Primary PCI and the Indistinct 120 Min Time Limit

Peter Sinnaeve; Frans Van deWerf

Disclosures

Eur Heart J. 2020;41(7):867-869. 

There is no doubt that timely performance of PCI in ST-elevation myocardial infarction (STEMI) patients by an experienced team is superior to fibrinolysis, as clearly confirmed by the famous meta-analysis of Keeley et al., published in 2003.[1] Since this publication, the number of both catherization labs and primary PCI procedures have increased exponentially across the world. A key question however is: what is 'timely performance of PCI'? In this regard, the current ESC guidelines state that primary PCI is the preferred procedure if it can be performed by an experienced team within 120 min from STEMI diagnosis by ECG.[2] Where does this time cut-off of 120 min come from? No specifically designed study has ever addressed this issue. Nevertheless, there is general agreement among experts that for patients presenting first to a non-PCI facility this transport-related delay limit is indeed ~120 min. The guidelines usually refer to the study by Pinto et al. from the National Registry of Myocardial Infarction of the USA which has shown that in two matched populations of almost 10 000 STEMI patients each (from 1994 to 2006), primary PCI loses its survival advantage at 30 days over in-hospital fibrinolysis if the PCI-related delay (in this registry door to balloon minus door to needle) is >120 min, with a 95% confidence interval (CI) of ~100–170 min.[3] The data from this and other registries are rather old, and most patients who were treated with fibrinolysis did not undergo routine transfer to a PCI hospital for rescue PCI or early routine angiography within 24 h, which improves outcomes in patients receiving fibrinolysis.

In the real world, it is very difficult for the emergency team to estimate on the spot the beginning of the primary PCI (i.e. according to the ESC guidelines: crossing the lesion with the wire). Several time delays indeed need to be considered, as illustrated in Take home figure: time to organize the transport to the PCI hospital, the transport time to the door of the PCI hospital, the transfer to the catheterization lab within the PCI hospital, preparing the patient for the PCI procedure, sheath insertion, identifying the infarct vessel, and crossing the culprit lesion with the wire. Obviously, it is assumed here that the team that is going to do the PCI procedure is available in the hospital and that a cath lab room is immediately available. Taken together, the process from pre-hospital diagnosis to wire crossing can be fairly complex, and it is difficult to fathom that a pre-hospital medical team is always able to make a fair assessment of all these possible delays. In addition, because additional unexpected delays may occur, e.g due to weather conditions and traffic jams, on top of the known structural delays mentioned above, it is not a surprise that in a substantial number of STEMI patients primary PCI is performed beyond the recommended time delay of 120 min. Does this have an impact on outcome and, if so, can something be done to mitigate the negative effect?

Take home figure.

Time delays in primary PCI. ECG, electrocardiogram; ER, emergency department; FMC, first medical contact.

In this issue of the European Heart Journal, the FAST-MI (French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction) investigators from France have compared the 5-year outcomes in STEMI patients who underwent primary PCI beyond the recommended 120 min from ECG diagnosis (n = 830, 28%) with those patients who had timely primary PCI (n = 1288, 54%) and with patients who received a fibrinolytic before transfer to a PCI hospital as part of a pharmaco-invasive strategy (n = 824, 28%).[4] A pharmaco-invasive strategy implies administration of a fibrinolytic followed by immediate transport to a PCI hospital with rescue PCI in patients with failed fibrinolysis or planned early (but not immediate) coronary angiography within 24 h in those with lytic success. In the propensity score-matched cohorts of the FAST-MI study, 5-year survival was 89.3% in the pharmaco-invasive group and 81.8% in late primary PCI patients [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.28–2.44, P < 0.001] and 89.3% in patients who received timely primary PCI (HR 1.01, 95% CI 0.70–1.44, P = 0.97). Also, for the combined endpoint of death, re-infarction, or stroke at 5 years, a significantly worse outcome was found in the late primary PCI group when compared with pharmaco-invasive-treated patients: 85.2% vs. 76.5% (HR 1.64, 95% CI 1.23–2.18, P = 0.001). The 5-year mortality benefit of a pharmaco-invasive strategy over late primary PCI was observed irrespective of age, location of infarct, and gender. Only in patients who received the fibrinolytic late after onset of infarction was a benefit over late primary PCI no longer present.

What can be concluded from this registry? First, in spite of an excellent ambulance service in France (called SAMU), more than a quarter of STEMI patients did not receive timely primary PCI. This percentage did not decrease over the years (27% in 2005, 29% in 2010, and 30.5% in 2015), suggesting inherent problems with getting patients from a non-PCI facility to the catheterization lab in many places in France. Secondly, giving a fibrinolytic to patients presenting early to a non-PCI facility before transfer to a PCI hospital is associated with a survival and overall clinical benefit at 5 years when compared with primary PCI performed beyond 120 min after diagnosis. Several other randomized studies and registries have also shown a benefit of this strategy.[5–9] A consistent finding in randomized studies of a pharmaco-invasive treatment vs. primary PCI is a lower risk of cardiogenic shock, most probably due to earlier reperfusion of the ischaemic myocardium.[10]

Invasive cardiologists have been and some still are reluctant to perform PCI in patients who received a fibrinolytic before the procedure because of the possible prothrombotic effect of the lytic[11] and the associated risk of thrombotic complications of the procedure and because of bleeding at the arterial access site. With the co-administration of P2Y12 antagonists and the use of radial access, these risks have become minimal. Still, there remains the risk of intracranial bleeding, especially in the elderly. After halving the dose of the bolus of tenecteplase in the STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction) trial, no intracranial bleeding was observed in the cohort of 97 patients above the age of 75 years without loss of efficacy for clot lysis.[5] This reduced dose of tenecteplase is now being studied in a much larger population of STEMI patients ≥60 years of age in the STREAM-2 study (ClinicalTrials.gov identifier: NCT02777580).

It is a huge responsibility for the emergency team (usually without a cardiologist) not only to make the diagnosis of STEMI but also to select the best reperfusion strategy. If it is unlikely that a PCI can be performed within 120 min, a fibrinolytic should be given before transporting the patient to the PCI hospital, as recommended by the guidelines and strongly supported by this new study. As shown in this and previous registries, this unfortunately does not always happen for several reasons: most importantly, underestimation of the consecutive time delays,[12] but also lack of knowledge of fibrinolytic treatments, no availability of a fibrinolytic in the ambulance, instructions from invasive cardiologists not to give fibrinolytic therapy, and the fear of an intracranial haemorrhage especially in elderly patients. (Re)-education of emergency physicians as well as cardiologists about the benefits of a pharmaco-invasive treatment, the development of a safer fibrinolytic regimen (minimalizing the risk of an intracranial bleeding), implementation of a default use of radial access, and close monitoring of actual performance within STE MI networks may help to increase the use of a pharmaco-invasive treatment in patients who cannot receive a primary PCI within 120 min from diagnosis. Especially in patients presenting early to a non-PCI facility, the benefit of this reperfusion treatment may be substantial since fresh coronary clots are easier to lyse.

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