intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial.Methods and Results— This was a prospective, single-blind clinical trial in which a total of 300 patients with de novo native coronary artery lesions were randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned at 2 years in all patients. A subset of 152 patients underwent serial angiographic and intravascular ultrasound analyses at 6 months and 2 years. After 2 years, target lesion failure (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES and PES, respectively (P=0.31). At 6 months, a significant reduction in angiographic in-stent late loss and percentage volume obstruction measured by intravascular ultrasound was observed in the EES group. However, at 2-year follow-up, a late increased intimal hyperplasia growth after implantation of an EES was observed. There were no significant differences between EES and PES for in-stent late loss (EES, 0.33�0.37 mm versus PES, 0.34�0.34 mm; P=0.84) and percentage volume obstruction (EES, 5.18�6.22% versus PES, 5.80�6.31%; P=0.65) at 2 years. The incidence of stent thrombosis was low and comparable in both groups (EES, 0.9%; PES, 1.4%).Conclusions— Although the previously reported angiographic and clinical superiority of the EES has vanished over time, this report confirms and extends the previously demonstrated noninferiority in terms of in-stent late loss of the EES when compared with the PES up to 2-year follow-up. There were no significant differences between EES and PES in clinical, angiographic and intravascular ultrasound outcomes at 2 years.Stenting of de novo lesions in native coronary arteries is an established and effective treatment of coronary narrowing due to atherosclerosis. However, long-term efficacy of bare metal stents (BMS) has been hampered by the development of restenosis, resulting in rehospitalization for percutaneous or surgical revascularization in 10% to 20% of patients.1 Drug-eluting stents (DES) have been shown to be effective against restenosis by reducing neointimal hyperplasia after vascular injury, when compared with BMS.2Clinical Perspective on p 339The objective of the SPIRIT II trial was to evaluate the safety and performance of the everolimus-eluting coronary stent (XIENCE V, Abbott Vascular, Santa Clara, Calif) compared with the paclitaxel-eluting coronary stent (TAXUS EXPRESS2 or Liberte, Boston Scientific, Natick, Mass) in the treatment of de novo native coronary artery lesions. The everolimus-eluting stent (EES) is comprised of the ACS MULTI-LINK VISION stent and delivery system and a drug-eluting coating. Everolimus, an analogue of rapamycin, is a powerful antiproliferative agent that blocks cell cycle progression between the G1 and S phases, inhibiting smooth muscle cell proliferation.3 The feasibility of the EES was first demonstrated in the FUTURE-I and FUTURE II studies and more recently in the SPIRIT FIRST study, which demonstrated both clinical safety and efficacy.4–7 In the SPIRIT FIRST study, the clinical outcome at 2-year follow-up was in favor of the EES group compared with the BMS group but did not reach statistical significance because of small patient numbers.In this trial, the EES performed superior to the paclitaxel-eluting stent (PES) regarding angiographic late loss at 6 months (0.11�0.27 versus 0.36�0.39 mm). Furthermore, intravascular ultrasound (IVUS) results showed that the EES was more effective at reducing neointimal hyperplasia; both percentage volume obstruction and neointimal hyperplasia volume were significantly lower in patients treated with EES.8 The incidence of target lesion failure (TLF) was low and comparable between groups at 6 months (2.7% for EES versus 6.5% for PES). At 1 year, there was a significant benefit in TLF favoring the EES (2.7% versus 9.2%).9This report focuses on the 2-year clinical outcomes of all patients enrolled in the SPIRIT II trial and the angiographic and IVUS follow-up in a subset of patients.MethodsStudy PopulationThe study design of the SPIRIT II trial has been previously described.8–10 In brief, this prospective, randomized (3:1) single-blind, parallel 2-arm trial was performed at 28 centers in Europe, India, and New Zealand and randomized 300 patients in a 3:1 ratio to either an EES (n=223) or a PES (n=77) between July 2005 and November 2005. The study protocol was approved by the ethics committee at each participating institution, and all patients gave written informed consent.Patients enrolled in the study were older than 18 years with evidence of myocardial ischemia and had a maximum of 2 de novo native coronary artery lesions, located in different major epicardial vessels. Target lesions had to comply with the following inclusion criteria: a reference vessel diameter between 2.5 and 4.25 mm by visual estimation, a target lesion length ≤28 mm, a visually estimated stenosis between 50% and 99% of the luminal diameter, and a Thrombolysis In Myocardial Infarction flow grade of 1 or more. Patients