Epidemiology

See also separate article Epidemiology of Coronary Heart Disease.

• The diagnosis of NSTEMI is more difficult to establish than STEMI and therefore its prevalence is harder to estimate.^[2]
• The annual incidence of hospital admissions for non-ST elevation ACS is about 3 per 1,000.^[2]
• In the UK, about 114,000 patients with acute coronary syndromes are admitted to hospital each year.^[1]

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, dyslipidaemia (raised low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol), obesity, physical inactivity.
• Consider nonatherosclerotic 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 (eg, hyperthyroidism) or decreased oxygen delivery (eg, severe anaemia).

Presentation

• The presentation of unstable angina and NSTEMI may be indistinguishable, and also indistinguishable from acute STEMI. NSTE-ACS can present in a variety of ways, including:^[2]
  • Prolonged (longer than 20 minutes) anginal pain at rest.
  • New-onset angina with limitation of daily activities.
  • Recent destabilisation of previously stable angina, with moderate or severe limitation of daily activities.
  • Post-myocardial infarction angina.
• Chest pain may be associated with sweating, nausea, vomiting, dyspnoea, fatigue, shortness of breath and palpitations.
• Some patients, particularly the elderly and patients with diabetes, may not have chest pain.^[4] Patients from some ethnic groups may also present with atypical pains.
• Physical examination is focused on the assessment of cardiac function and circulatory stability and on excluding important differential diagnoses.

Assessment for possible acute coronary syndrome^[5]

• Consider the history of the pain, any cardiovascular risk factors, history of ischaemic heart disease and any previous treatment, and previous investigations for chest pain.
• Symptoms that may indicate ACS include:
  • Pain in the chest and/or other areas (eg, the arms, back or jaw) lasting longer than 15 minutes.
  • Chest pain with nausea and vomiting, marked sweating and/or breathlessness, or haemodynamic instability.
  • New-onset chest pain, or abrupt deterioration in stable angina, with recurrent pain occurring frequently with little or no exertion and often lasting longer than 15 minutes.
• The response to glyceryl trinitrate (GTN) should not be used to make a diagnosis and symptoms should not be assessed differently in men and women or among different ethnic groups.

Differential diagnosis

• 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.

Investigations

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

• 12-lead ECG:
  • To confirm a cardiac basis for presentation and may show pre-existing structural or ischaemic heart disease (eg, 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 mortality 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 coronary angiogram.
• FBC may be useful in patients with suspected anaemia and as a baseline in view of use of anticoagulants; blood glucose, renal function and electrolytes, and TFTs. CRP as a marker of acute inflammation.
• Blood glucose: hyperglycaemia is common in people admitted to hospital with ACS. Hyperglycaemia at the time of admission with ACS is a powerful predictor of poorer survival and increased risk of complications while in hospital, regardless of whether or not the patient has diabetes.^[6]
• Echocardiography often demonstrates wall motion abnormalities due to ischaemia. May be useful in identifying precipitants for ischaemia - eg, ventricular hypertrophy and valvular disease.
• CXR may show complications of ischaemia - eg, pulmonary oedema, or explore alternative diagnoses - eg, pneumothorax, aortic aneurysm.
• Cardiac magnetic resonance (CMR) imaging can be useful for the assessment of function and perfusion, and the detection of scar tissue. CMR can also be useful to exclude or detect ACS, assess myocardial viability and to detect myocarditis.^[2]
• Coronary angiography provides information on the presence and severity of coronary artery disease and therefore remains the gold standard.^[2]

Risk assessment^[7]

As soon as the diagnosis of unstable angina or NSTEMI is made, and aspirin and antithrombin therapy have been offered, individual risk of future adverse cardiovascular events should be assessed using an established risk scoring system that predicts 6-month mortality. Risk is defined as:

• Low: up to 3%.
• Intermediate: above 3% and up to 6.0%.
• High: above 6.0%.

The National Institute for Health and Clinical Excellence (NICE) recommends the Global Registry of Acute Cardiac Events (GRACE) risk score.^[8] The Thrombolysis in Myocardial Infarction (TIMI) risk score is another method used to assess risk in patients with ACS.^[9]

• Recent trials have shown that, in high-risk patients, early invasive strategy (percutaneous coronary intervention (PCI) or coronary artery bypass surgery) produced a better outcome than non-invasive management.^[3][10][11]
• However, in lower-risk patients, conservative management (initial intensive medical treatment followed by non-invasive risk assessment - eg, by exercise ECG) has been found to be as effective as early invasive management.^[12]
• Factors to use when assessing risk with an established scoring system include:^[7]
  • Full clinical history, including age, previous myocardial infarction, previous PCI or coronary artery bypass graft (CABG).
  • Physical examination, including blood pressure and heart rate.
  • 12-lead resting ECG.
  • Blood tests (such as troponin I or T, creatinine, glucose and haemoglobin).
• The risk of bleeding should be assessed as well as relevant comorbidity before considering treatments and at each stage of management. Factors associated with high bleeding risk include advancing age, known bleeding complications, renal impairment and low body weight.

