In some cases, this investigation will be repeated at half-hourly intervals, allowing early detection of changes of myocardial infarction and resolution of acute ischaemic changes.

Continuous 12-lead ST segment monitoring, allowing detection of transient changes in these can be used if available (Bassand et al., 2007), but otherwise standard cardiac monitoring should be commenced.

Patients presenting with a history suggestive of unstable angina should not be discharged home on the basis of a normal ECG, unless their history and investigation results have been reviewed by a senior member of medical staff. Several studies have noted alarmingly high numbers of patients with chest pain discharged from Emergency Departments who were subsequently found to have unstable angina or myocardial infarction (Bassand et al., 2007). However, diagnosis of unstable angina does not depend on the patient having ECG changes.

Venous blood should be sent for urea and electrolytes, liver function tests, troponin, full blood count, glucose and C-reactive protein. The patient’s potassium should be normalised and creatinine level will be used in risk stratification. Although creatinine is utilised rarely as a risk tool, it has been reported that patients with elevated creatinine will have a higher risk stratification score (Granger et al., 2003).

Anaemia reduces the capacity of the blood to carry oxygen and may exacerbate the symptoms of unstable angina. Elevated blood glucose should be controlled with insulin if necessary. Elevated C-reactive protein is known to be predictive of a higher risk of death or myocardial infarction in the six months after the presenting event (Heeschen et al., 2000). An arterial blood gas sample may be taken if the patient is breathless or has a low oxygen saturation on oximetry. Oxygen may be administered even with normal saturation. A portable chest X-ray should be requested to exclude other pathology. Echocardiography should be carried out to assess left ventricular function and to detect structural or wall motion abnormalities.

Treatment Strategies

The management of unstable angina is aimed at reducing oxygen demand and prevention of further thrombus formation or proliferation. Despite the presence of clot in the coronary artery, no benefit has been demonstrated from the use of fibrinolytics in unstable angina.

The five main categories of the immediate management of unstable angina are:

• rest and analgesia
  
• anti-ischaemic therapy
  
• anti-platelet therapy
  
• anticoagulants
  
• plaque stabilisation.

Rest and Analgesia

As the symptoms of unstable angina are caused by a reduced oxygen supply to the myocardium, there is a certain logic in limiting the amount of oxygen consumed in other tissues by preventing the patient from exercising. On a practical note, having the patient confined to bed allows them to be closely observed and their vital signs, including their heart rhythm, to be monitored. All patients with acute coronary syndromes should be treated in a high dependency care area, with resuscitation equipment and qualified staff trained in its use should resuscitation to be required.

Patients with unstable angina will usually require analgesia, for example opiates such as morphine or diamorphine. These should be administered intravenously. An anti-emetic may also be administered with these.

Anti-Ischaemic Therapy

These treatments are targeted at reducing the oxygen consumption of the myocardium by reducing its work.

Nitrates, such as glyceryl trinitrate (GTN), may be given by sublingual spray, by buccally absorbed tablets or by continuous intravenous infusion. These reduce cardiac work by reducing preload and left ventricular end diastolic pressure. They also cause systemic vasodilation and may improve blood flow in the coronary arteries by dilating these. Patients on nitrate infusions should have their blood pressure closely monitored as this vasodilation can cause hypotension.

Beta-blockers prevent noradrenaline binding to beta adrenoceptors in sympathetic neurons and reduce oxygen consumption, in the main by slowing the heart rate. They may worsen asthma, heart failure and diabetes, and should be used cautiously where patients have any of these. Beta-blockers are contraindicated in patients with known bradycardia or heart block.

Calcium channel blockers reduce oxygen consumption in a similar manner to nitrates, by causing vasodilation. Some will also cause a slight reduction in heart rate. These drugs are useful where symptoms are exacerbated by coronary artery spasm (Bassand et al., 2007). Rate-slowing calcium channel blockers such as diltiazem or verapamil vasodilate and reduce the heart rate, and can be effective therapies in patients who have contraindications to beta-blockers. They should not be used in the presence of bradycardias, heart block or heart failure.

Anti-Platelet Therapy

Thrombus is a matrix formed by activated platelets and fibrin strands. The aim of anti-platelet and anticoagulant therapy is to prevent extension and reduce the size of existing thrombus, as well as preventing new thrombus from being formed.

Platelets are activated by a number of pathways, which means that simply blocking one pathway will not prevent activation. Anti-platelet drugs used in unstable angina therefore target both platelet activation and the receptors that bind fibrinogen to link adjacent platelets, the glycoprotein IIb/IIIa receptors (Table 5.1).

Table 5.1 Summary of actions of anticoagulant and anti-platelet drugs

Platelet activation is mediated by a balance between two compounds. Thromboxane α_2, which promotes aggregation, and prostacyclin, which inhibits aggregation. Low-dose aspirin prevents synthesis of thromboxane α₂; at higher doses prostacyclin is also inhibited (Rang et al., 2001). A number of large trials have shown the benefit of low-dose aspirin in ACS (Collins et al., 1997). Patients with unstable angina should have aspirin 300 mg, either chewed or crushed, as soon as possible, and 75–150 mg daily thereafter (Patrono et al., 2004). Buccal absorption of the crushed or chewed aspirin allows rapid anti-platelet activity. The main contraindications to aspirin are allergy and gastrointestinal bleeding.

The glycoprotein IIb/IIIa receptors that allow platelets to bind to each other are activated by ADP. Clopidogrel (Plavix), is one example, which inhibits this ADP-dependent activation, reducing the ability of platelets to clump together. Patients with unstable angina should have clopidogrel 300 mg orally as soon as possible and 75 mg daily, for up to 12 months (Bassand et al., 2007); higher loading doses of 600 mg are used it the patient is going for urgent angiography. The main contraindication to clopidogrel is bleeding. Caution is needed with non-steroidal anti-inflammatory drugs as their metabolism may be slowed.

Anticoagulant Therapy

Heparin and the synthetic pentasaccharide fondaparinux (Arixtra) inhibit the binding of factor Xa in the blood, preventing prothrombin being converted to thrombin in the early part of the coagulation cascade, which results in the formation of fibrin. Platelets produce factor Xa, which is protected from the actions of unfractionated heparin, and platelet factor 4, which neutralises unfractionated heparin. Low molecular weight heparin is not modified by this platelet activity (Rang et al., 2001). In addition, low molecular weight heparin given subcutaneously does not need to be closely monitored by blood sampling. Patients with unstable angina should commence anticoagulation with low molecular weight heparin as soon as possible. Bivalirudan (Angiomax), which acts as a direct thrombin inhibitor may also be added.

Plaque Stabilisation

Given that unstable angina is a disease of unstable plaque in the coronary arteries, there has been interest in recent years in ways to stabilise this. Statins, (HMG co-enzyme A reductase inhibitors) are mainstay drugs in primary and secondary prevention of coronary heart disease, acting to reduce low-density lipoprotein cholesterol, and have been demonstrated to reduce the incidence of acute cardiovascular events. The finding at angiography that despite lipid lowering with statins, in most cases established plaques do not shrink in size, together with animal models which suggest that statins alter the components of plaque, has led to the view that these drugs act, in part, by reducing the propensity of plaque to rupture or erode (Braganza and Bennett, 2001); there has been exception of late with some evidence suggesting that atorvastatin does actually cause plaque regression (Yonemura et al., 2005). Whether this is by anti-inflammatory action or changing the proportions of the constituents of plaque is unclear. Patients with unstable angina should receive lipid reduction treatment with statins as early as possible in their admission.

Angiotensin-converting enzyme inhibitors such as ramipril or enalapril are also thought to have an anti-atherosclerotic effect and have been shown to reduce adverse events in patients with stable coronary heart disease. There has been a recent recommendation that these drugs should be prescribed to patients with unstable disease, including unstable angina (Bassand et al., 2007; HOPE, 2000).

Revascularisation

Patients with no ECG changes during pain who are troponin-negative need consideration of all causes of chest pain, including coronary disease. Non-invasive assessment for low-risk patients with stress testing with plain exercise, nuclear cardiology or stress echocardiography can be used to risk stratify low-risk patients. High-risk patients or patients who have positive non-invasive assessment should have angiography with a view to revascularisation prior to discharge (see Chapter 6).

Summary

Unstable angina is part of the spectrum of acute coronary syndromes and is a clinical syndrome caused by plaque rupture and erosion with thrombus formation in the coronary arteries, or by increasing narrowing of the stenosis. It carries significant mortality at both at 30 days and at six months after the acute event. Diagnosis is made on a patient history of prolonged chest pain, new chest pain on minimal exercise, crescendo pain or pain following previous myocardial infarction. The ECG will have no new signs of myocardial infarction and the patient’s troponin level will be normal.

Patients’ risk profiles should be evaluated, and all causes of chest pain should be considered in patients with normal ECGs and negative troponins. Low-risk patients can be considered for non-invasive assessment prior to discharge. High-risk patients or patients with positive non-invasive tests should have inpatient angiography to elucidate the right revascularisation strategy.

References

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