Author + information
- Received August 26, 2011
- Revision received October 13, 2011
- Accepted November 14, 2011
- Published online March 1, 2012.
- Inge Wijnbergen, MD⁎,
- Harold Helmes, MANP⁎,
- Jan Tijssen, PhD†,
- Guus Brueren, MD, PhD⁎,
- Kathinka Peels, MD⁎,
- Jan Melle van Dantzig, MD, PhD⁎,
- Marcel van' t Veer, MSc, PhD⁎,‡,
- Jacques J. Koolen, MD, PhD⁎,
- Nico H.J. Pijls, MD, PhD⁎,⁎ ( and )
- Rolf Michels, MD, PhD⁎
- ↵⁎Reprint requests and correspondence:
Prof. Nico H. J. Pijls, Department of Cardiology, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ Eindhoven, the Netherlands
Objectives The goal of this study was to demonstrate superiority of sirolimus-eluting stents (SES) over bare-metal stents (BMS) and of abciximab over no abciximab in primary percutaneous coronary intervention (PCI).
Background Drug-eluting stents (DES) are increasingly used in primary PCI, but the recommendations for use in primary PCI are based on a few randomized controlled trials with selected patients. The usefulness of abciximab in primary PCI is not established.
Methods Nine hundred seven patients referred to the Catharina Hospital were randomized to SES or BMS, and to abciximab or no abciximab in a prospective, randomized, open 2 × 2 factorial trial with blinded evaluation. Primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of death, myocardial infarction (MI), stroke, repeat revascularization, and bleeding at 1 year (stent arm) and the composite of death, target vessel MI, target vessel revascularization (TVR), and bleeding at 30 days (abciximab arm).
Results At 1 year, the rate of MACCE was lower in the SES arm (16.5% vs. 25.8%, p = 0.001), mainly driven by less repeat revascularization (9.8% vs. 16.8%; p = 0.003) and without influencing the cumulative incidence of death and MI (5.2% vs. 5.8%; p = 0.68). At 30 days, the rate of the composite of death, target vessel MI, TVR, and bleeding was lower in the abciximab arm (8.2% vs. 12.4%, p = 0.04), mainly driven by less TVR due to less stent thrombosis (1.2% vs.7.4%, p < 0.001). However, bleeding complications occurred more frequently in the abciximab group (5.7% vs. 2.8%, p = 0.03).
Conclusions Primary PCI with SES reduces adverse events at 1 year, mainly by reduction of repeat revascularization, whereas abciximab reduces early stent thrombosis, at the expense of more bleeding complications. (Comparison of Drug Eluting and Bare Metal Stents With or Without Abciximab in ST Elevation Myocardial Infarction [DEBATER]; NCT00986050)
- bare-metal stent(s) (BMS)
- sirolimus-eluting stent(s) (SES)
- ST-segment elevation myocardial infarction (STEMI)
In patients with ST-segment elevation myocardial infarction (STEMI), primary percutaneous coronary intervention (PCI) with stenting is the treatment of choice (Class of Recommendation 1, Level of Evidence: A) according to the European guidelines (1) and the American College of Cardiology/American Heart Association guidelines (2). The recommendation for routine stenting in the guidelines is based on studies that have demonstrated the usefulness of bare-metal stents (BMS) in patients with STEMI (1). Although drug-eluting stents (DES) have been used widely in unstable angina and in acute myocardial infarction (MI), their routine use in STEMI is still a point of debate (1,3).
Randomized clinical trials and meta-analyses have shown that DES in STEMI and in stable patients reduce the rates of target vessel revascularization (TVR), with a similar long-term incidence of death or MI (4–7). However, concerns remain about the long-term safety with increased rates of late events, such as stent thrombosis due to pathological responses of the vessel wall to DES, especially in acute MI (8).
DES that elute sirolimus (SES) or paclitaxel from polymer carriers have demonstrated a reduction in TVR as compared with BMS in stable angina or non-STEMI patients (4,6,9). Some studies have shown that patients receiving SES have a significantly lower risk of restenosis, TVR, and major adverse cardiac events compared with patients receiving paclitaxel-eluting stents (9,10). To date, only a few medium-sized randomized trials have compared SES and BMS in STEMI (11,12), and for other DES, most studies were performed in selected patients.
