Transporting STEMI patients for primary PCI: a long and winding

EDITORIAL

European Heart Journal (2016) 37, 1041–1043 doi:10.1093/eurheartj/ehv640

Transporting STEMI patients for primary PCI: a long and winding road paved with good intentions? Peter R. Sinnaeve 1,2 and Frans Van de Werf2* 1

Department of Cardiovascular Medicine, University Hospitals Leuven, Leuven, Belgium; and 2Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium

Online publish-ahead-of-print 18 December 2015

This editorial refers to ‘Early ST elevation myocardial infarction in non-capable percutaneous coronary intervention centres: in situ fibrinolysis vs. percutaneous coronary intervention transfer’†, by X. Carrillo et al., on page 1034. Primary percutaneous coronary intervention (pPCI) is the preferred reperfusion therapy for patients presenting with an ST-segment elevation myocardial infarction (STEMI).1 However, as the majority of hospitals worldwide do not have catheterization facilities, the performance of a pPCI within the appropriate time frames by an experienced interventional team is often far from straightforward. Indeed, pPCI comes with several logistic challenges: one needs a well-oiled pre-hospital network with a commonly agreed protocol, trained medical or paramedical transport personnel, and 24/7 expedite services. In contrast to pPCI, fibrinolytic therapy is universally available, does not require additional technical expertise, and can be administered via a bolus to eligible patients by (para)medical personnel in the pre-hospital setting. Especially in patients presenting early (i.e. ,3 h) after symptom onset, pre-hospital fibrinolysis is an excellent alternative for patients who cannot undergo a pPCI within 1 h.2,3 Contemporary guidelines therefore explicitly list maximal tolerated transfer delays of 90 min, or even a maximal 60 min treatment delay in cases where the patient first presents directly to a PCI-capable hospital or when presenting within 2 h after symptom onset (Figure 1).1 On aggregate, guidelines recommend using fibrinolysis given in the ambulance or on-site when the expected time from first medical contact (FMC) to start of PCI exceeds 120 min. Achieving these goals consistently in the majority of patients is challenging: recent real-world registries clearly show that both reperfusion strategies are not optimally used at all. In a 22 481 patient US registry, for instance, only 43% of transferred STEMI patients with estimated drive times exceeding 30 min achieved a first-contact-to-balloon delay below 120 min, while only half of the patients with a drive time .60 min received fibrinolysis. 4

These inherent system delays when transferring patients are certainly not trivial, as they appear to have the highest negative impact on mortality, significantly more than treatment and patient-related delays.5 To improve these widespread deficiencies in STEMI care, initiatives to form customized local STEMI networks or to improve the co-ordination in and between existing STEMI networks are being promoted throughout the world, as recently reviewed by Huber and colleagues in this journal.6 In 2009, Catalonian cardiologists, working in a geographically confined autonomous region of Spain with 7.5 million inhabitants and 10 PCI-capable hospitals (half of which only offered pPCI services during weekday office hours), stepped up to the challenge and identified several key operational interventions to increase the number of STEMI patients undergoing timely pPCI within their established and well-regulated network. Under the new rules, only patients with a centrally monitored expected PCI delay .120 min were to receive fibrinolysis, preferably pre-hospitally. Within a few months, they observed a doubling of the monthly number of pPCIs, and a decrease of treatment delays by 20 –40%.7 In the present analysis from this registry, featured in this issue of the journal, Carrillo and colleagues compared the delays and 30-day mortality rates between fibrinolysis and pPCI in a subset of patients initially presenting at a ‘non-capable PCI centre’, within 2 h after symptom onset.8 The good news is that this collaborative effort resulted in reaching at least one of their major goals set in their intention paper from 2009, i.e. .90% of patients were treated with pPCI. The bad news is that the price to pay for this gain was disappointingly high, in terms of inappropriate treatment delays, although not unlike those reported in other registries.4,9 pPCI patients had a median delay between FMC and PCI of 119 min, resulting in only half of these patients being treated within the maximal 120-min limit set by the guidelines, and certainly fewer met the 90- or 60-min thresholds for transport to the PCI centre. The FMC-to-fibrinolysis delays were even more astonishingly and inexplicably long: the median delay was 45 min, and less than a third of the few lytic-treated

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 † doi:10.1093/eurheartj/ehv619.

* Corresponding author. Department of Cardiovascular Sciences, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium. Tel: +32 16 342111, Fax: +32 16 342100, Email: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].

