Author: Jason M Kendall / Editor: Tajek B Hassan, Jon Bailey / Reviewer: Stewart McMorran / Codes: CC1, CC2, CP1, SLO1 / Published: 01/05/2023

Acute Coronary Syndromes (ACS) encompass a broad range of presentations including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Understanding the pathophysiology, classification and clinical presentation of ACS is a pre-requisite for effective risk stratification and treatment. The chart shows the classification of ACS.

Myocardial infarction (MI) is defined pathologically as myocardial cell death following prolonged ischaemia [1]. In the context of cardiac marker rise, ST-segment changes on the ECG will define either STEMI or NSTEMI. At the time of presentation, however, cardiac marker status is unknown and classification of patients presenting with ischaemic chest pain is based largely on the ECG. Most patients with ST elevation progress to STEMI; their management is the subject of a separate Learning Session.

Many patients without ST elevation may not have a subsequent cardiac marker rise and are collectively termed non-ST-segment elevation acute coronary syndromes (ACS) at presentation; subsequently, their markers will define them as non-STEMI (marker rise) or UA (no marker rise) [2]. Risk stratification and management of ACS is the subject of this session.


Patients with ACS are a heterogeneous population with varying degrees of atherosclerotic disease and thrombotic risk and, therefore, varying mortality and recurrent cardiac event rates. In order to select the most appropriate treatment, early and repeated risk stratification should be performed since the benefit from certain aggressive treatment strategies is related to risk – the higher the risk, the greater the benefit.

As per NICE, as soon as the diagnosis of unstable angina or NSTEMI is made, and aspirin and antithrombin therapy have been offered, formally assess individual risk of future adverse cardiovascular events using an established risk scoring system that predicts 6‑month mortality (for example, Global Registry of Acute Cardiac Events [GRACE]) [3].

A formal risk assessment should include a full clinical history (including age, previous myocardial infarction [MI] and previous PCI or coronary artery bypass grafting [CABG]), a physical examination (including measurement of blood pressure and heart rate), a resting 12‑lead ECG, looking particularly for dynamic or unstable patterns that indicate myocardial ischaemia, blood tests (such as troponin I or T, creatinine, glucose and haemoglobin).

Thrombolysis in Myocardial Infarction (TIMI)

Several risk stratification ‘scores’ are available and are based on clinical history, ECG findings and cardiac markers [3-5]. One of the most widely used is the Thrombolysis in Myocardial Infarction (TIMI) risk score [3-5]. It estimates 30 day mortality for patients with UA and NSTEMI. Although it can be used for patients with anginal symptoms, it is better suited for patients with confirmed NSTEMI or UA.

What are the components of the TIMI risk score?

The TIMI risk score is composed of seven independent predictor variables, each carrying a similar prognostic weight, shown in the table. The risk score is calculated as a simple arithmetic sum of the number of predictors that apply to an individual patient.

Elements of the TIMI

The TIMI risk score was designed, developed and validated in cohorts with patients with ACS [3-5]. It is useful to determine prognosis and treatment. The higher the score, the higher the adverse event rate. See Fig 1 for the prognostic value of the TIMI risk score.

Fig 1

The TIMI risk score can also identify patients that will benefit from certain interventions (e.g. Glycoprotein IIb/IIIa Receptor Inhibitors (GpIIb/IIIa Inhibitors) and early percutaneous coronary intervention): the higher the risk, the greater the benefit from these interventions. See Fig 2 for the TIMI risk score and Tirofiban (GpIIb/IIIa Inhibitor) benefit.

Fig 2

Learning bite

In contrast to patients with STEMI, risk stratification in patients with NSTE-ACS not only determines prognosis but also directly influences early treatment options.

