Treatment patterns of non-ST-elevation acute coronary syndrome patients presenting at non-PCI centres in the Netherlands and possible logistical consequences of adopting same-day transfer to PCI centres: a registry-based evaluation

Non-ST-elevation acute coronary syndrome (NSTE-ACS) encompasses a clinical syndrome caused by superimposed thrombus formation due to intracoronary plaque rupture or erosion [1]. Coronary angiography is used to confirm obstructive coronary artery disease and select treatment with percutaneous coronary intervention (PCI), coronary bypass artery grafting (CABG), or medical therapy alone [1]. The European Society of Cardiology (ESC) recommends immediate angiography (<2 h) in patients at very high risk for mortality (ESC-VHR) (e. g. recurrent refractory angina, life-threatening arrhythmia or cardiogenic shock and haemodynamic instability) [1]. Early angiography is recommended in high-risk patients (ESC-HR) presenting with a rise or fall in high-sensitivity cardiac troponin (hs-cTn), or dynamic ST- or T‑wave changes, or a Global Registry of Acute Coronary Events (GRACE) risk score >140 points. In intermediate-risk patients (ESC-IR) the guidelines advise to undergo angiography within 72 h In low-risk patients (ESC-LR), a non-invasive ischaemia detection test is recommended.

Various randomised trials support the use of an early invasive strategy with angiography within 24 h [2, 3]. However, other studies could not demonstrate a benefit of an early invasive strategy versus a more ischemia-driven selective invasive strategy, including patients with elevated cardiac troponin levels [4]. Moreover, recent meta-analyses of contemporary randomised trials could not establish an association between an early invasive strategy and hard clinical outcomes, compared with a delayed strategy [5, 6].

Compared with the 2011 guidelines, the 2015 NSTE-ACS guidelines put more emphasis on same-day transfer to a PCI centre in patients with at least one high-risk criterion (e. g. elevated hs-cTn [2015 NSTE-ACS guidelines, Fig. 6]) [1, 7]. Both the 2011 and 2015 guidelines recommend ‘timely transfer for patients admitted to hospitals without on-site catheterisation facilities’ [1]. However, the guidelines do not specifically comment on ESC-HR patients presenting at non-PCI centres with on-site catheterisation facilities.

In the Netherlands, the majority of non-PCI centres are equipped with chest pain units, cardiac care units, and catheterisation laboratories where NSTE-ACS patients often undergo angiography. Angiographic results are discussed in a Heart Team and, if indicated, patients are referred to an interventional centre for PCI or CABG procedures.

The members if the ACS Working Group of the Netherlands Society of Cardiology (NVVC) remain concerned over the adoption of same-day transfer to PCI centres. They suggested that adoption of same-day transfer may increase transfers of patients with hs-cTn elevation due to type 2 myocardial infarction (MI) or other cardiac and non-cardiac aetiologies [8]. In addition, the possible logistical consequences of adopting same-day transfer for ambulance services and PCI and non-PCI centres remain unclear. The objective of this study was to describe the current treatment patterns (not the outcomes) of NSTE-ACS patients presenting at non-PCI centres in the Netherlands and evaluate the possible logistical consequences of adopting same-day transfer in clinical practice.

In this registry of NSTE-ACS patients presenting at 23 non-PCI centres in the Netherlands, we found that the majority of patients (55.8%) were classified as ESC-HR, mostly based on elevated hs-cTn levels. Our findings highlight that angiography of ESC-HR NSTE-ACS patients at non-PCI centres is still common (51.4%) and same-day transfer to a PCI centre only occurs in one-quarter of the ESC-HR patients, despite guideline recommendations. The revascularisation rate in ESC-HR patients was 54.9%. Assuming patients would receive similar treatment as observed in this registry, adopting same-day transfer of ESC-HR NSTE-ACS patients presenting at non-PCI centres would lead to an increase of transfers of patient who undergo PCI. However, this would also result in at least an equal number of transfers of NSTE-ACS patients treated with medical therapy alone.