Glycoprotein IIb/IIIa inhibitors are the most potent antiplatelet drugs. Glycoprotein IIb/IIIa inhibitors have been studied extensively in patients with non-STEMI before or after PCI (1,13). However, in studies on the routine use of abciximab in STEMI, no uniform results were obtained (3). The question remains whether routine administration of abciximab still has additional benefits, particularly when clopidogrel is used.
We designed the DEBATER (Comparison of Drug Eluting and Bare Metal Stents With or Without Abciximab in ST Elevation Myocardial Infarction) trial to investigate the superiority of SES over BMS in unselected patients with STEMI undergoing primary PCI and the superiority of abciximab over no abciximab in the clopidogrel era.
The DEBATER trial was an investigator-initiated, prospective, randomized, open 2 × 2 factorial trial with independent data management, statistical analysis, and blinded endpoint evaluation in patients from 10 regional referring centers who underwent primary PCI at 1 single PCI center. The study was initiated and coordinated by the Catharina Hospital Eindhoven and the Department of Biostatistics, Academic Medical Center–University of Amsterdam. The steering committee was responsible for the design, conduct, and reporting of the study. Data management and analyses were performed in collaboration with the Academic Medical Center–University of Amsterdam (the Netherlands). The study was approved by the institutional review board. All the authors reviewed and edited the manuscript, and vouch for the accuracy and completeness of the data and the analyses.
Patients 18 years of age or older with STEMI were eligible if they presented within 12 h of onset of symptoms. Patients who were on oral anticoagulation and patients who had received thrombolytic therapy or treatment with a glycoprotein IIb/IIIa inhibitor in the previous 24 h were not eligible. Other exclusion criteria were contraindications for DES, contraindications for clopidogrel or glycoprotein IIb/IIIa inhibitors, comorbid conditions with a predictable fatal outcome in the short run, cardiogenic shock, and inability to give informed consent.
Eligibility was assessed and informed consent was obtained by the interventional cardiologist immediately after the patient had arrived at the catheterization laboratory and before coronary angiography was performed.
After informed consent had been obtained, randomization was done using a 24-h computer-generated random-allocation system that randomly allocated patients on a 1:1:1:1 basis to treatment with a DES or a BMS and to treatment with abciximab or no abciximab with a factorial design. The DES was always a SES (CYPHER, Cordis Corporation, Bridgewater, New Jersey), whereas the choice of the BMS was left to the discretion of the operator. All patients received aspirin (300 mg chewed or 500 mg intravenously), clopidogrel (600 mg) and a fixed bolus of intravenous unfractionated heparin (5,000 IU) in the ambulance. Before angiography, all patients received an additional intravenous bolus of heparin (5,000 IU). After primary PCI, aspirin 80 mg per day was given indefinitely, and clopidogrel was prescribed (75 mg/day) for at least 1 month after BMS and 6 to 12 months after SES. Patients allocated to abciximab received a 0.25 mg/kg bolus after stent placement followed by an infusion of 0.125 μg/kg/min for 12 h. Directly after the procedure, patients were transported back to the referring hospital with the exception of those who were hemodynamically unstable, who stayed in the Catharina Hospital. These logistics of rapidly admitting patients to the Catharina hospital and criteria for transporting back to the referring hospital, are well defined in a covenant between all hospitals and ambulance services involved and is an exemplar for primary PCI in the Netherlands (14).
Patients were followed for 1 year for adverse events by reviewing hospital and chart records at the referring hospitals, by telephone calls, and in some cases, by a written questionnaire. If necessary, we contacted the patient's general practitioner. All events were adjudicated by a clinical endpoints committee under blinded conditions.