Global Registry of Adverse Cardiac Events (GRACE)

NICE recommends the GRACE Score for risk stratification because it is based on a very large (and growing) cohort of registry patients and gives robust mortality figures. The GRACE (Global Registry of Adverse Cardiac Events) score [4] also uses accessible factors but it is slightly more complicated to use than the TIMI risk score and requires computer software or a nomogram. It estimates 6 month mortality and like TIMI, is best suited to patients with known STEMI or NSTEMI. It is recommended by NICE for risk stratification of ACS [6]. The parameters are entered into the risk tool and the mortality figures are calculated by the nomogram. It is slightly less convenient to use in the ED than the TIMI score because it requires two blood assay results to complete the assessment (creatinine and troponin) and a computer to generate the risk.

Six month mortality and level of risk Table 1

1.5% or below Lowest
>1.5 – 3% Low
>3% – 6% Intermediate
>6% – 9% High
Over 9% Highest

Treatment strategies (pharmacological and mechanical) are then recommended by NICE based on the level of risk as determined by GRACE (see later in the session).


  • The Emergency Department Assessment of Chest Pain (EDACS) identifies patients with chest pain that have a low risk of a major adverse cardiac event (MACE) [7].
  • It is used for patients with normal vital signs, chest pain consistent with ACS, and with pain that is no longer ongoing.
  • It considers Age, Sex, the presence of known coronary artery disease or more than 3 risk factors, and clinical presentation.
  • EDACS enables the identification of low risk patients for outpatient care or discharge.
  • Patients identified to not be at low risk are admitted and managed on conventional cardiac chest pain pathways [20].


  • The HEART (History ECG Age Risk factors Troponin) score was developed for undifferentiated patients with possible ACS [21].
  • It considers history [8], ECG findings, age, risk factors and initial troponin.
  • Low risk patients have a 0.9 – 1.7% 6 week risk of a Major Cardiac Event (MACE). After a repeat 3 hour negative troponin, they can be discharged with outpatient follow up.
  • High risk patients require admission and serial assessment [21].

ACS are essentially due to an imbalance between coronary supply and myocardial demand of oxygen and nutrients.

Therapy (pharmacological and interventional) is aimed at redressing this imbalance.

Pharmacological treatment can be divided into anti-thrombotic and anti-ischaemic:

  • Anti-thrombotic agents inhibit intracoronary thrombosis through effects on the clotting cascade or via anti-platelet mechanisms
  • Anti-ischaemic agents decrease myocardial oxygen demand through negative inotropic or chronotropic actions or through vasodilation

The image shows the reduction of blood supply to the myocardium caused by varying degrees of coronary occlusion.

General Measures – ‘Cardiac First Aid’

NICE recommends offering aspirin as soon as possible to all people with unstable angina or non‑ST‑segment elevation myocardial infarction (NSTEMI) and continue indefinitely unless contraindicated by bleeding risk or aspirin hypersensitivity. This should initially be a loading dose of 300mg aspirin, followed by 75mg once daily.  The only contraindication to the initial loading dose is clear evidence of allergy [3].

Patients should be offered opiate analgesia (morphine or diamorphine) and should be given supplementary oxygen to a target saturation level of >93%.  Excessive oxygen can increase infarct size, and should be avoided.  GTN should also be offered as adjunctive analgesia. It is also important to avoid uncontrolled hyperglycaemia.  Manage hyperglycaemia in people admitted to hospital for an acute coronary syndrome by keeping blood glucose levels below 11.0 mmol/litre while avoiding hypoglycaemia. In the first instance, consider a dose-adjusted insulin infusion with regular monitoring of blood glucose levels.

Patients should be offered immediate coronary angiography if they have a diagnosis of unstable angina or NSTEMI if their clinical condition is unstable.

Coronary angiography (with follow‑on PCI if indicated) should be considered within 72 hours of first admission for people with unstable angina or NSTEMI who have an intermediate or higher risk of adverse cardiovascular events (predicted 6‑month mortality above 3.0%) and no contraindications to angiography (such as active bleeding or comorbidity).  A decision not to proceed to PCI should be revisited if patients develop ongoing symptoms, or in young patients with falsely reassuring low risk scores.

Table 1 [3] Benefits and risks of early invasive treatment (coronary angiography with PCI if needed) compared with conservative management for people with unstable angina or NSTEMI

Benefits/risks/other factors Coronary angiography and possible percutaneous coronary intervention (PCI) within 72 hours Conservative management with later coronary angiography if problems continue or develop
Benefits (advantages)

Reduced deaths from all causes at 6 to 12 months and at 2 years.