were excluded from enrollment if they had documented acute myocardial infarction within 3 days prior to the baseline procedure, a left ventricular ejection fraction <30%, were awaiting a heart transplant or had a known hypersensitivity or contraindication to aspirin, heparin, bivalirudin, clopidogrel or ticlopidine, cobalt, chromium, nickel, tungsten, everolimus, paclitaxel, acrylic, and fluoropolymers. Angiographic exclusion criteria were target lesions within 2 mm of the origin of the left anterior descending or left circumflex coronary artery, heavy calcification, or a visible thrombus within the target vessel.Study ProcedureFollowing the confirmation of angiographic in- and exclusion criteria before the procedure, patients were randomized through a telephone call to either an EES or a PES. Because of packaging differences, operators were not blinded to the device. Lesions were treated using standard interventional techniques with mandatory predilatation and stent implantation pressure not exceeding the burst pressure rate. Postdilatation was left to the discretion of the physician, and if performed was only to be done with balloons sized to fit within the boundaries of the stent. In the event of a bailout procedure and additional stent requirement, the stent had to be one from the same group as the first implanted stent. At baseline, IVUS was performed in a subset of 152 consecutive patients enrolled in preselected centers, after angiographically optimal stent placement had been obtained. IVUS was repeated if additional postdilatation was performed to optimize stent apposition and/or deployment. Patient preparation and pharmaceutical treatment during the hospital procedure were to be in accordance with standard hospital practice. The use of GPIIb/IIIa inhibitors was left to the discretion of the physician. All patients were to receive 75 mg of clopidogrel for a minimum of 6 months and ≥75 mg of aspirin daily for a minimum of 1 year after the procedure.Follow-UpClinical follow-up was scheduled at 30, 180, and 270 days and 1 and 2 years with further evaluations planned at 3, 4, and 5 years by protocol amendment. At outpatient visits, patients were asked specific questions about the interim development of angina or the occurrence of adverse events. Angiographic follow-up was planned at 180 days for all patients. In the subset of 152 consecutive patients (enrolled in selected centers), IVUS was planned at 180 days and both IVUS and angiographic follow-up were to be repeated at 2 years. There was a 28-day window for the visit at 2 years.Clinical End PointsThe clinical part of this 2-year follow-up study focuses on TLF (cardiac death, myocardial infarction [MI], and ischemia-driven target lesion revascularization [TLR], either by coronary artery bypass graft or percutaneous coronary intervention—defined as major adverse cardiac events in the study protocol). Secondary clinical end points included target vessel failure (cardiac death, MI, and ischemia-driven target vessel revascularization), TLR, target vessel revascularization, and stent thrombosis. All clinical end points were adjudicated by a blinded clinical events committee.All deaths that could not be clearly attributed to a noncardiac cause were considered cardiac deaths. Q-Wave MI was defined as development of new pathological Q waves. Non–Q-wave MI was defined as a typical rise and fall of creatine kinase-MB with at least one of the following: ischemic symptoms, electrocardiographic changes indicative of ischemia, or associated with a coronary artery intervention. For nonprocedural/spontaneous MI, creatine kinase-MB had to be ≥2 times the upper limit of normal, for postpercutaneous coronary intervention ≥3 times upper limit of normal, and for postcoronary artery bypass grafting ≥5 times the upper limit of normal. For each MI, the relationship to the target vessel was adjudicated by the clinical events committee.Ischemia-driven TLR was defined as a revascularization at the target lesion associated with any of the following: a positive functional ischemia study (exercise testing, fractional flow reserve, or coronary flow reserve), ischemic symptoms, and an angiographic diameter stenosis ≥50% by core laboratory quantitative coronary angiography (QCA); or a diameter stenosis ≥70% by core laboratory QCA without ischemic symptoms or a positive functional study.Stent thrombosis was categorized according to the definitions proposed by the Academic Research Consortium for definite, probable, and possible stent thrombosis.11Angiographic End PointsThe angiographic part of this article focuses on in-stent late loss at 2 years (in the subset of 152 patients). Secondary angiographic end points include in-segment late loss, proximal and distal late loss, in-stent and in-segment percentage diameter stenosis, and angiographic binary restenosis.QCA was performed using the CAAS II analysis system (Pie Medical BV, Maastricht, The Netherlands) by an independent core laboratory (Cardialysis BV, Rotterdam, The Netherlands) with observers blinded to treatment assignment. In each patient, the stented segment and the peri-stent segments (defined by a length of 5 mm proximal and distal to the stent edge) were analyzed. The following QCA parameters were computed: minimal luminal diameter, reference vessel diameter obtained by an interpolated method, and percentage diameter stenosis. Binary restenosis was defined in every segment as a diameter stenosis ≥50% at follow-up. Late loss was defined as the difference between minimal luminal diameter postprocedure and minimal luminal diameter at follow-up. If a patient underwent TLR before the scheduled 2-year angiography, QCA was performed on the preinterventional angiography, and its results were imputed into 2-year follow-up angiography outcomes.IVUS End PointsThe IVUS part of this article focuses on percentage in-stent volume obstruction at 2 years (in the subset of 152 patients). Secondary IVUS end points include in-stent neointimal volume and vessel, stent, and lumen volumes.Postprocedure and follow-up stented vessel segments were examined with mechanical or phased array IVUS (Eagle-eye Volcano, Rancho Cordova, Calif; Atlantis, Boston Scientific, Natick, Mass) using automated pull-back at 0.5 mm per second after administration of 0.2 mg intracoronary nitroglycerin. The coronary segment beginning 5-mm distal to and extending 5-mm proximal to the stented segment was examined. IVUS analyses were also performed by an independent core laboratory (Cardialysis BV, Rotterdam, The Netherlands) with observers blinded to treatment assignment. A computer-based contour detection program was used for automated 3D reconstruction of the stented and adjacent segments. The lumen, stent boundaries, and external elastic membrane (vessel boundaries) were detected using a minimum cost algorithm.12 The stent volume and lumen volume were calculated according to Simpson’s rule.13 The in-stent neointimal volume was calculated as the difference between stent volume and lumen volume. The percentage obstruction of the stent volume was calculated as intrastent neointimal volume/stent volume�100. Feasibility, reproducibility, and inter- and intra-observer variability of this system have been validated in vitro and in vivo.13 Incomplete apposition was defined as one or more stent struts separated from the vessel wall with evidence of blood speckles behind the strut on ultrasound, whereas late-acquired incomplete apposition was defined as incomplete apposition of the stent at follow-up which was not present postprocedure.14–16Statistical MethodsFinal 2-year results are presented in this article. Six-month results in patients whose 2-year results were available are presented for comparative purposes. (These results may differ from those in previous publications with more patients) Binary variables are presented as percentages and compared using the Fisher exact test. Continuous variables are presented as mean�standard deviation and compared using the Student t test. Confidence intervals for the differences are based on normal assumption. Noninferiority probability values for in-stent late-loss in the subset of lesions with serial 6 months and 2 years measurements are calculated with a 1-sided asymptotic test and were not predefined in the protocol. The noninferiority margin used for those tests is 0.16 mm, corresponding to the prespecified margin for the primary end point analysis.8 Survival curves using all available follow-up data were also constructed for time-to-event variables using Kaplan–Meier estimates and compared by log-rank test. Data on patients who were lost to follow-up were censored at the time of the last contact. Data on patients who died of noncardiac causes were censored at the time of death. Statistical analyses were performed using SAS version 9.1.3 (SAS Institute Inc, Cary, NC).ResultsPatients and EnrollmentTwo-year clinical follow-up was available for 211 of the 223 patients (94.6%) in the EES group and in 73 of the 77 patients (94.8%) of the PES group (Figure 1). In the EES group, 4 patients withdrew, 1 patient was lost to follow-up, and 7 patients died from a noncardiac cause. In the PES group with no patients lost to follow-up, 4 patients died from a noncardiac cause. Baseline demographic, clinical, and angiographic characteristics of the treatment groups have previously been reported and are summarized in Table 1.8 There were no significant differences between treatment groups in any of the tabulated characteristics, with the exception of a smaller minimal lumen diameter (MLD) in the EES group (P=0.03). Of the subset of 152 patients in the angiography and IVUS subgroup, a further subset of 115 patients underwent serial and analyzable angiography (EES, 97 lesions, 83 patients, 73%; PES, 35 lesions, 32 patients, 82%) and 95 patients underwent serial and analyzable IVUS (EES, 69 lesions, 64 patients, 57%; PES, 32 lesions, 31 patients, 79%). The