OUP user menu

Emerging data and decision for optimizing STEMI management: the European perspective

Giulio Guagliumi
DOI: http://dx.doi.org/10.1093/eurheartj/sup008 C19-C24 First published online: 22 May 2009


Univocal management of STEMI patients in Europe is necessary to extensively implement guidelines and allow uniform standard of care and outcome. The European Society of Cardiology released recently new guidelines for the treatment of STEMI patients. These recommendations emphasize the importance of early reperfusion therapy. To achieve this goal, local networks have to be improved, to promote early in-ambulance treatment, including thrombolysis or to transfer immediately the patient to a primary PCI hospital, avoiding delay in vessel reopening. Several studies indicate that the most impactful strategy on short and long term outcomes is to privilege primary percutaneous coronary intervention vs thrombolysis, when an efficient and competent unit is available, but only if reduced door-to-balloon times are possible. Unfortunately, throughout Europe there are wide differences in primary PCI centers in terms of geographic distribution, organization and level of competence. The priority should be to obtain a more homogeneous standard of care, based on a consensus triage, efficient regional network and outcome data auditing. The TAPAS study results indicate that thrombus aspiration prior to PCI is associated with improved tissue reperfusion and lower rate of cardiac mortality at 1 year follow-up. Also, the anti-thrombotic strategy during STEMI needs to be balanced between the effectiveness on thrombus removal and the emergent risk of bleeding. The HORIZONS-AMI trial demonstrates that bleeding has a significant impact on early and long term mortality, with better outcomes with new anti-thrombin agents (bivalirudin) compared to the combination of heparin + GP IIb/IIIa inhibitor, however at the cost of some significant increase of stent thrombosis immediately following the acute intervention (first 24 hours). Trans-radial interventions during STEMI, a rapidly growing approach all over the Europe, need to be considered as a promising component of the global strategy that attempts to reduce the incidence of acute bleeding. Further, preventive therapy using evidence based medicine prescription, in-hospital as well at the time of discharge, is a gold standard to be pursued for a more favorable long-term outcome. Although a global and uniformed European strategy in STEMI is far to be obtained, and difficult to be applied in various regional frameworks, common goals based on new recommendation of the European Society of Cardiology should be pursued to try to optimize the system of care.

  • Acute myocardial infarction
  • Percutaneous coronary intervention
  • Thrombus
  • Guidelines
  • Door-to-balloon time


Establishment of a consistent, unified, and optimal approach to the management of patients with ST-segment elevation myocardial infarction (STEMI) in Europe is a necessary component to improving patient outcomes. However, there are various questions that remain open including whether a ‘core strategy’ is ultimately achievable based on the impact of national and regional geographical considerations, as well as medical resource and infrastructure. The core strategy for the management of STEMI patients will be based upon the capabilities of regional STEMI network impacting achievable door-to-balloon (DTB) times and the choice between primary percutaneous coronary intervention (PCI) vs. thrombolysis as well as multiple management decisions including the role of pre-hospital care, thrombus aspiration, and radial vs. femoral access (Figure 1).

The ST-segment elevation myocardial infarction ‘chain of survival’

The STEMI Chain of Survival is an educational construct that can be used to target global improvements in patient care.1 The STEMI chain begins with an emphasis on the role of the patient in the recognition of early heart attack symptoms and immediate request for help, and works its way through the critical elements of pre-hospital treatment via the emergency response system (EMS), emergency department (ED) evaluation and treatment, and reperfusion care (Figure 2).

Figure 2

The STEMI Chain of Survival (Reprinted from Ornato JP.,1 with permission from the American Heart Association).

The new European Society of Cardiology (ESC) guidelines for the management of patients with STEMI emphasize the importance of early reperfusion therapy,2 and as a result, the chain is evolving to include reperfusion therapy at the centre stage. According to the ESC guidelines, recommended logistics for pre-hospital triage/care include an ambulance with a 12-lead ECG recorder/defibrillator, and time delays of <10 min for ECG transmission, <5 min for tele-consultation, and <120 min to first balloon inflation.2

The optimal pharmacological management of STEMI has been the subject of significant investigation over the last decade, and numerous studies have demonstrated that compared with fibrinolytic therapy, primary balloon angioplasty in STEMI enhances survival and reduces rates of reinfarction, stroke, and intracranial bleeding.3 New ameliorations to balloon angioplasty, including the routine implantation of bare metal coronary stents and glycoprotein (GP) IIb/IIIa inhibitors, have further improved the early safety profile of primary PCI.310 GP IIb/IIIa inhibitors, as an adjunct to primary PCI for STEMI, are used in a substantial proportion of cases on the basis of studies demonstrating that abciximab, as an adjunct to primary balloon angioplasty and stenting, reduces sub-acute thrombosis, recurrent myocardial infarction (MI) or ischaemia, early repeat intervention, and may be associated with enhanced survival.4,711