Definitions and endpoints
The primary endpoint for the stent comparison was defined as the composite of death, any MI, stroke, repeat revascularization, and bleeding (MACCE) within 1 year. Reinfarction was diagnosed on the basis of a new episode of chest pain followed by creatine kinase or troponin concentrations exceeding twice the upper limit of normal or new Q waves on the electrocardiogram. Recurrent MI during the first 48 h was diagnosed when there was a decrease from a previous peak value of enzyme level followed by a subsequent rise to a level exceeding twice the upper limit of normal. All reinfarctions were considered related to the target vessel territory unless electrocardiography or angiography unequivocally documented otherwise. Stroke (ischemic or hemorrhagic) was defined as an acute neurological event of at least 24 h of duration, with focal signs and symptoms and without evidence supporting any alternative explanation, confirmed by computed tomography or magnetic resonance imaging, or by pathological confirmation. Bleeding was defined in accordance with the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial criteria as the occurrence of any of the following: intracranial bleeding, retroperitoneal bleeding, intraocular bleeding, access site hemorrhage requiring surgery or a radiological or interventional procedure, reduction in hemoglobin concentration of ≥4 g/dl, reoperation for bleeding, or use of any blood product transfusion (15). Secondary endpoints were death and MI and the individual components of the primary endpoint within 1 year. Stent thrombosis was a secondary endpoint.
For the abciximab comparison, the primary endpoint was the composite of death, MI (target vessel related), TVR, and bleeding within 30 days.
TVR was defined as any ischemia-driven repeat PCI of the target vessel or bypass surgery of the target vessel. The target vessel was defined as the entire major coronary vessel of the culprit lesion. For the 30-day window, we also evaluated the occurrence of bleeding and stent thrombosis. Stent thrombosis was defined as the definite or probable occurrence of a thrombotic event, according to the Academic Research Consortium classification (16).
Statistics and data analysis
Analysis was performed on an intention-to-treat basis. We calculated that, with 2 × 427 patients in the stent comparison, the study had 85% power to detect a significant decrease in the primary endpoint from 17% to 10%. For the abciximab comparison, the study had 80% power to show a significant decrease in the primary endpoint from 4% to 1% with 2 × 424 patients. Statistical analysis was done with SPSS (version 17.0, IBM, Armonk, New York).
Time-to-first-event distributions were plotted as Kaplan-Meier curves, and the log-rank test was used for comparison. Event rates at 30 days and 1 year were estimated from the Kaplan-Meier curves. We present Kaplan-Meier curves for the overall groups defined by the stent randomization and by the abciximab randomization, after statistical tests (logistic regression analysis) had confirmed the assumptions of no interaction between the stent intervention and the abciximab intervention. Relative risks (RR) were calculated by dividing the Kaplan-Meier estimated rate of an event in the SES or abciximab group by that in the BMS or no abciximab group, respectively. The 95% confidence interval (CI) for the relative risk was calculated using the standard errors from the Kaplan-Meier curve. The significance of differences in event rates between treatment groups was assessed using the log-rank test.
Categorical variables were expressed as frequency (percentage) and were compared using the chi-square or Fisher exact test as appropriate. Continuous variables were expressed as means and standard deviations and were compared using an unpaired t test or the Mann-Whitney U test. A 2-tailed value of p < 0.05 was considered to indicate statistical significance. Because the 30-day endpoints related to the abciximab randomization were different in timing and mechanism from the 12-month endpoints related to the stent randomization, we did not apply statistical corrections for multiple comparisons based on the stent and abciximab randomizations.
Baseline characteristics and angiographic findings
The trial profile is displayed in Figure 1. From January 2006 to May 2008, 2,977 patients from 10 regional centers were referred to the Catharina hospital for primary PCI for STEMI. Out of a total of 2,977 patients presenting with an acute STEMI, 907 were included in the study and randomly assigned to 1 of the 4 previously described groups. Reasons why patients were not eligible or did not give informed consent are mentioned in Figure 1. As a control that no bias had occurred with respect to patients who were eligible, but in whom no informed consent was obtained or who did not enter the study for other reasons, baseline characteristics were compared with the baseline characteristics of the randomized patients. No differences in any of the baseline characteristics (demographic data, risk factors, electrocardiographic and angiographic data at presentation, and time intervals) were present between these groups. In 35 of the randomized patients, no PCI was performed for reasons mentioned in Figure 1. None of these patients received abciximab. In case a SES could not be implanted, implantation of a BMS was allowed.
