Author + information
- Received August 2, 2012
- Revision received May 15, 2013
- Accepted May 24, 2013
- Published online October 1, 2013.
- Flavio Ribichini, MD∗∗ (, )
- Michele Romano, MD†,
- Renato Rosiello, MD†,
- Luigi La Vecchia, MD‡,
- Ester Cabianca, MD‡,
- Giuseppe Caramanno, MD§,
- Diego Milazzo, MD§,
- Paolo Loschiavo, MD‖,
- Stefano Rigattieri, MD‖,
- Salvatore Musarò, MD¶,
- Bruno Pironi, MD¶,
- Antonio Fiscella, MD#,
- Francesco Amico, MD#,
- Ciro Indolfi, MD∗∗,††,
- Carmen Spaccarotella, MD∗∗,
- Antonio Bartorelli, MD††,
- Daniela Trabattoni, MD††,
- Francesco Della Rovere, MD‡‡,
- Andrea Rolandi, MD‡‡,
- Federico Beqaraj, MD§§,
- Riccardo Belli, MD§§,
- Pietro Sangiorgio, MD‖‖,
- Rosvaldo Villani, MD¶¶,
- Andrea Berni, MD##,
- Imad Sheiban, MD∗∗∗,
- Maria Josè Lopera Quijada, MSC†††,
- Barbara Cappi, MSC†††,
- Licia Ribaldi, BS†††,
- Corrado Vassanelli, MD∗,
- EXECUTIVE Trial Investigators
- ∗Department of Medicine, Università di Verona, Verona, Italy
- †Azienda Ospedaliera Carlo Poma, Mantova, Italy
- ‡Ospedale san Bortolo, Vicenza, Italy
- §Azienda Ospedaliera San Giovanni di Dio, Agrigento, Italy
- ‖Ospedale Sandro Pertini, Roma, Italy
- ¶Ospedale Generale Madre Vannini, Roma, Italy
- #Azienda Ospedaliera Cannizzaro, Catania, Italy
- ∗∗Azienda Ospedaliera Mater Domini Università degli Studi Magna Graecia, Catanzaro, Italy
- ††IRCCS Centro Cardiologico Monzino, Milano, Italy
- ‡‡Ente Ospedaliero Ospedali Galliera, Genova, Italy
- §§Ospedale Maria Vittoria, Torino, Italy
- ‖‖Ospedale Maggiore, Bologna, Italy
- ¶¶Azienda Ospedaliera di Pavia e provincia, Ospedale di Vigevano, Vigevano, Italy
- ##Azienda Ospedaliera S. Andrea, Roma, Italy
- ∗∗∗Azienda Ospedaliera Universitaria Molinette San Giovanni Battista, Torino, Italy
- †††Abbott Vascular Knoll-Ravizza S.p.A., Milano, Italy
- ↵∗Reprint requests and correspondence:
Dr. Flavio Ribichini, University of Verona, Piazzale A. Stefani 1, 37126 Verona, Italy.
Objectives This study sought to investigate the efficacy and performance of the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary lesions in patients with 2- to 3-vessel multivessel coronary artery disease (MV-CAD).
Background Drug-eluting stents (DES) have emerged as an alternative to conventional coronary artery bypass surgery in patients with MV-CAD although first-generation DES yielded inferior efficacy and safety compared with surgery.
Methods Prospective, randomized (1:1), multicenter feasibility trial was designed to assess angiographic efficacy of EES compared with the TAXUS paclitaxel-eluting stent (PES) in 200 patients, and a prospective, open-label, single-arm, controlled registry was designed to analyze the clinical outcome of EES at 1-year follow-up in 400 MV-CAD patients. For the randomized trial, the primary endpoint was in-stent late loss at 9 months. For the registry, the primary endpoint was a composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization at 12 months.
Results The primary endpoint per single lesion was significantly lower in the EES group compared with the PES group (−0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed when analyzing all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001). Clinical outcome at 1 year yielded a composite of major adverse cardiac events of 9.2% in the single-arm registry, and 11.1% and 16.5% in the EES and PES randomized groups, respectively (p = 0.30).
