Acute Coronary Syndromes (ACS)

Acute coronary syndrome (ACS) refers to a range of acute myocardial ischaemic states, which include unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI).¹ This article refers mainly to unstable angina and NSTEMI. STEMI is discussed in separate articles on acute myocardial infarction. Acute coronary syndromes are now classified mainly on the findings on the admission electrocardiogram:²

• ST segment elevation acute coronary syndrome: ST segment elevation (suggestive of transmural ischaemia) is present. There is an indication for urgent reperfusion treatment, either by percutaneous coronary intervention or by administration of a thrombolytic agent.
• Non-ST segment elevation acute coronary syndrome: no ST segment elevations are present (normal or depressed ST segments or T wave inversion).
• If myocardial necrosis is documented, a discharge diagnosis of STEMI or NSTEMI is made. Whether myocardial infarction is present usually becomes clear at a later stage, on the basis of laboratory tests (elevation of markers such as creatine kinase MB or cardiac troponins) or on the electrocardiogram (loss of QRS voltage or development of pathological Q waves).
• Myocardial infarction may be subclassified as Q wave or non-Q wave myocardial infarction.
• If no evidence of myocardial necrosis exists, a discharge diagnosis of acute coronary syndrome or unstable angina is generally used.

• In the United Kingdom, about 114 000 patients with acute coronary syndromes are admitted to hospital each year.²

Risk factors

• Non-modifiable risk factors for atherosclerosis: increasing age, male, family history of premature coronary heart disease, premature menopause.
• Ethnic Group: In the UK, the highest recorded rates of coronary artery disease mortality are in people born in India, Pakistan and Bangladesh.³
• Modifiable risk factors for atherosclerosis: smoking, diabetes mellitus (and impaired glucose tolerance), hypertension, raised LDL cholesterol, reduced HDL cholesterol, obesity, inactivity.
• Consider non-atherosclerotic causes in younger patients or if there is no evidence of atherosclerosis: coronary emboli from sources such as an infected cardiac valve, coronary occlusion secondary to vasculitis, coronary artery spasm, cocaine use, congenital coronary anomalies, coronary trauma, increased oxygen requirement (e.g. hyperthyroidism) or decreased oxygen delivery (e.g. severe anaemia).

The presentation of unstable angina and NSTEMI may be indistinguishable, and also undistinguishable from acute STEMI. The distinction depends on the pattern of changes on the ECG and any increase in the biochemical markers of myocardial damage, e.g. troponins.

• Symptoms: chest pain, which may be associated with sweating, nausea, vomiting, dyspnoea, fatigue, or palpitations. Shortness of breath.
• Some patients, particularly the elderly and patients with diabetes, may not have chest pain.⁴ Patients from some ethnic groups may present with atypical pains.
• Signs: physical examination is focused on the assessment of cardiac function and circulatory stability and to exclude important differential diagnoses.

• Cardiovascular: ST segment elevation infarction, acute pericarditis, myocarditis, aortic stenosis, aortic dissection, pulmonary embolism
• Respiratory: pneumonia, pneumothorax
• Gastrointestinal: oesophageal spasm, oesophagitis, gastro-oesophageal reflux, acute gastritis, cholecystitis, pancreatitis
• Musculoskeletal chest pain

It is essential to exclude a myocardial infarction with ST elevation for which immediate thrombolysis is indicated.

• ECG:
  • To confirm a cardiac basis for presentation and may show pre-existing structural or ischaemic heart disease (e.g. left ventricular hypertrophy, Q waves).
  • A normal or unchanged ECG does not exclude the possibility that chest pain is ischaemic in origin.
  • Changes that may be seen during episodes of angina include transient ST segment elevations (fixed changes suggest acute infarction).
  • In unstable angina (and non-Q wave infarction) the ECG typically shows T wave inversion or ST segment depression, but the ECG may be normal if some time has elapsed since the last episode of pain.
• Cardiac enzymes:
  • Within the first 6 hours, the sensitivity of troponins is superior to CK-MB for the detection of myocardial infarction.
  • Troponin I and T become detectable in serum 3-6 hours after infarction, peak at 12-24 hours, and remain raised for up to 14 days.
  • Troponins are therefore usually tested 6 and 12 hours after the onset of pain.
  • In patients with unstable angina, minor troponin elevations may identify patients at risk for subsequent cardiac events and death. Elevated troponin levels indicate an increased risk of mortlaity in both the short term and long term. Patients with chest pain and elevated troponin levels should remain in hospital for further assessment, including an inpatient cornary angiogram.
• Full blood count may be useful in patients with suspected anaemia and as a baseline in view of use of anticoagulants; blood glucose, renal function and electrolytes, thyroid function tests. CRP as a marker of acute inflammation.
• Echocardiography often demonstrates wall motion abnormalities due to ischaemia. May be useful in identifying precipitants for ischaemia, e.g. ventricular hypertrophy and valvular disease.
• Chest x-ray may show complications of ischaemia, e.g. pulmonary oedema, or explore alternative diagnoses, e.g. pneumothorax, aortic aneurysm.

