Fibrinolysis may widen the time window for primary angioplasty.

Recently published clinical trials have demonstrated superiority of primary percutaneous coronary intervention (PPCI) over lysis in ST-elevation myocardial infarction (STEMI) treatment. Current practice guidelines have established PPCI as a preferred method of reperfusion in STEMI, as long as it can be performed within 90 min from patient’s first medical contact. However, in the majority of cases achieving this 90 min time goal proves impossible, mainly because the STEMI care is not streamlined enough between different levels and components of health care system. Accordingly, the optimization of treatment strategy in STEMI patients, who for one reason or another exceed the 90 min delay, is one of the hottest topics in cardiology today. The GRACIA-2 study is certainly an important contribution to that issue. Clinical trials with lytics have shown a significant correlation between the time of their administration after the symptoms onset and the mortality. First studies with primary PCI demonstrated no such correlation, which was attributed to higher efficacy of angioplasty to re-open the infarct related artery (IRA) than what lytic therapy could provide (irrespective of ischaemia duration). Only ‘door-to-balloon time’ and not ‘symptoms onset-to-balloon time’ have appeared to correlate with patient mortality. An additional factor contributing to that effect might have been a low patient risk profile. It was later confirmed by Antoniucci et al., who concluded that a relationship between pain onset to PCI and mortality is evident only in ‘non-low risk’ patients. Brodie et al. demonstrated a relationship of the delay of PPCI in STEMI and the presence or absence of left ventricular contractile function recovery in long-term follow-up. More recently, a convincing relationship between the ischaemia duration and mortality assessed at 1 year was found by De Luca et al., who correlated every additional 30 min delay with an increase in 1 year mortality by 7.5%. In patients with full reperfusion after lysis, there is no optimal time set for coronary intervention. A message from the prematurely terminated ASSENT-4 study seems to be that one should avoid combination of full dose lytic followed by immediate angioplasty because it might be associated with transient prothrombotic effect of lytics and lack of optimal antiplatelet (clopidogrel) treatment regimen. However, the main limitations of ASSENT-4 study were that it was an open-label study and it was stopped before the pre-specified number of patients was enrolled. The time from randomization to balloon inflation was rather short (,120 min in both groups, median time between bolus tenecteplase and PCI was only 104 min). Due to this reason, the time gain for reperfusion with this lytic treatment was probably short in many patients. Also due to the absence of an infusion after bolus administration of unfractioned heparin and no loading dose of clopidogrel might have led to lower than expected IRA patency in baseline angiography, and decreased potential benefit of early reperfusion in tenecteplase treated patients. On the other hand, the WEST study investigators concluded that combination of lytic (preferably prehospital) with interventional treatment is safer when a slightly prolonged time interval was observed between lytic administration and PCI than in ASSENT-4 trial. However, it is known that the excessive prolongation of this timeframe increases risk of refractory ischaemia. Recurrent myocardial infarction (reMI) has a significant impact on 30-day and 1 year survival. According to the European Society of Cardiology guidelines, every patient after successful lysis should be transferred for coronary angiography within 24 h. The GRACIA-2 authors report angioplasty performed at 3–12 h after initial lysis, with the mean time to PCI 6 h (median 24.6 h). It certainly is a significant difference in comparison to ASSENT-4 trial, where time to PCI was much shorter, and likely reflects the problems of daily practice more adequately. Furthermore, transfer of patients for primary PCI in DANAMI-2 and PRAGUE-2 trials was associated with the reduction in composite end-point in 30-day follow-up (death/reMI/stroke) in comparison to lysis without routine angiography/PCI. The composite end-point occurrence was 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. * Corresponding author. Tel: þ48 602217202; fax: þ48 612977500. E-mail address: [email protected] † doi:10.1093/eurheartj/ehl461