Conclusions The EXECUTIVE trial was a randomized pilot trial dedicated to the comparison of the efficacy of 2 different DES among patients with 2- to 3-vessel MV-CAD. The study shows lower in-stent late loss at 9 months with the EES XIENCE V compared with the PES TAXUS Libertè, and a low major adverse cardiac event rate at 1 year in patients with 2-to 3-vessel MV-CAD. (EXECUTIVE [EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease]; NCT00531011)
Progress in medical care and economic and social development result in a continuous increment of life expectancy, and elderly patients are frequently exposed to widespread forms of atherosclerosis. In most cases, patients with multivessel (MV) coronary artery disease (CAD) have diffuse atherosclerosis and complex lesions, are often diabetic, and present with impaired left ventricular function. Initial comparisons between percutaneous coronary intervention (PCI) with bare-metal stents and coronary artery bypass graft surgery had shown a relative equivalence of the 2 treatments in terms of survival, but a clearly higher efficacy of surgery in preventing ischemic recurrences (1–4). Such studies, however, included patients with relatively low angiographic complexity and with 1- or 2-vessel disease in over 40% of cases, and excluded patients with left main lesions or impaired left ventricular function, a selection that clearly reduced the potential benefits of surgery (5). With the advent of drug-eluting stents (DES), results of PCI improved significantly (6,7), but unlike surgery, remained strongly influenced by the severity and extent of the MV-CAD. Such differences was clearly demonstrated in the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial, a real “all-comers study” that randomized patients with 3-vessel disease, including those with left main stenosis, to PCI with DES or to coronary surgery (8,9). Based on such observations, recent guidelines on myocardial revascularization confirm the superiority of coronary bypass surgery over PCI in patients with MV-CAD, in particular in those cases with diffuse disease as expressed by intermediate or high SYNTAX scores, whereas PCI is considered to be an appropriate alternative in patients with limited angiographic complexity (10–12). The recently developed SYNTAX score II (13) has demonstrated the ability to better guide decision making between surgery and PCI than the assessment provided by the anatomic SYNTAX score alone. Current recommendations, however, are based on the results obtained with sirolimus-eluting stents and paclitaxel-eluting stents (PES), both considered to belong to the “first generation” of DES.
More recent investigations have demonstrated significantly better clinical and angiographic outcomes of a new-generation everolimus-eluting stent (EES) compared with PES (14–16). The availability of safer and more effective DES generates the hypothesis that these may reduce the gap between PCI and surgery in patients with MV-CAD. However, despite the myriad of studies performed with DES, patients with advanced MV-CAD have been regularly excluded from comparative PCI trials, and despite the lack of dedicated studies, PCI in patients with MV-CAD has become current practice.
Aim of the study
The EXECUTIVE (EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease) trial (NCT00531011) aims to assess the efficacy and performance of the XIENCE V EES (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary artery lesions in patients with MV-CAD (intended as 2- or 3-vessel disease). Its efficacy in preventing neointimal proliferation 9 months after stent placement as assessed by quantitative coronary angiography (QCA) was also compared with the TAXUS Libertè PES (Boston Scientific, Natick, Massachusetts).
Detailed information regarding the study protocol has been published previously (17). In brief, the EXECUTIVE trial is a prospective, double-arm, randomized multicenter trial comparing the XIENCE V EES to the TAXUS Liberté PES in the treatment of patients with MV-CAD, performed in parallel to a nationwide, prospective, open-label, single-arm registry evaluating the performance of the EES in patients with 2- or 3-vessel MV-CAD treated in daily practice. MV-CAD was defined as in previous recent studies of coronary revascularization by PCI or coronary bypass surgery (1–4,6,7,18). The study was conducted in 30 centers in Italy that enrolled 600 patients in total.