Management^[7]

The treatment of patients with non-ST-segment elevation ACS 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.^[1]

• Antiplatelet and anticoagulant therapy
  • Aspirin: single 300-mg loading dose to all patients, unless contra-indicated, and continue indefinitely. Consider clopidogrel monotherapy for patients with aspirin hypersensitivity.
  • Clopidogrel:
    • Offer a 300-mg loading dose to patients with a predicted 6-month mortality of more than 1.5% and no contra-indications (such as increased bleeding risk).
    • Offer a 300-mg loading dose to all patients with no contra-indications who may undergo PCI within 24 hours of admission.
    • Continue standard dose for 12 months.
    • Consider stopping clopidogrel 5 days before CABG in patients with low risk. For patients at intermediate or higher risk, whether to continue clopidogrel before CABG depends on the balance of ischaemic and bleeding risk.
  • Prasugrel in combination with aspirin is recommended as an option for preventing atherothrombotic events in people with ACS having percutaneous coronary intervention, only when:^[13]
    • immediate primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction is necessary; or
    • stent thrombosis has occurred during clopidogrel treatment; or
    • the patient has diabetes mellitus.
  • Ticagrelor in combination with low-dose aspirin is recommended for up to 12 months as a treatment option in adults with ACS with:^[14]
    • STEMI that cardiologists intend to treat with primary percutaneous coronary intervention (PCI); or
    • NSTEMI; or
    • admitted to hospital with unstable angina.
  • Glycoprotein IIb/IIIa inhibitors:
    • Consider eptifibatide or tirofiban for patients at intermediate or higher risk if angiography is scheduled within 96 hours of admission.
    • Consider abciximab as an adjunct to PCI for patients at intermediate or higher risk who are not already receiving a glycoprotein inhibitor (GPI).
  • Antithrombin therapy: anticoagulants are used in the treatment of NSTE-ACS to inhibit thrombin generation and/or activity, thereby reducing thrombus-related events.^[2]
    • Offer fondaparinux to patients without a high bleeding risk unless angiography is planned within 24 hours of admission. Offer unfractionated heparin as an alternative to fondaparinux if angiography is likely within 24 hours of admission.
    • Carefully consider the choice and dose of antithrombin in patients with a high bleeding risk.
    • Consider unfractionated heparin, with dose adjusted to clotting function, for patients with creatinine above 265 μmol/L.
    • Offer systemic unfractionated heparin (50-100 units/kg) in the cardiac catheter laboratory to patients on fondaparinux who are undergoing PCI.
    • As an alternative to the combination of a heparin plus a GPI, consider bivalirudin for patients who are at intermediate or higher risk, and are not already receiving a GPI or fondaparinux, and are scheduled for angiography within 24 hours of admission.
    • As an alternative to the combination of a heparin plus a GPI, consider bivalirudin for patients undergoing PCI who are at intermediate or higher risk and are not already on a GPI or fondaparinux.
• Revascularisation:
• Patients with NSTE-ACS should be assessed for risk (using GRACE scoring system, as above) of cardiovascular event. If they are medium to high risk they should be offered early in-hospital coronary angiography, possibly with GPIIb/IIIa inhibitor.^[15] 
• If the patient is low-risk but symptoms are recurring, they should also be offered coronary angiogeraphy.
• The proportion of patients with NSTE-ACS undergoing CABG surgery during initial hospitalisation is about 10%. The benefit from bypass surgery is greatest when patients can be operated on after several days of medical stabilisation, depending on the individual risk.^[2]
• Other treatments:
  • 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 (eg, diltiazem, verapamil) are used for patients who cannot tolerate a beta-blocker, or are used in addition to a beta-blocker. Verapamil should not be combined with a beta-blocker.
  • Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and should be started when the patient is an inpatient unless contra-indicated.
  • Hyperglycaemia:^[6]
    • Hyperglycaemia in patients admitted to hospital for an ACS should be managed by keeping blood glucose levels below 11.0 mmol/L while avoiding hypoglycaemia. A dose-adjusted insulin infusion with regular monitoring of blood glucose levels should be considered.
    • All patients with hyperglycaemia after ACS and without known diabetes should be tested for HbA1c levels before discharge and fasting blood glucose levels no earlier than 4 days after the onset of ACS.
  • 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.^[11] If a patient was stabilised with medical treatment then it is likely they will undergo treadmill exercise testing.

Further management

• To detect and quantify inducible ischaemia, consider ischaemia testing before discharge for patients whose condition has been managed conservatively and who have not had coronary angiography.
• Assess left ventricular function in all patients who have had a myocardial infarction and consider assessing left ventricular function in all patients with unstable angina.
• Cardiac rehabilitation: rehabilitation and discharge planning.
• Secondary prevention: management of cardiovascular risk factors with lifestyle changes and drug therapy as indicated.

Complications

• 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 nonsustained ventricular tachycardia
• Atrioventricular nodal blockade: usually transient in setting of reversible ischaemia (treatment is guided by location of block and haemodynamic stability).

Prognosis

People with non-ST-segment elevation ACS have a high incidence of recurrent myocardial ischaemia, a similar long-term outcome to those with STEMI, and a worse outcome than for people with unstable angina.^[7]

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. Factors associated with a poorer prognosis include:^[7]

• Advancing age.
• Presence and severity of ECG changes of ischaemia.
• Magnitude of rise in biomarkers of myocardial injury (eg, serum troponin).
• Left ventricular dysfunction, cardiogenic shock.
• Increased heart rate, arrhythmias (ventricular fibrillation, atrial fibrillation).
• Renal impairment.
• Diabetes mellitus.
• Anaemia.
• Cerebrovascular disease, peripheral vascular disease.

Any delay in arranging angiography for high-risk patients is associated with increased mortality and adverse outcomes.^[16]

Prevention

Primary cardiovascular disease prevention and cardiovascular risk assessment:

• 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 (eg, left ventricular hypertrophy, aortic stenosis).