Recent trials have shown that, in high risk patients, early invasive strategy (percutaneous coronary intervention or coronary artery bypass surgery) produced a better outcome than non-invasive management.^3,5,6 However, in lower risk patients, conservative management (initial intensive medical treatment followed by non-invasive risk assessment, e.g. by exercise ECG) has been found to be as effective as early invasive management. Predictors of death in patients with acute coronary syndromes include:²

• Age
• Killip classification of degree of heart failure
• Heart rate
• Blood pressure
• ST deviation on electrocardiogram
• Cardiac arrest
• Raised creatinine
• Raised creatine kinase MB or troponin
• Clinical instability

TIMI (Thrombolysis in Myocardial Infarction) risk score⁷

The TIMI risk score is one method used to assess risk in patient with ACS. The TIMI risk score gives a score of 1 for each of the following:

• Age older than 65 years
• More than three coronary artery disease risk factors (hypertension, hyperlipidaemia, family history, diabetes, smoking)
• Known coronary artery disease
• Aspirin use in the last 7 days
• Severe angina (more than 2 episodes of rest pain in 24 hours)
• ST deviation on ECG > 1 mm
• Elevated cardiac markers (CK-MB) or troponin

The risk of myocardial infarction or death within 14 days increases with increased total score:

• Total score 0-2: 3% risk
• Score of 4: 7% risk
• Score of 6-7: 19% risk

Therefore the TIMI risk stratification score can inform triage decisionsis and is one method of identifying patients who require gylcoprotein IIb/IIIa inhibitor treatment and/or percutaneous coronary intervention (PCI). Patients with low scores (0 or 1) are at low risk of events and may potentially be safely discharged after measurement of an early cardiac marker, e.g. 6 hour troponin, combined with a period of observation or management in a chest pain unit.⁸ However the TIMI risk score should not be used in isolation to determine management of patients presenting with chest pain.⁹

The treatment of patients with non-ST segment elevation acute coronary syndrome is directed to alleviate pain and anxiety, prevent recurrences of ischaemia and prevent or limit progression to acute myocardial infarction. Treatment includes antithrombotic treatment, as well as coronary angiography followed by revascularisation if appropriate.²

• Antiplatelet agents: patients admitted with non-ST segment elevation acute coronary syndrome should be treated with oral aspirin and clopidogrel (see below). Low molecular weight heparins (e.g. enoxaparin) are the preferred anticoagulant.
  • Aspirin reduces the risk of complications by more than 50%.
  • Low molecular weight heparin: is also effective and the combination of heparin and aspirin is more effective than aspirin alone.
  • Clopidogrel- treatment within 24 hours has been shown to decrease cardiac death, myocardial infarction or stroke. Clopidogrel, in combination with low-dose aspirin, is recommended for use in the management of NSTEMI in people who are at moderate to high risk of myocardial infarction or death. Combination with low-dose aspirin should be continued for up to 12 months after the most recent acute episode of non-ST segment-elevation ACS and then low-dose aspirin alone is recommended.¹⁰
  • Glycoprotein IIb/IIIa receptor inhibitors, in addition to aspirin and unfractionated heparin, are recommended as part of the initial management of unstable angina or NSTEMI in those patients at high risk of subsequent myocardial infarction. Treatment should be started as soon as high risk status is determined. Glycoprotein IIb/IIIa inhibitors are recommended as an adjunct to PCI for all patients with diabetes, and for those patients undergoing complex procedures (e.g. multi-vessel PCI and insertion of multiple stents).¹¹
• Nitrates (sublingual, oral or intravenous): for ongoing pain whilst waiting for more definitive procedures and may overcome superimposed coronary artery spasm.
• Beta-blockers improve outcome and can reduce the severity and frequency of attacks.
• Calcium antagonists, e.g. diltiazem, verapamil, are used for patients who cannot tolerate a beta-blocker or in addition to a beta-blocker. Verapamil should not be combined with a beta-blocker.
• ACE inhibitor: reduce mortality and should be started as an inpatient unless contraindicated.
• An insulin sliding scale should be used for patients with diabetes mellitus or a raised blood glucose.
• Revascularisation:
  • There is debate as to whether all patients with non-ST segment elevation acute coronary syndrome should have coronary angiography followed by revascularisation (if indicated and if possible) or whether this should be done selectively in patients at high risk or in those who are refractory to medical treatment.²
  • Any patient with an elevated plasma concentration of troponin marker, ST segment changes, or haemodynamic instability should also undergo early angiography if available.
• After stabilisation, secondary risk reduction measures should be implemented. These measures include stopping smoking, continued aspirin therapy, management of hypertension if present, statins, ACE inhibitors and beta-blockers.⁶ If a patient was stabilised with medical treatment then it is likely they will undergo treadmill exercise testing.