The EXECUTIVE randomized trial enrolled 200 patients fulfilling the eligibility criteria. By randomization, treatment was assigned in a 1:1 ratio to receive EES or PES. In the EXECUTIVE registry, 400 patients with MV-CAD suitable to receive treatment of coronary lesions with multiple EES entered a prospective, controlled registry. The study was approved by the medical ethics committee at each participating center. All patients provided written informed consent before their participation in this study. All patients were screened for eligibility for recruitment according to the Instructions For Use of the XIENCE V EES, and the TAXUS Liberté PES.
Randomization and patient enrollment
After verifying the selection (inclusion/exclusion) criteria, candidates were randomized according to an automatic centralized allocation system to 1 of 2 study arms. Selected sites recruited patients with MV-CAD into either the randomized section or the single-arm registry section (see the Online Appendix). No site enrolled patients simultaneously in the randomized study and the single-arm registry. The 2 study groups ran in parallel from October 2008 to March 2010.
Revascularization technique and treatment strategy
The most complete degree of revascularization was pursued, considering as equivalent both “anatomic,” which includes all vessels with a significant stenosis >70% irrespective of viable myocardium, or “functional,” that is, only vessels with significant stenosis >70% supplying viable ischemic myocardium (19). Because the completeness of the revascularization refers to the vessels suitable for PCI, small, tortuous, or diffusely atheromatous vessels were not treated, but all patients included in the study must have had at least 2 suitable major vessels treated with PCI and stent implantation. All major epicardial coronary arteries could be treated, with the exception of the left main trunk, and with a planned maximum of 4 DES implanted. Staged procedures to complete revascularization were allowed within 1 month of the index PCI.
The clinical risk of all patients entering the trial was classified according to the EuroSCORE (20), and the angiographic complexity of the treated lesions was assessed by the SYNTAX score obtained at baseline angiograms (21).
Stent implantation technique
Treatment of the target lesion could be performed with either a single stent or planned overlapping stents. Stents could be deployed either directly or after pre-dilation. Post-dilation with noncompliant balloons could be performed if appropriate. Bailout procedures were performed in cases of major dissection; occlusive complication; chest pain or ischemic electrocardiographic changes that do not respond to repeat balloon inflations and medical therapy. In the randomized study, the stent added in bailout was of the same type of that designated by the treatment allocation. In the single-arm registry, only EES could be added.
Before PCI, all patients were pre-treated with a loading dose of either ticlopidine 500 mg day for at least 48 h before, or clopidogrel 300 mg, ideally at least 6 h before PCI, and conventional doses of aspirin (325 to 500 mg in patients with acute coronary syndromes and 100 to 160 mg in stable patients). During the procedure, patients received intravenous heparin to maintain an activated clotting time over 300 s. After successful stent implantation, all patients received standard medications, including aspirin 100 to 160 mg/day, ticlopidine 250 mg twice daily, or clopidogrel 75 mg/day for at least 6 months. A regimen of dual antiplatelet treatment was maintained for 12 months if well tolerated in patients without augmented risk for bleeding. Statins were recommended in all patients.
Patients participating in the randomized trial had planned follow-up imaging and QCA at 9 months. Angiograms were analyzed by an independent angiographic core laboratory (Euro Imaging S.r.l., Rome, Italy) blinded to the stent type.
EXECUTIVE randomized trial primary endpoint
The primary endpoint of the randomized trial was in-stent lumen loss at 270-day follow-up. To avoid interlesion clustering of restenosis, the protocol specified that a single lesion would be randomly selected by computer for analysis of late loss. All randomized lesions were instead included in the analysis for other angiographic data.
EXECUTIVE randomized trial secondary endpoints
The secondary endpoints are as follows:
• Stent thrombosis at 30 days and 1 year adjudicated as per protocol and the Academic Research Consortium definitions (22).
• Angiographic in-segment minimal lumen diameter (MLD) and in-segment late loss at 270 days post-procedure.
• Revascularizations: target lesion, target vessel (TVR), or any revascularization at 30 days, and 1 year.
• Composite endpoint of cardiac death, myocardial infarction, Q-wave and non–Q-wave, and ischemia-driven target lesion revascularization at 30 days and 1 year.
• Composite endpoint of all-cause death, myocardial infarction (Q-wave and non–Q-wave), and TVR at 30 days and 1 year.