angiography and IVUS patient subgroup was comparable with the total cohort (data not shown). There were no differences in baseline characteristics between the EES and PES patient groups in the angiography and IVUS subset of patients with the exception of a higher prevalence of previous MI in the EES patient group (EES: 42%; PES: 18%, P<0.01) and a smaller MLD in the EES group (P=0.01). Download figureDownload PowerPointFigure 1. Patient flow chart and clinical, angiographic, and intravascular ultrasound follow-up in the SPIRIT II trial.Table 1. Baseline CharacteristicsEES (n=223)PES (n=77)There were no significant differences in baseline variables between the groups, with the exception of a smaller MLD in the EES group (P=0.03).Patient characteristics, % (unless otherwise specified) Age (mean�SD), y62�1062�9 Men7179 Hypertension-requiring medication6765 Hypercholesterolemia-requiring medication6975 Diabetes mellitus2324 Current smoker3230 Prior myocardial infarction3525 Unstable angina2732Target vessel, %NL=260NL=91 Left anterior descending4147 Left circumflex2919 Right coronary artery3034Target lesion characteristics, mean�SD Reference vessel diameter, mm2.70�0.522.82�0.58 Minimal lumen diameter, mm1.06�0.421.14�0.36 Diameter stenosis, %61�1259�10 Lesion length, mm13.0�5.713.2�6.4Clinical OutcomesTable 2 shows target vessel failure (TLF) at 2 years and each of its components. At 2 years, TLF occurred in 6.6% of the EES group compared with 11.0% in the PES group. In each treatment group, 1 patient died of a cardiac cause (0.5% versus 1.4%). The incidence of MI at 2 years was 2.8% (6 patients) and 5.5% (4 patients) in the EES and PES groups, respectively. Ischemia-driven TLR comprised the majority of TLF within both groups with 3.8% (8 patients) and 6.8% (5 patients) in the EES and PES groups, respectively. The temporal distribution of TLF and its component events is shown in Kaplan–Meier curves (Figure 2). Although TLF rates in the EES group are consistently lower, the significant separation in TLF rate observed at 1 year was not maintained at the 2-year follow-up (Plogrank=0.223). Table 2. Clinical Outcome at 2 YearsEES (n=211), %PES (n=73), %PP values were calculated using Fisher exact test. Denominators for TVF components and any repeat revascularization are 211 for EES and 73 for PES; denominators for other non-TVF components are 218 for EES and 77 for PES. ID indicates ischemia driven; TVF, target vessel failure.*Hierarchical.Death3.76.50.33Cardiac death0.51.40.45MI related to target vessel2.84.10.7 Q-wave00NA Non–Q-wave2.84.10.70Any MI2.85.50.29 Q-wave00NA Non–Q-wave2.85.50.29Composite of cardiac death or MI*3.35.50.48ID TLR3.86.80.33 Percutaneous3.86.80.33 Surgical00NATLF*6.611.00.31Any TLR4.69.10.16 Percutaneous4.69.10.16 Surgical00NAID target vessel revascularization7.19.60.46 Percutaneous6.69.60.44 Surgical0.501.00TVF*10.012.30.66Any target vessel revascularization8.711.70.50 Percutaneous7.811.70.35 Surgical0.90.01.00Any repeat revascularization15.615.11.00Download figureDownload PowerPointFigure 2. Cumulative distribution curves for 2-year and 180-day in-stent late loss. The probability value for noninferiority of the EES at 2 years was 0.005 (non prespecified analysis in this subgroup).Definite or probable stent thrombosis occurred once in 2 patients (0.9%) in the EES treatment group and twice in one patient (1.4%) in the PES treatment group. Both the stent thromboses in the everolimus group occurred after 1 year. Characteristics of the stent thrombosis episodes are shown in Table 3. Table 3. Listing of Definite/Probable Stent Thrombosis During 2-Year Follow-UpPatient CharacteristicsPES/EESDayLocationTypeAngiographic ConfirmationMIFatalRepeat RevascularizationLAD indicates left anterior descending; RCA, right coronary artery.55-y-old manPES9Mid LADDefiniteYesNon–Q-waveNoYes55-y-old manPES56Mid LADProbableNoNon–Q-waveYesNo54-y-old manEES538Mid RCADefiniteYesNon–Q-waveNoNo61-y-old manEES721Distal RCAProbableYesNon–Q-waveNoYesAngiographic OutcomesAngiographic results from 132 lesions in the subset of 115 patients who underwent serial angiography at 6 months and 2 years are shown in Table 4. Two-year mean in-stent late loss was 0.33�0.37 mm for the EES group and 0.34�0.34 mm for the PES group (P=0.84) against 0.17�0.32 and 0.33�0.32 (P=0.01) at 6 months. If we would apply the noninferiority margin prespecified for the analysis of the primary end point at 6 months of 0.16 mm, the results at 2 years would still show noninferiority (post hoc analysis).8Figure 3 shows the cumulative distribution frequency curve of in-stent late loss at 6-month and 2-year follow-up. Proximal and distal mean late loss were 0.24�0.49 and 0.08�0.38, respectively, for EES and 0.33�0.45 and 0.11�0.40 for PES. Mean in-stent percent diameter stenosis was 19.21�14 in the everolimus group compared with 18.76�11 in the paclitaxel group (P=0.85). Two-year in-stent angiographic binary restenosis rate was 2.1% for EES and 2.9% for PES (P=1.00