Immediate management

• Call 999 - refer immediately to hospital¹²
• High concentration oxygen
• Pain relief with diamorphine or morphine with an anti-emetic as required
• Aspirin 300 mg orally (dispersible or chewed)
• Sublingual GTN

Management in accident and emergency

• Continue high flow oxygen
• Connect to cardiac monitor; monitor blood pressure and pulse rate
• 12 lead ECG
• Insert a venflon for intravenous access and take blood tests for full blood count, renal function and electrolytes, troponin, clotting screen, glucose, lipids, clotting screen, CRP
• Further pain relief: try further GTN or opiate with or without an anti-emetic
• History and examination, and review 12 lead ECG; consider clopidogrel, low molecular weight heparin, thrombolysis or urgent PCI
• Further pain relief – infusion of GTN or further opiates
• Start beta blocker (ideally short acting e.g. metoprolol) or rate-limiting calcium channel blocker (review BP
• Start insulin sliding scale if patient has diabetes mellitus or raised capillary blood sugar
• Admit to coronary care unit

Management in coronary care unit

No pain:
• Continue monitoring, aspirin, clopidogrel, LMWH, beta blocker or rate limiting calcium channel blocker
• Start ACE inhibitor (check renal function and potassium)
• Start a statin
• Continue insulin sliding scale if started
• Ongoing pain:
  • GTN infusion or further opiates
  • Repeat 12 lead ECG: if evidence of ischaemia, commence glycoprotein IIb/IIIa receptor inhibitor and discuss with local PCI unit
  • Continue monitoring, aspirin, clopidogrel, low molecular weight heparin, beta blocker or rate limiting calcium channel blocker
  • Start ACE inhibitor (check renal function and potassium)
  • Start statin
  • Continue insulin sliding scale if started
• If patient settles – and troponin positive – cardiology review as an inpatient
• If patient fails to settle, regardless of troponin, consider for urgent PCI
• If patient settles and troponin negative, this does not rule out cardiac disease and patients should be referred for outpatient cardiology follow-up (especially if no cause for the chest pain was determined). However, if the history is very suspicious patients should have inpatient cardiac review.

• Acute myocardial infarction
• Cardiogenic shock
• Ischaemic mitral regurgitation
• Supraventricular arrhythmias: rare complication of ischaemia but may precipitate ischaemic events
• Ventricular arrhythmias: simple and complex premature ventricular contractions and non-sustained ventricular tachycardia
• Atrioventricular nodal blockade: usually transient in setting of reversible ischemia (treatment is guided by location of block and haemodynamic stability)

In-hospital death and re-infarction affect 5-10%. Despite optimal treatment with anti-ischaemic and antithrombotic drugs, death and recurrent myocardial infarction occur in another 5-10% of patients in the month after an acute episode. Several studies indicate that these patients may have a higher long-term risk of death and myocardial infarction than do patients with ST segment elevation. Factors associated with a poorer prognosis in unstable angina include the following:

• Evidence of myocardial necrosis, as determined by elevated troponins
• Delays in angiography in patients at high risk

Primary cardiovascular disease prevention and secondary cardiovascular disease prevention.

• Smoking cessation
• Dietary and exercise advice
• Blood pressure, hyperlipidaemia and diabetes control
• Compliance with medications, particularly aspirin
• Comprehensive risk assessment including exercise tolerance test for those at high risk and identification of structural heart disease (e.g. left ventricular hypertrophy, aortic stenosis)