EXECUTIVE single-arm registry primary endpoint
The primary endpoint is a composite endpoint of all-cause death, myocardial infarction (Q-wave and non–Q-wave), and ischemia-driven TVR at 1 year.
EXECUTIVE registry secondary endpoints
The secondary endpoints of the registry are the same as the randomized study, except for the angiographic assessment at 270 days.
Data management and statistical methods
Independent study monitors verified all case report form data onsite. All major adverse cardiac events (MACE) were adjudicated by an independent clinical events committee blinded to treatment assignment with review of original source documentation (see the Online Appendix).
Sample size calculation of the EXECUTIVE randomized trial
The EXECUTIVE randomized trial aimed primarily to demonstrate noninferiority of the XIENCE V with respect to the TAXUS Libertè stent. If noninferiority was shown and the in-stent late loss was found to be lower in the XIENCE V arm, then superiority could be tested 2-sided at the 5% level. The sample size for the randomized part of the study was based on the primary endpoint of in-stent late loss at 270 days and on the following assumptions: 1-tailed noninferiority test; alpha = 0.05; randomization ratio 1:1; noninferiority margin delta 0.12; true mean in-stent late loss and standard deviation are assumed to be equal to 0.20 ± 0.41 mm in the XIENCE V EES arm: 0.16 ± 0.41 mm, 95% confidence interval (CI): 0.11 to 0.20; and true mean in-stent late loss and standard deviation are assumed to be equal to 0.30 ± 0.53 mm in the TAXUS Liberté stent arm. These assumptions are based on SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) trial results at 8 months (14).
Given the aforementioned assumptions, analyzing 81 lesions per arm provides more than 90% power. In order to account for dropouts and to ensure enough angiographic data, 200 patients were enrolled (approximately 100 EES and 100 PES). Sample size calculations were performed using NCSS-PASS 2002 (NCSS, Version 15 Statistical Software, Kaysville, Utah).
Sample size calculation of the executive registry
A sample size of 500 patients (400 included in the registry and 100 treated with the EES in the randomized study) produces a 2-sided 95% CI around clinical endpoint estimates. Assuming from previous studies a true 1-year incidence of the composite endpoint of all-cause death, myocardial infarction (Q-wave and non–Q-wave), and ischemia-driven TVR at 12 months rate comprised between 10% and 14%, the expected CIs, assuming 10% lost to follow-up, were estimated to comprise between 7.4% and 17.6% (16). Half the width of the CI would vary between 2.9 and 3.4; 95% CIs have been calculated using Clopper-Pearson.
The intention-to-treat population for the EXECUTIVE randomized trial consisted of all patients randomized to the study, regardless of the treatment actually received.
The primary outcome had to be tested using an analysis of covariance on 1 single randomized lesion by patient: the model included the treatment effect and post-procedure MLD value as quantitative covariate. Additionally, a supportive analysis was carried out by means of a repeated measures analysis model, using recorded data for all lesions and taking into account the interdependency of lesions within patients, by using a mixed model method with patient as random effect. Subgroup analysis was carried out on primary outcome using separate mixed models, including treatment, the subgroup factor and its interaction with treatment, baseline (post-procedure MLD) as covariate, and patient as random effect. A significant treatment by factor interaction indicates a significantly different treatment effect in 1 of the 2 categories. Patients and lesions baseline and characteristics were checked for homogeneity between XIENCE V and TAXUS Libertè groups using the Student t test for continuous variables, the Fisher exact test for binomial categorical variables, and the chi-square test for multinomial qualitative ones. The same methods were used to check homogeneity of characteristics between patients included in the randomized trial and in the registry.
Between October 2008 and March 2010, 600 patients were enrolled in 30 Italian sites. In the randomized study, 103 patients received 313 XIENCE V stents on 263 lesions, and 97 patients received 314 TAXUS Liberté stents on 235 lesions. In the single-arm registry, 400 patients were treated with 1,127 stents on 983 lesions (Fig. 1).