Baseline characteristics of all groups were well matched (Table 1). Medication during hospitalization was well matched, but in 55 patients assigned to no abciximab, the operator decided to treat with abciximab for clinical reasons in accordance with the guidelines. The median age of patients was 60 years, and 76% of the patients were men. There were slightly more inferior wall MIs than anterior wall infarctions. Initial Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 in the infarct-related artery was seen in about 16% of all 4 groups. The distribution of final TIMI flow was comparable between all groups, with 92% to 95% of patients having a TIMI flow grade 3. In 55 patients assigned to no abciximab, the operator decided to treat with abciximab for clinical reasons, mainly because of the occurrence of distal embolization. Mean time interval from onset of symptoms to reperfusion was 165 min and was similar in all groups (Table 1).
Clinical outcomes: comparison of SES with BMS
Table 2 shows the clinical outcomes at 1 year for patients randomized to SES or BMS. Kaplan-Meier curves are presented in Figure 2. The primary endpoint (a composite of death, MI, stroke, repeat revascularization, and bleeding within 1 year) occurred in 70 patients (16.5%) in the SES group and in 115 patients (25.8%) in the BMS group (RR: 0.64; 95% CI: 0.49 to 0.84; p = 0.001) (Fig. 2). This difference was driven by less repeat revascularizations (9.8% vs. 16.8% for SES vs. BMS; p = 0.003) (Fig. 2). All-cause mortality within 1 year was 2.6% (11 deaths, 8 of which had cardiovascular causes) in the SES group and 2.2% (10 deaths, 7 of which had cardiovascular causes) in the BMS group (p = 0.74). The composite of death and nonfatal MI occurred in 22 patients (5.2%) in the SES group and in 26 patients (5.8%) in the BMS group at 1 year (p = 0.68) (Fig. 2). The individual rates of stroke and significant bleeding were also similar in the 2 groups through the 12 months of follow-up. Stent thrombosis occurred in 4% of the patients in both groups (Table 2).
Clinical outcomes: comparison of abciximab with no abciximab
Table 3 shows the clinical outcomes at 30 days and at 1 year for patients randomized to abciximab or no abciximab. Kaplan-Meier curves are presented in Figure 3. In the abciximab group, the primary endpoint (a composite of death, target vessel MI, TVR, and bleeding at 30 days) occurred in 36 patients (8.2%) randomized to abciximab and in 54 patients (12.4%) randomized to no abciximab (RR: 0.65; 95% CI: 0.43 to 0.99) (p = 0.04) (Fig. 3). The difference in the primary endpoint was driven by TVR because of stent thrombosis, which occurred in 4 patients (1.0%) in the abciximab group versus 29 patients (6.7%) in the no abciximab group (p < 0.001) (Fig. 3). At 30 days, bleeding occurred in 25 patients (5.7%) in the abciximab group versus 12 patients (2.8%) in the no abciximab group (p = 0.03) (Fig. 3).
All-cause mortality within 1 year was 2.1% (9 deaths, 7 of which had cardiovascular causes) in the abciximab group and 2.8% (12 deaths, 9 of which had cardiovascular causes) in the no abciximab group (p = 0.49) (Table 3). There were also no differences in the occurrence of stroke between the 2 groups.
The lower incidence of TVR at 1 year in the abciximab group as compared with the no abciximab group (6.6% vs. 11.1%, p = 0.02) was nullified by a higher incidence of bleeding in the abciximab group as compared with the no abciximab group (6.6% vs. 3.3%, p = 0.02). Most bleedings involved the femoral access site, but 1 patient had a hemorrhagic stroke and died.
This study shows in the first place that in primary PCI in patients with STEMI, use of SES is superior to BMS, mainly because of a significant reduction of repeat revascularization procedures within 1 year; and in the second place that routine administration of abciximab cannot be advocated in these patients because the reduction in the stent thrombosis rate is counterbalanced by an increase in major bleeding without a noticeable effect on overall outcome.
SES versus BMS
Our findings confirm the results of several other studies in more selected patients, indicating superiority of DES versus BMS in primary PCI. As in most of these studies, we found that the rate of death or nonfatal MI at 1 year was not different between SES and BMS, but a significant reduction in repeated revascularizations at 1 year was found. This is in line with a meta-analysis by Brar et al. (17) in 33,873 STEMI patients, showing a reduction in restenosis rate without an increase in the incidence of death or MI when DES was used compared with BMS.