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Editorial

Arrival PCI center

FMC Direct Transfer

PCI

DTB £ 60 min FMC-to-Balloon £ 90 minutes (£ 60 minutes if < 2h after symptom onset

Symptom onset

Diagnosis £ 10 min

Patient-related delay

System-related delay

ECG £ 10 min

FMC-to-Balloon £ 120 minutes DTB £ 60 min

DIDO £ 30 min

Indirect Transfer

Arrival nonPCI center

Departure non-PCI center

Arrival nonPCI center

Fibrinolysis

Arrival PCI center

PCI

FMC

immediate rescue PCI or angiography ≥3 -< 24h

DTN £ 30 min Fibrinolysis in ambulance

Arrival non-PCI center

Figure 1 European Society of Cardiology guideline-recommended maximal treatment delays for patients directly and indirectly transferred to a PCI-capable centre. FMC, first medical contact; PCI, percutaneous coronary intervention; DIDO, door-in-door-out; DTN, door-to-needle; DTB, door-to-balloon.

patients in this registry actually received tenecteplase within the guideline-recommended limit of 30 min. This suggests that very few patients actually received fibrinolysis in the pre-hospital setting (i.e. in the ambulance; this is not reported in this analysis), despite about half of the patients having been diagnosed in the ambulance, and despite this being a top goal on the network’s implementation priority list from 2009.7 Delaying fibrinolysis until admission to the hospital might have represented a missed opportunity, as 5-year mortality was significantly lower with pre-hospital fibrinolysis than after transport for primary PCI in the contemporary French registry FAST-MI.10 Both in FAST-MI and in the randomized STREAM study, pre-hospital fibrinolysis matches pPCI in early presenters (within 3 h from symptom onset).2,10 In the absence of a detailed triage protocol in this analysis or the intention paper, it is difficult to gauge how exactly patients were selected for or denied fibrinolysis by the co-ordinating centre, other than taking the expected transport-related delay into account. For instance, 7.5% of the lytic-treated cohort were initially in cardiogenic shock. Although not a formal contraindication for fibrinolysis, the preferred immediate reperfusion strategy for these patients is pPCI. The authors did not report how many of these subsequently received an invasive management and how many contributed to the 17 deaths in the overall fibrinolysis group. In addition, it is not clear where the fibrinolysis-treated STEMI patients were first identified by a medical team, i.e. in the pre-hospital setting, in a non-PCI centre, or in a non-24/7 PCI-capable hospital outside office hours or during the weekend. Non-24/7 PCI-capable hospitals, constituting half of the 10 PCI centres in this registry, have lower volumes and less expertise; this practice is strongly discouraged by the European

Society of Cardiology (ESC) guidelines (class IB recommendation for 24/7 services).1,11 It is also unclear whether patients presenting to the five non-24/7 centers during out-of-office hours or during the weekend were even included in this analysis, and what their patients’ treatment and treatment delays might have been. Were the long FMC-to-needle as well as FMC-to-PCI delays reported here because the co-ordinating centre took too much time estimating the traffic-related delays or telephoning around to find an available catheterization lab? In any case, the use of a central co-ordinating centre might have needlessly complicated and delayed STEMI care. Such an approach also appears to be in contrast to the ‘direct call’ advocated by the guidelines and, incidentally, also included by the authors in their 2009 implementation list. Post-fibrinolysis care, in addition, also appeared to be suboptimal, with only 60% of patients receiving an angiography within the recommended 24 h time frame. No details were given on the respective proportion of patients undergoing either rescue or planned intervention. In addition, the number of successfully reperfused patients who underwent a PCI before the recommended 3 – 24 h time frame in this network setting is unclear, this practice being discouraged by the guidelines after ASSENT-4 PCI.1,11,12 Frankly, the main conclusion proposed by the authors, i.e. that ‘in situ fibrinolysis had worse prognosis than patient transfer [for pPCI]’ appears not to be supported by the findings reported here. Overall mortality was not significantly different between the two treatment strategies, although the robustness of this finding is very low as more patients were lost to follow-up than were known to have died at day 30. Although there appeared to be a trend, both a propensity score-adjusted and -matched analysis also failed to