Baseline and procedural characteristics
Baseline characteristics of the patients were well matched between the 2 randomized groups, and were not substantially different from those of patients entered in the registry except for a higher number of patients with elevated troponin in the registry (Table 2). An additive EuroSCORE ≥6 was calculated in 32% of the randomized patients (34% in the EES arm, and 29.9% in the PES arm). The mean number of lesions treated was 2.5 ± 1.3 in each of the 3 groups. In the PES arm of the randomized study, the baseline lesion length was slightly longer (13.38 ± 6.56 vs. 12.17 ± 5.72, p = 0.03), there were some more bifurcation lesions (14.9% vs. 9.1%, p = 0.05), and distal dissections after stenting were reported more frequently in this group, which may explain the need for more stents per lesion (1.34 ± 0.64 vs. 1.21 ± 0.49, p = 0.01) (23) (Table 3).
The angiographic characteristics at baseline of the 2 randomized groups and a comparison between the patients enrolled in the registry and the randomized study are shown in Table 3. The baseline angiographic complexity as assessed by the SYNTAX score was low (12.7 ± 5.24), whereas the clinical risk was intermediate (mean logistic EuroSCORE = 4.79 ± 5.6), and these were almost identical among groups. A complete revascularization according to the PCI strategy planned at enrollment was obtained in all randomized cases and in 396 (99%) of the 400 patients entered in the registry. There were no differences regarding balloon pressure for stent deployment and direct stent implantation.
All patients entered in the study had 1-month follow-up. In the randomized study, the pre-specified angiographic follow-up at 9 months was obtained in 167 (84%) patients: 90 (87%) in the XIENCE V arm and 77 (79%) in the TAXUS Libertè arm. Clinical follow-up at 1 year was obtained in 99 and 91 patients in the XIENCE V and TAXUS Libertè groups, respectively. Follow-up of the registry study at 1 year was obtained in 392 patients (98%) (Fig. 1).
Table 4 shows the quantitative angiographic measurements of all lesions of the randomized arms and the results of the QCA at follow up observed in all patients with an angiographic follow up (419 lesions). Figure 2 shows in detail the late loss at 9 months of the randomized study as a single lesion per patient analysis: primary endpoint 90 XIENCE V and 77 TAXUS Libertè (Fig. 2A) and 225 XIENCE V and 194 TAXUS Libertè all lesions analysis (Fig. 2B). The primary endpoint of in-stent late loss in the analysis per single lesion was significantly less in the EES group compared with the PES group (−0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed in the analysis of all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001).
At 30 days, the incidence of clinical events was similar in the 2 randomized groups (1.0% and 2.2% in the EES and PES groups, respectively), and slightly higher in the registry (4.7%) (Table 5). At 1 year, 74% and 67% of patients were still under dual antiplatelet therapy in the EES and PES randomized groups, respectively, 20% and 28% were on aspirin alone, and 6% and 5% had stopped both drugs (p = 0.3). In the registry, 70% were still on dual antiplatelet therapy, 26% on aspirin, and 4% had stopped both drugs. In the XIENCE V group, 1 patient died 3 days after the procedure because of heart failure, and 1 patient died in the TAXUS Libertè group at 1 year likely because of a possible stent thrombosis. For the analysis of the clinical performance in the registry study, the 400 patients included in the registry were pooled with the 103 enrolled in the XIENCE V arm of the randomized study, for a total of 503 patients, 491 of whom had 1-year follow-up. The occurrence of clinical events was similar between patients entered in the registry and those included in the randomized study. Of note, most of the events classified as myocardial infarctions occurred within 1 month and were periprocedural, whereas very few cases occurred spontaneously during follow-up. The clinical outcome of the whole study population is detailed in Table 5.
Subgroup analysis for the randomized study
The results for the primary endpoint in subgroups of patients according to diabetic status, lesion length, multiple stenting, SYNTAX score, EuroSCORE, and the degree of vessel disease are shown in Figure 3. The analysis shows an overall significant superiority of the EES (p = 0.0026) and a consistent trend in favor of the EES in all subgroups. Significantly better angiographic outcomes with EES were observed in patients treated with a single stent per lesion (p = 0.001), patients with shorter lesions (p = 0.001), nondiabetic patients (p = 0.039), patients with 2-vessel disease (p = 0.019), and in patients with a higher EuroSCORE (p = 0.003).