Of note, we also found significantly more nontarget vessel revascularizations in the BMS group, which should probably be explained by more complete revascularizations (due to eye-balling) in patients undergoing ischemia-driven reinterventions (Table 2).
Our results extend the results of several other randomized clinical trials in more selected patients to a general population with STEMI (11,12,18–22). Two previous studies with SES in STEMI are of comparable size with ours. The TYPHOON (Trial to assess the use of the CYPHer sirolimus-eluting coronary stent in acute myocardial infarction treated with BallOON angioplasty) study was the first randomized clinical trial that compared SES and BMS in 712 STEMI patients and demonstrated a significant reduction in the occurrence of TVR in patients who received SES compared with BMS (11). The trial protocol in that study required visualization of the culprit lesion before randomization. Randomization was only performed immediately after coronary angiography if the infarct-related artery was patent or after re-establishing blood flow by the placement of a guide wire or by balloon angioplasty. In contrast, we included patients before angiography, avoiding any selection bias. Our inclusion criteria are more comparable to those of the MULTISTRATEGY (MULTIcentre evaluation of Single high-dose Bolus TiRofiban versus Abciximab with Sirolimus-eluting STEnt or Bare-Metal Stent in Acute Myocardial Infarction StudY) trial. In this trial, 744 STEMI patients were randomized to SES with a high-dose bolus of tirofiban and to BMS with abciximab. At 8 months, the rate of MACE (composite of any death, reinfarction, and clinically driven TVR) was higher among those who were treated with BMS (14.5%) compared with those who were treated with SES (7.8%; p = 0.004) (12). In comparison with both trials, our rate of TVR in the BMS group is somewhat lower. This could explain why we found less reduction in the occurrence of TVR at 1 year. Furthermore, the very strict selection criteria in the TYPHOON trial and the shorter duration of follow-up in the MULTISTRATEGY study may play a role, as may the fact that our study was a single-center study that included consecutive patients with STEMI referred for primary PCI and therefore better reflects daily practice.
Our rate of stent thrombosis at 1 year was 4% in both stent groups, which is in line with the results of other trials (11,21,23,24). This finding also corresponds with the results of a more recent analysis on stent thrombosis in the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, where no relation was found between the type of stent implanted (DES vs. BMS) and the occurrence of stent thrombosis up to 2 years (24).
Abciximab versus no abciximab
We found a significant reduction in the rate of the primary endpoint (the composite of death, target vessel MI, TVR, and bleeding at 30 days) in patients treated with abciximab, mainly driven by a significant reduction in the need for reintervention because of stent thrombosis. Treatment with abciximab significantly reduced the rate of stent thrombosis, without increasing the risk of stroke. However, treatment with abciximab significantly increased the rate of bleeding complications. Of notice, the incidence of target vessel–related MI was much lower than the incidence of stent thrombosis, which needs some explanation: patients with acute in-hospital recurrent or aggravating chest pain were immediately sent back to the catheterization laboratory. This explains both the high rate of definite, angiographically shown stent thrombosis and the low rate of early target vessel–related MI.
A meta-analysis of the trials that have assessed the value of periprocedural administration of abciximab in addition to aspirin and heparin in acute STEMI showed that abciximab reduced 30-day mortality significantly without increasing hemorrhagic stroke and major bleedings (25,26). However, it remained to be elucidated whether this benefit is maintained in patients who receive 600 mg of clopidogrel before primary PCI. We demonstrated in our study that abciximab started during primary PCI also provides an additional benefit with respect to stent thrombosis in patients pretreated by 600 mg of clopidogrel. We have not studied the pre-hospital or pre-catheterization use of abciximab as studied in the FINESSE (Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events), MISSION (Abciximab administration before primary PCI for STEMI), and BRAVE-3 (Value of Abciximab in Patients With Acute MI Undergoing PCI After High Dose Clopidogrel Pretreatment) trials. Finally our positive results should be set alongside the recent suggestion of bivalirudin monotherapy as an alternative to unfractionated heparin plus abciximab in the HORIZONS-AMI trial (27). Bivalirudin had a better net clinical benefit because of less severe bleeding rates, although early thrombotic complications were somewhat higher. In contrast, our study does show a decrease in early thrombotic complications.