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show a statistically significant association between treatment allocation and 30-day outcome. The less stringent multivariable analysis using approximately the same limited number of variables (n ¼ 6) turned out to be just significant (P ¼ 0.04). Given the arbitrary selection of patients from the overall cohort, the low absolute number of events, and the low number of patients in the fibrinolysis group, combined with a sizeable proportion of patients lost to 30-day follow-up (5% in the pPCI arm and even 9% in the fibrinolysis arm), the results presented here are at best inconclusive. The same issues, in addition to selection bias, probably also explain the counterintuitive and unaddressed finding that longer patient-related delays tend to be associated with lower 30-day mortality risk in the authors’ multivariable analysis. The Catalonian experience and registry does seem to offer two other opportunities. First, the authors might want to try to identify the barriers to expediting reperfusion therapy in their all-inclusive registry, which would be of tremendous help to other European regions struggling to improve STEMI care. Secondly, since it appears that the authors have extensive data on STEMI care in Catalonia before the new implementation in 2009, 7 it would also be interesting to evaluate whether implementing the changes that have shifted STEMI care towards almost exclusively pPCI has decreased treatment and system delays over time and, most importantly, has improved overall outcome. Although the present analysis unfortunately does not help to identify the best reperfusion and transfer strategy for STEMI patients presenting early and not being able to undergo expedited pPCI, the authors’ commendable efforts not only to implement a network protocol but also to measure and report its performance do highlight a critical issue related to the transfer of STEMI patients: they demonstrate that despite the best intentions and clear guidelines, many real-world STEMI patients continue to be treated poorly, even in a well-organized system in an affluent European region with world-class medicine. Indeed, the road to expedited pPCI, paved with the best intentions, appears to be long, winding, and bumpy. It also underscores that one can only improve the care for STEMI patients if one also keeps track of the actual delays, as explicitly mandated by the guidelines. In the end, it is critical that regional STEMI networks throughout Europe take note of the Catalonian effort, and aim to treat all within the guideline-recommended maximal delays, as outlined in Figure 1. Conflict of interest: F. VdeW. reports grants and personal fees from Merck, grants and personal fees from Boehringer Ingelheim, personal fees from AstraZeneca. P.R.S reports institutional grants and fees from AstraZeneca and institutional fees from Boehringer Ingelheim.

References 1. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van’t Hof A, Widimsky P, Zahger D. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012;33:2569 –2619. 2. Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y, Sulimov V, Ortiz FR, Ostojic M, Welsh RC, Carvalho AC, Nanas J, Arntz H-R,, Halvorsen S, Huber K, Grajek S, Fresco C, Bluhmki E, Regelin A, Vandenberghe K, Bogaerts K, Van de Werf F. Fibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med 2013;368:1379 –1387. 3. Sinnaeve PR, Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Lambert Y, Danays T, Soulat L, Halvorsen S, Rosell-Ortiz F, Vandenberghe K, Regelin A, Bluhmki E, Bogaerts K, Van de Werf F. STEMI patients randomized to a pharmaco-invasive strategy or primary PCI: the STREAM 1-year mortality followup. Circulation 2014;130:1139 – 1145. 4. Vora AN, Holmes DN, Rokos I, Roe MT, Granger CB, French WJ, Antman E, Henry TD, Thomas L, Bates ER, Wang TY. Fibrinolysis use among patients requiring interhospital transfer for ST-segment elevation myocardial infarction care: a report from the US National Cardiovascular Data Registry. JAMA Intern Med 2015;175: 207 –215. 5. Terkelsen CJ, Sorensen JT, Maeng M, Jensen LO, Tilsted HH, Trautner S, Vach W, Johnsen SP, Thuesen L, Lassen JF. System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention. JAMA 2010;304: 763 –771. 6. Huber K, Gersh BJ, Goldstein P, Granger CB, Armstrong PW. The organization, function, and outcomes of ST-elevation myocardial infarction networks worldwide: current state, unmet needs, and future directions. Eur Heart J 2014;35: 1526 –1532. 7. Bosch X, Curo´s A, Argimon JM, Faixedas M, Figueras J, Jimeńez Fa`brega FX, Masia` R, Mauri J, Tresserras R. Modelo de intervencioń coronaria percutańea primaria en Catalunã. Rev Esp Cardiol 2011;11(Suppl.C):51 –60. 8. Carrillo X, Fernandez-Nofrerias E, Rodriguez-Leor O, Oliveras T, Serra J, Mauri J, Curos A, Rueda F, Garcıá-Garcıá C, Tresserras R, Rosasm A, Teresa Faixedas M, Bayes-Genis A. on behalf of the Codi IAM Investigators. Early ST elevation myocardial infarction in non-capable percutaneous coronary intervention centres: in situ fibrinolysis vs. percutaneous coronary intervention transfer. Eur Heart J 2016;37: 1034 –1040. 9. Claeys MJ, de Meester A, Convens C, Dubois P, Boland J, De Raedt H, Vranckx P, Coussement P, Gevaert S, Sinnaeve P, Evrard P, Beauloye C, Renard M, Vrints C. Contemporary mortality differences between primary percutaneous coronary intervention and thrombolysis in ST-segment elevation myocardial infarction. Arch Intern Med 2011;171:544 –549. 10. Danchin N, Puymirat E, Steg PG, Goldstein P, Schiele F, Belle L, Cottin Y, Fajadet J, Khalife K, Coste P, Ferrieres J, Simon T. Five-year survival in patients with ST-segment-elevation myocardial infarction according to modalities of reperfusion therapy: the French Registry on Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) 2005 Cohort. Circulation 2014;129:1629 –1636. 11. Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M, ESC Committee for Practice Guidelines (CPG). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. Eur Heart J 2008;29: 2909 –2945. 12. Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet 2006;367:569 –578.


Transporting STEMI patients for primary PCI: a long and winding

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