Although implantation of DES in patients with MVD has become common practice, data about efficacy and safety of DES in this specific setting are scarce. Indeed, most of the available data derive from the analysis of subgroups of patients treated with multiple stenting in trials that allowed the inclusion of patients with maximum 2-vessel disease or with nonspecified MV-CAD (24,25), whereas in most of the seminal DES studies, this characteristic was a pre-specified exclusion criterion (26–30). Therefore, the study of the efficacy and safety of new-generation DES in this context deserves further study.
Our trial shows the angiographic superiority of EES over PES in the specific setting of patients with 2- and 3-vessel disease. Indeed, the late luminal loss observed in this study is very low, even lower than that reported in previous studies that assessed the same stents with a lower number of observations. This is true in all the treated lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001), as well as in the pre-specified analysis of 1 lesion per patient (−0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001).
From a clinical standpoint, the results observed at 1 year in the 503 patients treated with EES in the EXECUTIVE trial yielded a very low rate of MACE, with a composite of death, myocardial infarction, and ischemia-driven TVR of 9.2%, a reassuring finding considering that most myocardial infarctions were peri-procedural and not spontaneous during follow-up. Such results closely replicate the observations derived from lower-risk populations of MV patients such as those analyzed in the SPIRIT III and IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) studies (6.2%), as well as in the most recent Resolute All-Comers study that showed a 9.7% of all MACE at 1 year in the EES-treated arm (31,32).
The EES XIENCE V is a second-generation DES in which the drug is released from a thin (7.8 μm) nonadhesive, durable, biocompatible fluorinated copolymer onto a low-profile (0.0813-mm) strut thickness, flexible cobalt–chromium stent. Everolimus is an effective antiproliferative agent through the inhibition of growth factor–stimulated cell proliferation by causing cell cycle arrest in the late G1 stage in the cell cycle. Pre-clinical studies have shown more rapid and more complete endothelialization with this stent compared with sirolimus-eluting and paclitaxel-eluting stents (33), and clinical studies with the EES have demonstrated its superiority over the PES TAXUS Express (14–16).
The SPIRIT III randomized study enrolled 1,002 patients with mainly single coronary disease. Angiographic follow-up was planned for a subset of 564 patients at 240 days and showed that the EES was superior to the PES (in-segment late loss 0.14 ± 0.4 mm vs. 0.28 ±0.48 mm, p < 0.004). Moreover, at 2-year follow-up, treatment with EES compared with PES resulted in a significant 32% reduction in target vessel failure (10.7% vs. 15.4%; hazard ratio, 0.68; 95% CI: 0.48 to 0.98; p = 0.04) and a 45% reduction in MACE (7.3% vs. 12.8%; hazard ratio, 0.55; 95% CI: 0.36 to 0.83; p = 0.004) (14).
EXECUTIVE represents a unique population with MV-CAD patients treated with DES at an intermediate clinical risk (additive EuroSCORE ≥6 in 32% of the randomized patients), and with low angiographic complexity (SYNTAX score ≤22 in 95% of patients, mean 12.7 ± 5.24). The calculation of risk, taking into account both the angiographic severity of CAD and the clinical risk, has been proposed as a “global risk score,” a new classification that may better define the subgroups of patients with MV-CAD requiring myocardial revascularization (34). Patients enrolled in the EXECUTIVE trial represent a less complex cohort under an angiographic standpoint compared with the population assessed in the SYNTAX (28.4 ± 11.5) and the ARTS II (Arterial Revascularization Therapies Study II) studies (20.8 ± 9.5), with a logistic EuroSCORE 4.79 ± 5.6, compared with 3.8 ± 2.6 in the SYNTAX trial, and 2.12 ± 15.2 in the ARTS II trial (7,8).