Reduced deaths from heart problems at 1 and 2 years. Reduced incidence of myocardial infarction (MI) at 30 days, 6 to 12 months and 2 years.

Reduced incidence of stroke at 1 year, particularly in people at high risk of future adverse events.

Reduced readmission to hospital and difficult-to-treat angina in the medium term, particularly in people at high risk of future adverse events.

Psychological benefits – people are not anxious about delaying angiography.

Avoid the immediate risks of invasive treatment, including:

  • death within 4 months related to the procedure from causes other than MI
  • procedure-related MI
  • major bleeding in hospital and up to 2 years after the procedure.

These are particularly relevant for people at low risk of future adverse events.

Psychological benefits – people are not anxious about having an invasive procedure.

Risks (disadvantages)

Increased risk of death during the first 4 months, particularly for people at low risk of future adverse events.

Risk of procedure-related MI.

Increased risk of major bleeding during the index admission, at 30 days and 2 years.

Emergency treatment leaves little time for shared decision making.

Increased risk of MI after 6 months.

Increased risk of stroke at 1 year, particularly in the people at high risk of future adverse events.

Psychological factors – people may be anxious about delaying angiography.

Other factors

Recent advances in PCI might increase early benefit, particularly reducing bleeding.

Coronary angiography within 72 hours ensures speedy intervention while allowing time for the correct diagnosis, identifying other conditions and treating symptoms.

Learning bite

Early angiography and subsequent revascularisation should be considered alongside comprehensive anti-ischaemic and anti-thrombotic therapy for intermediate and high risk patients.

The choice of antiplatelet agents is dictated by mechanical intervention. Firstly, offer fondaparinux to people with unstable angina or NSTEMI who do not have a high bleeding risk, unless they are undergoing immediate coronary angiography.

When PCI is not indicated, offer ticagrelor as part of dual antiplatelet therapy with aspirin, to people with unstable angina or NSTEMI when PCI is not indicated, unless they have a high bleeding risk. Consider clopidogrel, as part of dual antiplatelet therapy with aspirin, or aspirin alone, for people with unstable angina or NSTEMI when PCI is not indicated, if they have a high bleeding risk.

When PCI is indicated, offer systemic unfractionated heparin in the cardiac catheter laboratory to people with unstable angina or NSTEMI who are undergoing PCI whether or not they have already received fondaparinux. In patients with significant renal impairment unfractionated heparin can be used as a substitute for fondaparinux. Furthermore, offer prasugrel or ticagrelor, as part of dual antiplatelet therapy with aspirin, if they have no separate indication for ongoing oral anticoagulation.

Clopidogrel, as part of dual antiplatelet therapy with aspirin, if they have a separate indication for ongoing oral anticoagulation.

For secondary prevention, offer people who have had MI treatment with the following drugs:

angiotensin-converting enzyme (ACE) inhibitor. Titrate the ACE inhibitor dose upwards at short intervals (for example, every 12 to 24 hours) before the person leaves hospital until the maximum tolerated or target dose is reached.

Dual antiplatelet therapy (aspirin plus a second antiplatelet) unless they have a separate indication for anticoagulation.


Consider continuing a beta-blocker for 12 months after an MI for people without reduced left ventricular ejection fraction. Discuss the potential benefits and risks of stopping or continuing beta-blockers beyond 12 months after an MI for people without reduced left ventricular ejection fraction. There is a lack of evidence on the relative benefits and harms of continuing beyond 12 months.  If beta-blockers are contraindicated, verapamil or diltiazem (rate limiting calcium channel blockers) can be considered instead.  Otherwise, do not routinely offer calcium channel blockers to reduce cardiovascular risk after an MI.


Ensure that a clear management plan is available to the person who has had an MI and is also sent to the GP, including:

  • Details and timing of any further drug titration
  • Monitoring of blood pressure
  • Monitoring of renal function.
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