Update on Acute Coronary Syndromes

Introduction: The 2023 European Society of Cardiology (ESC) Guidelines for the management of acute coronary syndromes (ACS) were released at the annual ESC conference in Amsterdam this year. For the first time, all of ACS was covered in one document. This includes ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) and Unstable Angina (UA). This allowed the guideline to highlight the common principles underpinning the identification, diagnosis, and treatment of patients with all three subtypes of ACS. A key aspect of the guideline was the concept that ACS can be best considered as a spectrum. In this article, we will highlight some of the most important messages from the guideline, many of which are summarised in Figure 1

ACS Terminology

The guideline aimed to make the terminology used to describe ACS clear. ACS includes patients presenting with both myocardial infarction (MI) and UA. MI is defined as per the fourth universal definition of MI (UDMI) and is associated with elevations in cardiac biomarkers. In modern practice, high sensitivity cardiac troponin (hs-cTn) is the recommended biomarker to use. The fourth UDMI sub-categorises MI into five categories, as per the aetiology. This is summarised in Table 1

The 2023 ESC ACS guideline is primarily focused on the management of patients with type 1 MI, which is related to a primary coronary plaque event (most commonly plaque rupture or erosion). This is sometimes referred to as a ‘spontaneous MI’. UA is not associated with elevated cardiac biomarkers but is defined clinically as myocardial ischaemia at rest or on minimal exertion in the absence of acute cardiomyocyte injury/necrosis. It is characterized by specific clinical findings of prolonged (>20 min) angina at rest; new onset of severe angina; angina that is increasing in frequency, longer in duration, or lower in threshold; or angina that occurs after a recent episode of MI.

The common underlying pathophysiology in all three conditions (UA, NSTEMI, STEMI) is thought to be unstable coronary plaque in the majority of cases. This explains why the management of all three conditions shares many common features, particularly after the initial treatment phase.

Initial Classification

The initial classification of ACS is based on the clinical presentation and the ECG. Patients presenting with symptoms suggestive of ACS can be classified as STEMI or NSTE-ACS based on the presence or absence of ST segment elevation (or equivalents) on ECG. It should be noted that the presence of ST elevation on ECG is a surrogate marker for an occluded artery. Like any diagnostic tool, this is imperfect and patients may have an occluded artery without demonstrating ST elevation on ECG. Other ECG patterns that may prompt triage for immediate angiography include ST depression in V1-V3 (posterior STEMI) and widespread ST depression in 6 or more leads coupled with ST elevation in aVR and/or V1. Recognition of these ECG patterns is important as patients with STEMI should be treated with primary percutaneous coronary intervention (PPCI) as soon as possible. If PPCI cannot be performed within 120 minutes, fibrinolysis can be used as an alternative treatment.

Patients with suspected NSTE-ACS and very high-risk criteria should also be treated with immediate angiography ± percutaneous coronary intervention (PCI) if indicated. These very high-risk criteria include any of the following: haemodynamic instability or CS, recurrent or refractory chest pain despite medical treatment, life-threatening arrhythmias, mechanical complications of MI, HF clearly related to ACS, and recurrent dynamic ST-segment or T wave changes, particularly with intermittent ST-segment elevation. For patients with NSTE-ACS and high risk criteria (confirmed diagnosis of NSTEMI as per ESC algorithms, GRACE risk score >140, transient ST segment elevation or dynamic ST or T wave changes), an early invasive angiography approach should be considered and inpatient invasive angiography is recommended. For some patients with a low index of suspicion for invasive angina, a selective invasive strategy may be considered. The definitions of the invasive strategies used in the guideline are provided in Table 2.

A crucial part of the early management of patients with ACS is the early identification of patients with STEMI and very high risk NSTE-ACS and ensuring that they are treated appropriately. The invasive management of patients with STEMI and NSTE-ACS is summarised in Figure 2 and Figure 3

Diagnostic algorithms for NSTEMI

For patients who do not require immediate invasive management, it is recommended to use an algorithmic approach to rule in/ rule out NSTEMI. The guidelines recommend that the 0/1 hr or 0/2 hr ESC algorithms are used for this. The algorithms are troponin assay specific, but the general principle is the same; using two hs-cTn measurements (taken at the time of arrival to the ED and 1/2 hours later), we can rapidly stratify patients with suspected NSTEMI into one of three groups, rule in, observe or rule out. While there are several caveats to the use of these algorithms, they facilitate the early identification of patients with NSTEMI and are recommended. All centres should use these algorithms as a key component of their assessment of patients with suspected ACS and this is highlighted in Figure 4

Antithrombotic therapy

All patients with ACS should be treated with antithrombotic therapy, which consists of a combination of antiplatelet therapy and anticoagulant therapy. For patients who do not have an indication for long term anticoagulation (i.e., atrial fibrillation or a mechanical heart valve), anticoagulation will not need to be continued beyond the acute phase of the ACS. However, antiplatelet therapy should be continued beyond the acute phase after ACS in all patients.

Anticoagulation

Anticoagulation is recommended for all patients with ACS at the time of diagnosis. The most well established anticoagulant option for patients with ACS is unfractionated heparin (UFH) and this has a class I recommendation for patients at the time of PCI. For patients with STEMI, alternatives to UFH which should be considered include low molecular weight heparin (LMWH) and bivalirudin, a direct thrombin inhibitor. For patients with NSTEACS, the recommendations for anticoagulation are dependent on the period of time from diagnosis to angiography. For patients with intended angiography within 24 hours, LMWH should be considered as an alternative to UFH. For patients with an anticipated delay to angiography > 24 hours, fondaparinux (a synthetic pentasaccharide factor Xa inhibitor) is recommended. For patients without an indication for long term anticoagulation, the anticoagulant drug can generally be stopped after the invasive procedure is performed.