The trial was not powered to test clinical differences. Furthermore, due to some protocol restrictions, few patients in the EXECUTIVE trial had intermediate SYNTAX scores; none was in the highest range >32, and none had left ventricular ejection fraction <30%. These exclusion criteria were introduced to allow patients with severe and diffuse forms of CAD the possibility of surgical revascularization, a treatment that was shown to offer better clinical results and that had proved more appropriate in patients with high angiographic complexity, as recommended in the most recent international documents (10–12). For the same reason, the criteria used in the SYNTAX trial to evaluate the completeness of revascularization could not be applied. Due to the limited sample size, some minor angiographic and procedural baseline characteristics were observed. For the same reason, the statistical analysis of subgroups yields nonsignificant results among subgroups with the lower number of observations.
The results obtained in EXECUTIVE trial show that patients with 2- and 3-vessel disease having low-to-intermediate SYNTAX scores, with intermediate clinical risk, and belonging to a low-to-intermediate “global risk score” classification, have significantly better angiographic results of multiple PCI with the use of EES rather than with PES. These data, supported by the low incidence of clinical events, may help to further improve the currently known outcomes of PCI in patients with MVD. The ongoing EXCEL study (Evaluation of XIENCE PRIME or XIENCE V versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) will investigate the performance of EES XIENCE V compared with coronary surgery in patients with left main stenosis eventually associated with MV-CAD, and will provide additional knowledge about myocardial revascularization strategies in patients with MV-CAD.
For an expanded list of the study investigators and the site locations, please see the online version of this paper.
This study was sponsored by Abbott Vascular Knoll-Ravizza S.p.A., Italy. Dr. Ribichini has received a fee from Abbott Vascular Knoll-Ravizza S.p.A. to design the study, develop the statistical analysis, and write the manuscript. Dr. Bartorelli is on the advisory board of Abbott Vascular. Drs. Lopera Quijada, Cappi, and Ribaldi are employees of Abbott Vascular Knoll-Ravizza S.p.A. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- coronary artery disease
- confidence interval
- drug-eluting stent(s)
- everolimus-eluting stent(s)
- major adverse cardiac event(s)
- minimal lumen diameter
- percutaneous coronary intervention
- paclitaxel-eluting stent(s)
- quantitative coronary angiography
- target vessel revascularization
- Received August 2, 2012.
- Revision received May 15, 2013.
- Accepted May 24, 2013.
- American College of Cardiology Foundation
- Rodriguez A.,
- Bernardi V.,
- Navia J.,
- et al.
- Daemen J.,
- Boersma E.,
- Flather M.,
- et al.
- Wijns W.,
- Kolh P.,
- Danchin N.,
- et al.,
- Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI)
- Levine G.N.,
- Bates E.R.,
- Blankenship G.C.,
- et al.
- Patel M.R.,
- Dehmer G.J.,
- Hirshfeld J.W.,
- Smith P.K.,
- Spertus J.A.
- Farooq V.,
- van Klaveren D.,
- Steyerberg E.W.,
- et al.
- Ribichini F.,
- Ansalone G.,
- Bartorelli A.,
- et al.,
- EXECUTIVE Trial Investigators
- Nashef S.A.M.,
- Roques F.,
- Gauducheau E.,
- Lemeshow S.,
- Salamon R.,
- the EuroSCORE study group
- Sianos G.,
- Morel M.-A.,
- Kappetein A.P.,
- et al.
- Cutlip D.E.,
- Windeker S.,
- Merhan R.,
- et al.,
- Academic Research Consortium
- Ellis S.G.,
- Vandormael M.G.,
- Cowley M.J.,
- et al.
- Kereiakes D.J.,
- Sudhir K.,
- Hermiller J.B.,
- et al.
- Caixeta A.,
- Lansky A.J.,
- Serruys P.W.,
- et al.,
- SPIRIT II and III Investigators
- Silber S.,
- Windecker S.,
- Vranckx P.,
- Serruys P.W.,
- RESOLUTE All Comers investigators
- Serruys P.W.,
- Farooq V.,
- Vranckx P.,
- et al.