However, several challenges with primary PCI remain to be overcome, including optimizing STEMI network capabilities with a focus on use of experienced high volume centres and shorter DTB times, ameliorating the management and outcomes of high-risk patients such as the elderly, and improving the safety of contemporary strategies while avoiding the negative impact of haemorrhagic complications.3

Door-to-balloon times

A common goal in the management of STEMI is to shorten the time from symptom onset to effective myocardial reperfusion. There are two main concepts regarding how this can be accomplished. The first method is to bring the treatment to the patient, whereby an ambulance with thrombolysis capability can provide pre-hospital diagnosis, triage, and care. The second method involves bringing the patient directly to the treatment, whereby networks are established, to a PCI-capable hospital (Figure 3).2 An analysis from the HORIZONS-AMI trial demonstrated that presentation to a non-PCI centre was the strongest predictor of DTB time>90 min (Odds ratio 9.1 compared with presentation to a PCI centre, P < 0 .0001).12

Figure 3

Pre-hospital management (Reprinted from Van de Werf F et al.,2 with permission from the European Society of Cardiology).

When a patient is not brought directly to a PCI centre, ED physician activation of the catheterization laboratory and immediate transfer of the patient to a promptly available catheterization laboratory significantly reduces the final door-to-balloon time, leading to a reduction in myocardial infarct size, length of hospital stay, and total hospital costs.13 The relationship between DTB time for primary PCI and late cardiac mortality is dependent on the individual patient’s risk profile. A study of >2300 patients found that prolonged DTB times (≥2 vs. <2 h) were associated with higher late mortality in high-risk patients (defined as those >70 years of age with anterior MI, and Killip class III or IV) (32.5 vs. 21.5%, P = 0.0002).14

Regional systems of care

Another important logistical component in the treatment of STEMI patients is bringing the patient to an appropriate facility with an experienced staff. Recent data suggest that the outcomes in STEMI patients treated with primary PCI are dependent on the experience of the centre. For example, an analysis of >22 000 patients with STEMI in the NRMI-4 registry revealed reduced rates of in-hospital mortality and DTB time >90 min in patients receiving reperfusion therapy as a function of hospital primary PCI ‘specialization’ (Table 1).15 The term ‘specialization’ referred to the relative proportion treated patients with primary PCI, over the total of reperfusion-treated patients (primary PCI plus fibrinolytic therapy); a concept distinct from the overall number of STEMI patients treated or primary PCIs performed at a hospital (i.e. hospital volume). In another series of 1575 STEMI patients with high (>32) TIMI risk index score treated with primary PCI in 30 centres, rates of 30 day mortality were lowest in centres with more experience, with the most significant difference observed between centres performing more or less than 60 primary PCI procedures per year (Figure 4).16

Figure 4

Importance of experience to the outcomes of high-risk ST-segment-elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

View this table:
Table 1

Rates of in-hospital death and delayed reperfusion in the NRMI-4 registry.

In-hospital deathDoor-to-balloon >90 min
% of STEMI patients treated with primary PCIRR (95% CI)P-valueRR (95% CI)P-value
Lowest quartile (≤34%)ReferenceReference
Second quartile (>34–62.5%)0.78 (0.58–1.05)0.1060.93 (0.85–1.01)0.089
Third quartile (62.5%–88.5%)0.74 (0.54–1.01)0.0610.88 (0.78–0.97)0.005
Highest quartile (>88.5%)0.64 (0.46–0.88)0.0060.78 (0.67–0.88)<0.001
P-value for trend=0.008P-value for trend <0.001
  • PCI, percutaneous coronary intervention.

Given the evidence that timely performance of primary PCI is optimal in the majority of patients with STEMI, the future design for the provision of cardiac services will play a critical role in providing prompt access to this therapy. However, it is anticipated that multiple barriers and problems will be encountered if the current environment is disrupted by the establishment of an excessive number of competitive centres of care.

In the USA, a market research study was conducted at the request of the AHA, to assess the desirability, feasibility, and potential effectiveness of establishing regional systems of centres of care for STEMI patients to improve quick access to PCI.17 The results of this study indicate that different stakeholders do indeed recognize the multiple barriers to improved primary PCI and agree that centralized systems are necessary. But, improvements to existing systems will have an impact on payers, physicians, and hospitals, particularly non-PCI hospitals.17

Throughout Europe, as well as within individual nations, there are vast differences among centres with respect to the capability of the centre as well as the prevalence of PCI for STEMI as a percentage of each centre’s PCI activity. As a result, one of the top priorities should be to make STEMI care more homogenous, and a number of efforts have been developed to achieve this goal. In Vienna, a system was developed that created uniformity among experienced catheterization laboratories by the implementation of a central triage network via the Viennese Ambulance System. Patients are brought to one of several participating hospitals based upon the day of the week, allowing for permanent availability of catheterization labs and teams during non-official catheter times, and ensuring that only experienced interventionalists are on duty.

According to the American College of Cardiology Foundation (ACCF); American Heart Association (AHA); American College of Physicians Task Force on Clinical Competence and Training, a high-quality PCI program requires appropriately trained, experienced, and skilled physician operators.18 However, the operator does not work in a vacuum. An operator needs a well-maintained high-quality cardiac catheterization facility to practice effectively. Also, the operator depends on a multidisciplinary institutional infrastructure for support and response to emergencies. Thus, to provide quality PCI services, the institution must ensure that its catheterization facility is properly equipped and managed, and that all of its necessary support services, including data collection, are of high quality and are readily available.18

The development of national, regional, and state registries for outcome assessment will promote a shift of the paradigm surrounding quality of PCI from a mere collection of procedure volume to objective assessment of clinical outcomes.18 The ESC guidelines also recommend that survey and registries are performed to verify the real-life daily practice.2

Emerging data

Thrombus aspiration

In STEMI patients, the ‘no-reflow’ phenomenon is defined as inadequate myocardial reperfusion after successful re-opening of the infarct-related artery. No-reflow may be caused by various factors, including downstream vascular embolization of thrombotic or atheromatous debris, that can cause prolonged myocardial ischaemia and is associated with a significant increase in the risk of clinical complications. Adjunctive devices aiming at the prevention of distal embolization have recently been evaluated. Results of the TAPAS study indicate that aspiration of thrombus prior to PCI is associated not only with improved tissue reperfusion, but also lower rates of cardiac mortality at 1 year compared with conventional PCI.19,20 However, the question remains as to whether thrombus aspiration should be used in all patients, or only in those where a significant high thrombus burden exists.

Antithrombin therapies

The HORIZONS-AMI trial evaluated 3602 patients with STEMI undergoing primary PCI who were randomized to antithrombin therapy with bivalirudin alone or heparin plus GP IIb/IIIa inhibition. Stent eligible patients were further randomized in a 3:1 ratio to receive the paclitaxel-eluting Taxus stent or a bare metal stent.21 Compared with heparin plus a GP IIb/IIIa inhibitor, therapy with bivalirudin alone resulted in significantly lower rates of overall mortality (2.1 vs. 3.1%, P = 0.048) and cardiac-related mortality at 30 days (1.8 vs. 2.9%, P = 0.03) and at 1 year (2.1% vs. 3.8%, P = 0.005). Bivalirudin-treated patients also had significantly reduced rates of major bleeding (4.9 vs. 8.3%, P < 0.001).21,22

Despite the clear mortality advantage observed with bivalirudin, there was a higher rate of acute (≤24 h) stent thrombosis in this group compared with heparin plus GP IIb/IIIa inhibitors (1.5 vs. 0.3%, P = 0.0002).22 An adjusted Cox model with stent thrombosis and major bleeding as time-updated covariates indicated that although the hazard of definite stent thrombosis at 30 days was higher than major bleeding (hazard ratio 10.62 vs. 6.22), the number of attributable deaths to major bleeding was more than three times higher in patients who experienced major bleeding (4.5 vs. 15.1).23 These results suggest that major bleeding has a significant impact on mortality, and may help to explain why mortality was lower with bivalirudin despite an increase in acute stent thrombosis.

Secondary prevention

The newly updated ESC guidelines advocate secondary prevention, as patients with STEMI are at high risk for new events, with higher post-discharge mortality than in the general population. The guidelines recommend treatment with antiplatelet therapy (aspirin and thienopyridines), beta-blockers, ACE-inhibitors, and statins in all patients.2

In the HORIZONS-AMI trial, 96% of patients received guideline-based treatment at discharge and the compliance between the randomization arms for thienopyridines up to 1 year was high and equivalent between both arms (post-discharge = bivalirudin 98.7%, heparin, 92.7%; 1 year = bivalirudin, 96.1%, heparin, 95.7%).22 Similar compliance was also observed between the stent randomization groups, with 100% of patients using aspirin post-discharge and at 1 year, and also high rates of thienopyridine use (post-discharge = Taxus and Express, 100%; 1 year = Taxus, 89.9%; Express, 85.7%). The success of secondary prevention depends on the physician’s capability to express the importance to the patient.


The diverse national and regional frameworks currently in place across much of Europe mean that the strategies required to manage and optimize outcomes in patients with STEMI need to be implemented on a national and regional level. However, while a pan-European perspective and consensus may be difficult to obtain, it remains desirable as we share a common goal in optimizing patient management and outcomes through the implementation of effective STEMI networks.

Conflict of interest: none declared.


View Abstract