Study strengths and limitations
This study has several specific strengths that should be mentioned. In the first place, it is a single-center study in a high-volume center performing approximately 1,500 primary PCIs per year. Second, the rate of included patients is very high (36% of all eligible patients), and the inclusion criteria were very broad, thereby reflecting everyday practice and minimizing any possible selection bias. Third, patients were randomized before angiography was performed. Fourth, all baseline characteristics of eligible patients who were not participating because of lack of informed consent or other reasons, were not different from the randomized patients. A limitation of the present study is the lack of blinding of operators during primary PCI. For SES versus BMS, such blinding is impossible. For abciximab versus no abciximab, it could have been done. Our results may not apply to low-volume centers and regions lacking a well-organized referral system. Another limitation is the follow-up of 1 year, and therefore, very late stent thrombosis, which may occur after SES implantation, is not accounted for. Finally, newer and faster-acting thienopyridines could also modify the results of this study.
Our study shows the superiority of the drug-eluting sirolimus stent versus the BMS in routine unselected patients admitted for primary PCI for acute STEMI and corroborates observations in earlier studies to the benefit of DES in primary PCI. The benefit is mainly attributable to reduction of repeat revascularization in the first year. Furthermore, this study does not support routine use of abciximab in addition to aspirin, clopidogrel, and heparin: although acute stent thrombosis in the first 30 days was reduced, this was accompanied by more bleeding complications, and overall outcome at 1 year was not influenced.
The authors thank all the referring hospitals for their contribution in collecting follow-up data: Maxima Medical Centre Eindhoven, Maxima Medical Centre Veldhoven, Tweesteden Hospital Tilburg, St Elisabeth Hospital Tilburg, VieCurie Hospital Venlo, Laurentius Hospital Roermond, Jeroen Bosch Hospital Den Bosch, St Maartens Gasthuis Weert, Bernhoven Hospital Oss, St Anna Hospital Geldrop, Elkerliek Hospital Helmond. Furthermore, they wish to thank all personnel from the catheterization laboratory in the Catharina Hospital Eindhoven.
The DEBATER study was supported by unrestricted research grants from Johnson & Johnson (Cordis), Guidant, Abbott, and the Friends of the Heart Foundation (“Stichting Vrienden van het Hart”) in Eindhoven, the Netherlands. The sponsors were not involved in the study design, monitoring, data analysis, or presentation. Dr. Pijls received institutional research grants from St. Jude Medical, Abbott, and Maquett, and is consultant to St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- bare-metal stent(s)
- confidence interval
- drug-eluting stent(s)
- myocardial infarction
- percutaneous coronary intervention
- relative risk
- sirolimus-eluting stent(s)
- ST-segment elevation myocardial infarction
- Thrombolysis In Myocardial Infarction
- target vessel revascularization
- Received August 26, 2011.
- Revision received October 13, 2011.
- Accepted November 14, 2011.
- American College of Cardiology Foundation
- Silber S.,
- Albertsson P.,
- Aviles F.F.,
- et al.,
- Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology
- Kushner F.G.,
- Hand M.,
- Smith S.C. Jr..,
- 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)
- Kirtane A.J.,
- Gupta A.,
- Iyengar S.,
- et al.
- Nakazawa G.,
- Finn A.V.,
- Joner M.,
- et al.
- Bertrand M.E.,
- Simoons M.L.,
- Fox K.A.,
- et al.
- Brueren B.R.G.
- Cutlip D.E.,
- Windecker S.,
- Mehran R.,
- et al.
- Brar S.S.,
- Leon M.B.,
- Stone G.W.,
- et al.
- Menichelli M.,
- Parma A.,
- Pucci E.,
- et al.
- Di Lorenzo E.,
- Sauro R.,
- Varricchio A.,
- et al.
- Kelbaek H.,
- Thuesen L.,
- Helqvist S.,
- et al.
- Dangas G.D.,
- Caixeta A.,
- Mehran R.,
- et al.
- Van de Werf F.,
- Bax J.,
- Betriu A.,
- et al.,
- Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology