New plots in the partnerships of contemporary STEMI care: Revival of the ‘ménage à trois’?

Over the past decades many initiatives have contributed to today’s ST segment elevation myocardial infarction (STEMI) care. In short, there are three important partners in the field. First, in the late 1980s–early 1990s the landmark ISIS-2 trial demonstrated that mortality could be reduced with the simple use of daily aspirin.1 In addition to antiplatelet therapy, fibrinolytic therapy was introduced, which was a major step forward in the treatment of STEMI.2 With this in combination with aspirin, the mortality reduction achieved was more pronounced than the summed effect of each of the respective agents.1 Second, the flipside of pharmacological reperfusion was early and late reocclusion, for which adjunctive anticoagulation and subsequent revascularization were introduced.3–5 The third breakthrough in STEMI care was the introduction of primary angioplasty,6 which has been proven the best reperfusion therapy if performed timely and in an experienced centre.5 Especially in patients presenting later than 3–4 h after symptom onset, the absolute benefits of primary percutaneous coronary intervention (PCI) over pharmacological reperfusion are undisputed.7 Mechanical reperfusion therapy has the advantage of very high success rates of restored coronary patency (>90–95%), but it takes some time to initiate the procedure. Fibrinolytic therapy can be initiated early, for example in the ambulance, works especially well on ‘fresh clots’, but achieves coronary patency in about two-thirds of patients within 60–90 min. After thorough analysis of the available evidence, it was concluded that primary PCI is to be the preferred strategy if it can be initiated within 90 min of first medical contact.5 For STEMI patients presenting very early (i.e. <3 h from symptom onset) the more recent comparative trial results seem less conclusive7,8 and this is the population that the Strategic Reperfusion Early After Myocardial infarction (STREAM) study has focused on.9 In fact, in many regions patients will primarily be treated in non-PCI centres or the primary PCI will not be deliverable within the guidelines-specified time interval. In this context, STREAM provides important information on an alternative reperfusion strategy of fibrinolysis followed by mandatory, triaged angiography in all patients. Although it should be acknowledged that the study was not conventionally designed and powered to detect an a priori defined difference in the primary endpoint, post-hoc calculations suggest that outcome of this dedicated fibrinolytic strategy did not clearly differ from primary PCI. Importantly, the angiography strategy consisted of 1) early angiography for rescue PCI in patients without clinical or electrocardiographic signs of reperfusion and 2) standard, routine angiography 6–24 h after fibrinolysis in all other patients. Notably, this is different from a strategy of standard routine early angiography after fibrinolytic therapy: this so called facilitated PCI strategy demonstrated the potential for harm or no benefit.10,11 In the present substudy of STREAM the authors present data in relation to the location of randomization, with 352 patients randomized in community hospitals, and 1508 in the pre-hospital setting. Baseline characteristics of the former were significantly worse, and time to reperfusion was significantly longer than for patients randomized pre-hospital. These clear clinical differences did not translate into worse outcomes, which may be related to the fact that comparisons between groups are subject to insufficient statistical power. The authors and readers should therefore exercise caution regarding overestimating the findings of this subgroup analysis. All efforts for acute STEMI care should be focused to facilitate pre-hospital triage and treatment of patients, especially in regions with (predominant) use of fibrinolysis. However, notwithstanding the limitations of the presented comparison, the reported data are unique of their kind, providing invaluable information on different contemporary reperfusion strategies. This especially holds true for information on patients with failed pharmacological reperfusion therapy. Patients randomized in community hospitals who went for rescue PCI had significantly higher rates of the primary endpoint (death, shock, congestive heart failure, reinfarction at 30 days) as compared with patients who underwent rescue PCI after pre-hospital fibrinolysis. This is not only a mere reflection of the higher baseline profile of the community hospital group. Interestingly, there was a significantly lower rate of rescue PCI in patients with fibrinolysis initiated at a community hospital. This may reflect a certain threshold to transfer patients to an intervention centre, which will in part be related to the associated time delays before rescue PCI could be initiated. Rescue was performed about 3 h after fibrinolysis in patients randomized in the community hospitals, about 45 min later than in patients from the pre-hospital group. Probably, treating physicians in the community hospital group may have preferentially transferred the patients for whom a rescue was considered most necessary. In STREAM, only those community hospitals with a well developed hub-and-spoke relationship with a PCI capable centre were considered for participation in the trial. Therefore, treatment delays in daily practice will be much longer than the data presented in the present report. In order to realize a time window within which rescue PCI is still expected to convert benefit in terms of myocardial salvage, a different approach from that employed in this study is warranted. Given the difficulty of predicting successful reperfusion, and the time delays involved with transfers after a 90-min clinical and electrocardiographic evaluation, it is imperative that all patients who receive fibrinolysis will be immediately transferred to a PCI capable hospital. During transport a 90-min electrocardiogram can be performed, if applicable. Thus, the key message of this report is not to follow a strategy of ‘lyse and see’, but to initiate transfer to a PCI centre immediately. Another striking finding of this observational report is that 87% of patients randomized in a community hospital were presented after activation of a pre-hospital system of care, without receiving pre-hospital reperfusion therapy and without direct triage for primary PCI. Of course, in a percentage of patients this will be related to the clinical presentation, where the ambulance staff will not have initiated therapy in the absence of a clear-cut presentation. However, in many cases this reflects a suboptimally organized pre-hospital care system. The second message of this report on contemporary STEMI care is that there is still room for improvement of pre-hospital networks to diagnose, triage and treat patients with myocardial infarction.12 A third important observation relates to the adjunctive antiplatelet and anticoagulation regimens. Consistently, primary PCI has been associated with lower intracranial bleeding rates than fibrinolysis.5 Whereas for primary PCI the choice of antithrombotic therapy is less patient dependent, fibrinolysis requires a much more patient tailored approach, which is more susceptible to suboptimal treatment, even in study settings.10 In addition, for primary PCI the more potent antiplatelet drugs can be used, which should be avoided in patients receiving fibrinolytic therapy.5 These are important aspects for the organization of ambulance care in regions with both primary PCI and fibrinolysis. In addition, special attention is warranted for the elderly, to ensure safety of this dedicated pharmaco-invasive strategy. Lowering the dose of low molecular weight heparin, lowering the dose of fibrinolysis and skipping the loading dose of clopidogrel are key elements. Importantly, even without the use of reperfusion therapy lives can be saved with the simple intervention of daily antiplatelet therapy1,5 and anticoagulation therapy.5,13 In conclusion, the STREAM investigators are to be commended for pulling off a trial on fibrinolytic therapy in an era with difficult funding and a global shift toward primary PCI. In the context that in many regions of the world primary PCI cannot be (timely) performed, this study provides valuable lessons for optimal STEMI care. After a period where fibrinolysis and mechanical reperfusion were more or less considered to be mutually exclusive, the present study has shed new light on an old partnership. With a well performed triage of subsequent angiography, there is room for a revival of the ‘ménage à trois’, incorporating all three key partners in acute STEMI care. The main premises are immediate transfer to a PCI capable hospital after initiation of fibrinolysis, and paying specific attention to the antithrombotic regimen for the elderly. Appreciating the more straightforward approach of primary PCI, and the outcomes of properly powered comparisons,7 we believe that in parallel to initiatives to organize STEMI networks for a dedicated pharmaco-invasive reperfusion strategy there should be extra focus and resources to realize optimal primary PCI networks where possible.