The optimal timing of angiography and revascularisation in NSTE-ACS has been extensively studied. Since NSTE-ACS is a heterogeneous condition, the expected benefit from early angiography depends greatly on the severity of the symptoms and the patient’s risk profile. Therefore, timing of angiography is based on risk stratification [1]. The recommendation of same-day transfer aims to minimize the delay of angiography (and revascularisation) in ESC-HR NSTE-ACS patients. The 2015 guidelines put more emphasis on same-day transfer of ESC-HR patients to a PCI-centre, compared with earlier guidelines [1]. However, both the 2011 and 2015 ESC NSTE-ACS guidelines are largely based on the same studies [1, 3, 7, 10‐13]. In addition, two more studies were added to support the 2015 guidelines [14, 15]. Although various studies cited by the guidelines could not prove a benefit on hard clinical endpoints with an early invasive strategy (<24 h), early angiography did reduce recurrent ischaemia and shorten length of hospitalisation [13].

Our findings show that among non-transferred and transferred ESC-HR patients, patients who were directly transferred to a PCI centre had higher rates of immediate angiography (<2 h) and revascularisation. Additionally, they were less often discussed by a Heart Team compared with non-transferred ESC-HR patients. This may indicate that the attending physician at the non-PCI centre used clinical assessment, beyond ESC risk stratification, to refer some ESC-HR patients for immediate angiography (possibly followed by PCI) at a PCI centre and considered other ESC-HR patients for angiography at a non-PCI centre. Please note, non-transferred patients were significantly older than transferred patients.

Based on the treatment patterns in our registry and assuming similar treatment, 44.3% of ESC-HR patients underwent PCI. If non-selective same-day transfer of ESC-HR patients were to be adopted, there would be an additional 27% of transfers to a PCI centre of patients who undergo PCI. On the other hand, 36.2% of ESC-HR patients were medically treated and may have a similar benefit of receiving optimal medical therapy either at a non-PCI centre or a PCI centre. It raises the question whether the potential pros of same-day transfer outweigh the cons.

We believe the ideal timing (and location) of angiography in ESC-HR NSTE-ACS patients, needs to be determined in a randomised trial that involves hs-cTn assays, radial artery access, drug-eluting stents, and novel P2Y12 inhibitors. For now, identifying the NSTE-ACS patients who might benefit from early angiography and same-day transfer remains important. A registry of 1,500 ESC-HR NSTE-ACS patients with elevated hs-cTn levels without additional risk factors admitted to German chest pain units, showed similar rates of death, MI, or stroke at 4 months if patients were treated with either medical therapy, PCI <24 h, or PCI >24 h [16]. In the same study ESC-HR NSTE-ACS patients who were at a higher risk (e. g. GRACE score >140), PCI was associated with improved outcomes compared with conservative treatment. Although these results are merely hypothesis-generating, it suggests research should focus on selecting the right patients for same-day transfer, rather than non-selectively adopting same-day transfer of patients with elevated hs-cTn levels.

Currently, the attending physician at a non-PCI centre triages patients who present with chest pain suspected for NSTE-ACS. Several studies were conducted to evaluate pre-hospital triage of patients with suspected NSTE-ACS [17, 18]. Point-of-care troponin T testing by paramedics appears to be feasible [19]. In the NONSTEMI trial, pre-hospital troponin testing was used to diagnose NSTE-ACS, whether immediate or delayed angiography after point-of-care troponin testing benefits outcomes remains to be determined [18]. The FamouS Triage study used the modified HEART score including point-of-care hs-cTn testing in the pre-hospital setting. Patients with a modified HEART score of 0–3 did not develop any events during follow-up and could be safely ruled-out for MI by ambulance personnel [20]. The role of computerised tomography (CT) coronary angiography in NSTE-ACS patients will be further determined in the RAPID-CTCA study, which compares early CT coronary angiography with standard care with invasive angiography in 2,500 patients with suspected NSTE-ACS and elevated hs-cTn levels [21]. The first results are expected in 2019.

In this registry of NSTE-ACS patients at non-PCI centres, most ESC-HR patients underwent angiography at a non-PCI centre and same-day transfer occurred in one-quarter of the ESC-HR patients, despite guideline recommendations. Non-selective adoption of same-day transfer to a PCI centre would increase the number of transfers of ESC-HR patients who undergo PCI, however, equally increases the number of transfers of ESC-HR patients who are medically treated. A randomised trial in a contemporary setting is warranted to determine the benefit of early angiography (and same-day transfer) in NSTE-ACS patients with elevated hs-cTn levels.