Antiplatelet therapy

Dual antiplatelet therapy (DAPT) is indicated for patients with ACS and consists of aspirin and a P2Y12 inhibitor. Available P2Y12 inhibitors include prasugrel, ticagrelor and clopidogrel. It is recommended that patients who are not at high bleeding risk (HBR) receive 12 months of DAPT. Prasugrel and ticagrelor are recommended in preference to clopidogrel and prasugrel should be considered in preference to ticagrelor in patients who are undergoing PCI.

Alternative strategies to 12-month DAPT include DAPT abbreviation and DAPT de-escalation. DAPT abbreviation refers to shortening the duration of DAPT, followed by single antiplatelet therapy (SAPT), which can consist of aspirin or P2Y12 inhibitor monotherapy.

This should be considered in patients who are event free after 3-6 months of DAPT and may be considered after 1 month of DAPT in patients at HBR.

DAPT de-escalation refers to switching from prasugrel or ticagrelor based DAPT to clopidogrel based DAPT and this may also be considered. It should be stressed that these are viewed as alternative strategies in the guideline and should only be employed where there is a clear motivation/rationale for their use, as opposed to being indiscriminately utilised in the wider ACS population. HBR can be defined using the Academic Research Consortium (ARC) HBR criteria, as summarised in Table 3. Patients who meet 1 major criterion or ≥2 minor criteria are considered HBR.

Routine pretreatment with P2Y12 inhibitors (defined as a strategy in which the P2Y12 inhibitor is given before coronary angiography and, therefore, before the coronary anatomy is known) is not recommended in patients with NSTE-ACS who are scheduled for early (<24 h) invasive angiography but may be considered in patients with STEMI undergoing PPCI and in patients with NSTE-ACS who are not scheduled for early invasive coronary angiography and who are not HBR. Parenteral anticoagulation and loading with aspirin are both recommended at the time of diagnosis for patients with ACS.

Long Term Treatment

Patients who have experienced an ACS event are at a high risk of future cardiovascular events and so require long term treatment to try to reduce this risk. As discussed in the previous section, antiplatelet therapy is an important component of the long-term medication regimen for ACS patients. All patients with ACS should also be treated with lipid lowering agents and the initiation and escalation of the recommended lipid lowering agents (statins, ezetimibe and proprotein convertase subtilisin/ kexin type 9 [PCSK9] inhibitors) should follow the treatment algorithm outlined in Figure 5

Promotion of healthy lifestyle choices is essential, including smoking cessation, adoption of a healthy diet, regular exercise, achieving a healthy weight and management of psychosocial factors. All patients should undergo a structured cardiac rehabilitation program where they can be educated on these topics. Risk factor treatment targets are also important, including BP (systolic <130mmHg and diastolic <130mmHg) and low-density lipoprotein (<1.4mmol/L).

Patients with ACS and Cancer

This guideline included a dedicated section on the management of patients with ACS and cancer. Cancer and atherosclerotic cardiovascular disease share many common risk factors. More patients with cancer are surviving and so there are an increasing number of patients presenting with ACS who either have a history of cancer or are undergoing active treatment for cancer. While patients with a history of cancer should be treated similarly to all patients to ACS, patients with active cancer and ACS have some specific considerations that should be taken into account. Some cancer therapies can be associated with ACS. If a cancer therapy is suspected as being a contributing cause of the ACS presentation, this is recommended to be interrupted. It is important that a multi-disciplinary teambased approach is adopted when managing these patients. If patients with cancer and ACS have an expected survival of > 6 months, then an invasive strategy is recommended. However, if the cancer related prognosis is poor (i.e., < 6 months), a conservative approach should be considered.

Patient perspectives

For the first time, a section on patient perspectives was included in this ACS guideline. This section highlights that care of patients with ACS should not only strive to employ the most evidence-based practices but should also try to promote care that is respectful of, and responsive to, the individual patients’ preferences, needs and values. This is an important concept for all healthcare professionals involved in the care of patients with ACS to reflect upon. It is always important to consider what is important to the patient and to involve the patient as much as possible in clinical decision making.

Summary

The 2023 ESC Guidelines for the management of ACS covers the whole spectrum of ACS in one guideline for the first time. One of the underlying principles for the guideline was to try to highlight the commonalities in the management of patients with UA, NSTEMI and STEMI. Early identification, diagnosis and risk stratification of ACS allows for appropriate management strategies to be employed. Patients with ACS should receive treatment with antiplatelet therapy and anticoagulation, undergo invasive assessment and revascularisation. After the acute phase, it is important that long term treatment focuses on optimisation of cardiovascular risk, in order to reduce the risk of recurrent events. It is also important to practice patient centred care throughout the ACS journey, from the time of first medical contact through to long term management. It is hoped that the 2023 ESC Guidelines will assist healthcare providers in delivering optimal care to patients with ACS worldwide. More information can be obtained from the full guideline, available free of charge on the ESC website. https://www.escardio. org/Guidelines/Clinical-PracticeGuidelines/Acute-CoronarySyndromes-ACS-Guidelines

Written by:

J.J. Coughlan and Robert A. Byrne

Affiliations:

1. Cardiovascular Research Institute, Mater Private Network, Eccles Street 73, Dublin 7, D07 WKW8, Ireland

2. School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland

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