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Optimizing reperfusion therapy in acute ST-elevation myocardial infarction by a pharmaco-invasive treatment approach in a well-organized network

Kurt Huber
DOI: http://dx.doi.org/10.1093/eurheartj/ehr427 1184-1186 First published online: 25 November 2011

This editorial refers to ‘Safety and efficacy of a pharmaco-invasive reperfusion strategy in rural ST-elevation myocardial infarction patients with expected delays due to long-distance transfers’, by D.M. Larson et al., on page 1232

Importance of time and time delays in reperfusion therapy of acute ST-elevation myocardial infarction

Treatment of acute ST-elevation myocardial infarction (STEMI) has undergone important changes in the last few years.13 After implementation of primary percutaneous coronary intervention (pPCI; usually balloon dilatation followed by stent implantation) as the method of choice, previous pharmacological reperfusion strategies (fibrinolytic therapy) have rapidly lost their importance or have even been neglected in areas where it is believed that pPCI can be offered to all STEMI patients within the recommended time frame of 90 (to 120) min.

However, the real situation still is that a significant number of patients referred for pPCI, ranging from 20% to 80%, cannot be treated within this time frame. As time progresses, the benefits of mechanical reperfusion therapy decline,4 with negative influence on short- and long-term mortality.5,6In this respect there is more concern with younger patients (<65 years) with anterior wall infarctions of short duration due to the hypothesis that the ‘golden hours’ of treatment (within the first 3–4 h after symptom onset) are critical to safe myocardium,79 while during the later course of myocardial infarction, the curve representing time after symptom onset and the magnitude of benefit ‘flattens’, and time is less of a critical determinant.7 However, time delays are not always important for patients referred for pPCI, and short and longer time delays have been shown to lead to similar mortality rates in mechanically reperfused patients,912 while success of fibrinolytic therapy is always time dependent.9,11,13

Network organization

To avoid unacceptable time delays, STEMI guidelines as well as recent overviews have outlined the importance of organizing systems of care (networks) in order to shorten delay times from electrocardiogram (ECG) diagnosis (first medical contact) to first balloon dilatation in an experienced catheter laboratory by experienced personnel.3,9,13,14An unexpected time delay from first medical contact to first balloon dilatation is not due to a lack of existing networks with respective treatment resources per se, but rather the absence of clear, systematic protocols for identifying treatment-eligible patients, and ensuring that therapies are available in a timely manner 24 h a day, 7 days a week, 365 days a year.9,13

Impact of a pharmaco-invasive reperfusion strategy on clinical outcome

A pharmacological reperfusion strategy is offered pre-hospital and at present comprises fibrinolysis followed by early routine angiography and intervention especially in patients in whom pPCI cannot be offered in time (Figure 1).3,15,16 Such a pharmaco-invasive strategy provides a theoretical balance of risk and benefit, ensuring an open artery acutely, and, in the successfully reperfused patient, decreasing re-infarction through stabilizing residual stenoses as well as providing additional risk stratification through assessment of coronary anatomy.11,1724 Although not tested in a prospective randomized study, the early use of clopidogrel also seems to be of importance in improving outcome data in STEMI patients referred for pPCI,25,26 and might add to the success of pre-hospital pharmacological treatment.

Figure 1

Studies comparing early routine percutaneous coronary intervention (PCI) vs. standard therapy after fibrinolytic therapy (with permission from Halvorsen and Huber, Thrombosis and Haemostasis 2011).16

Larsen and co-workers27 have now presented registry data from the experience with the Minneapolis STEMI network utilizing half-dose fibrinolysis in addition to clopidogrel 600 mg and unfractionated heparin combined with transfer for immediate PCI in STEMI patients presenting to remote rural hospitals (≥60 miles away from the catheter centre). They report 2634 consecutive STEMI patients including 660 transferred from remote hospitals. Thirty-day mortality, stroke, major bleeding, or reinfarction/ischaemia were comparable in patients receiving a pharmacoinvasive strategy and those presenting directly to the PCI centre, despite a significantly longer door-to-balloon time. Accordingly, the authors concluded that within a regional STEMI system of care, a pharmaco-invasive strategy utilizing half-dose fibrinolysis, clopidogrel, and unfractionated heparin, combined with emergent transfer for immediate PCI, may be a safe and effective reperfusion strategy for STEMI patients with expected delays due to long distances to a PCI centre. These results strongly support earlier investigations, which demonstrated similar short- and long-term clinical outcome for pPCI and fibrinolysis immediately followed by angiography and PCI.9,11,28

The authors have to be congratulated for generating and demonstrating these important data, which confirm a new level IA recommendation in the recent European myocardial revascularization guidelines,3 namely to transfer patients, who initially received fibrinolytic therapy, immediately to a PCI-capable hospital in order to perform rescue PCI in non-responders to pharmacological reperfusion, or to perform diagnostic angiography in responders to therapy within 24 h and to offer elective PCI to those 80–85% of STEMI patients who need additional mechanical treatment after successful fibrinolysis.11,17 Other treatment modalities, e.g. to accept long-distance transfers to catheter centres without optimal pre-treatment, or to transfer patients after initiation of fibrinolytic therapy to a nearby cardiac care unit without catheter facilities, and thereby to risk interhospital transfer with prolonged time delays until mechanical reperfusion,21,29 are still clinical practice in some areas worldwide, but should be avoided based on these insights.

Still unanswered questions

Interestingly, a recently published subgroup analysis of the TRANSFER-AMI trial30 revealed a strong heterogeneity in the treatment effects of a pharmaco-invasive strategy after fibrinolysis for STEMI, which was unexpectedly associated with beneficial outcome only in patients with a low-to-intermediate GRACE risk score, while the early invasive strategy was associated with worse outcome in high-risk patients. This seems irrational and adds to other unanswered questions including the optimal timing of PCI after initial fibrinolysis, which has been shown to be harmful when performed within 2 h of initiation of fibrinolytic therapy.31 The ongoing prospective, randomized STREAM trial32 in patients with acute STEMI of short duration will provide further information on the optimal treatment in a STEMI patient cohort, which is, based on hypothetical consideration and registry data, believed to benefit in particular from a pharmaco-invasive strategy.

Conflict of interest: K.H. has received lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Pfizer, Sanovi-Aventis, and The Medicines Company.


  • The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.