UNSTABLE ANGINA

Figure 18.68 The spectrum of acute coronary syndromes. The relation between ECG changes, biochemical markers of damage and the extent of myocardial necrosis. (CK = creatine kinase) Unstable angina is a clinical syndrome that is characterised by new-onset or rapidly worsening angina (crescendo angina), angina on minimal exertion or angina at rest. The condition shares common pathophysiological mechanisms with acute myocardial infarction (Fig. 18.59, p. 579) and the term 'acute coronary syndrome' is used to describe these disorders collectively. These entities comprise a spectrum of disease that encompasses ischaemia with no myocardial damage, ischaemia with minimal myocardial damage, partial thickness (non-Q wave) myocardial infarction, and full thickness (Q wave) myocardial infarction (Fig. 18.68). Figure 18.69 Right coronary angiogram in a patient with an acute coronary syndrome demonstrating a thrombus filling defect (arrow). page 589 page 590 An acute coronary syndrome may present as a new phenomenon or against a background of chronic stable angina. The culprit lesion is usually a complex ulcerated or fissured atheromatous plaque with adherent platelet-rich thrombus and local coronary artery spasm (Fig. 18.69). It is important to appreciate that this is a dynamic process whereby the degree of obstruction may either increase by accretion and changes in plaque morphology, sometimes leading to complete occlusion of the vessel, or regress, sometimes only temporarily, due to the effects of platelet disaggregation and endogenous fibrinolysis. Diagnosis and risk stratification The assessment of acute chest pain depends heavily on an analysis of the character of the pain and its associated features, evaluation of the ECG, and serial measurements of biochemical markers of cardiac damage, such as troponin I and T. A 12-lead ECG is mandatory and is the most useful method of initial triage (Fig. 18.18, p. 538). Evolving transmural infarction is characterised by persistent ST elevation, new Q waves or new left bundle branch block, and is discussed in the next section. In patients with unstable angina or partial thickness (non-Q wave or non-ST elevation) myocardial infarction, the ECG may show ST/T wave changes including ST depression, transient ST elevation and T-wave inversion; the T-wave changes are sometimes prolonged. Approximately 12% of patients with well-characterised unstable angina or non-ST segment elevation myocardial infarction progress to acute infarction or death, and almost one-third will suffer a recurrence of severe ischaemic pain, within 6 months of the index event. The risk markers that are indicative of an adverse prognosis include recurrent ischaemia, extensive ECG changes at rest or during pain, the release of biochemical markers (creatine kinase or troponin, p. 593), arrhythmias and haemodynamic complications (e.g. hypotension, mitral regurgitation) during episodes of ischaemia; those who experience unstable angina following acute myocardial infarction are also at increased risk. Risk stratification is important because it guides the use of more complex pharmacological and interventional treatment (Box 18.65 and Fig. 18.18). Management 18.65 UNSTABLE ANGINA: RISK STRATIFICATION   High risk Low risk Clinical Post-infarct angina Recurrent pain at rest Heart failure No history of MI Rapid resolution of symptoms ECG Arrhythmia ST depression Transient ST elevation Persistent deep T-wave inversion Minor or no ECG changes Biochemistry Troponin T > 0.1 μg/l Troponin T < 0.1 μg/l N.B. There is a 5- to 10-fold difference in risk between the lowest and highest risk groups. 18.66 ORAL ANTIPLATELET AGENTS IN UNSTABLE ANGINA 'Aspirin alone (75-325 mg/day) reduces the risk of death and myocardial infarction in unstable angina (NNTB = 20). The combination of clopidogrel (75 mg daily) and aspirin is superior to aspirin alone (NNTB for death, MI and stroke = 45).' Antithrombotic Trialists Collaboration. BMJ 2002; 324:71-86. Clopidogrel in Unstable Angina to prevent Recurrent Events (CURE) trial investigators. N Engl J Med 2001; 345:494-502.

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18.67 LOW MOLECULAR WEIGHT HEPARIN IN UNSTABLE ANGINA

'Treating patients with unstable angina with aspirin plus low molecular weight heparin is more effective than aspirin alone in reducing the combined endpoint of death, myocardial infarction, refractory angina and urgent need for revascularisation.'

Antman EM, et al. for the TIMI IIB (Thrombolysis in Myocardial Infarction) and ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events) Investigators. TIMI IIB-ESSENCE meta-analysis. Circulation 1999; 100:1602-1608. Eikelboom JW, et al. Lancet 2000; 355:1936-1942.

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18.68 INTRAVENOUS GLYCOPROTEIN IIb/IIIa INHIBITORS IN ACUTE CORONARY SYNDROMES

'In patients with acute coronary syndromes, antiplatelet treatment with i.v. glycoprotein IIb/IIIa inhibitors reduced the combined endpoint of death or myocardial infarction. Most benefit was seen in the context of percutaneous coronary intervention and there was no convincing evidence of benefit in patients who were treated without revascularisation. (NNTB (death or MI) = 50; NNTB (death, MI or revascularisation) = 33).'

Kong DF, et al. Circulation 1998; 2829-2835. Bertrand ME, et al. Eur Heart J 2000; 21:1406-1432.

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Patients should be admitted urgently to hospital because there is a significant risk of death or acute myocardial infarction during the unstable phase, and appropriate medical therapy can reduce the incidence of adverse events by at least 60%.

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18.69 ANGINA IN OLD AGE

Incidence: coronary artery disease increases and affects women almost as often as men. Comorbid conditions: anaemia and thyroid disease are common and may worsen angina. Calcific aortic stenosis: common and should be sought in all old people with angina. Atypical presentations: when myocardial ischaemia occurs, age-related changes in myocardial compliance and diastolic relaxation can cause the presentation to be with symptoms of heart failure such as breathlessness, rather than with chest discomfort. Angioplasty and coronary artery bypass surgery: provide symptomatic relief although with an increased procedure-related morbidity and mortality. Outcome is determined by the number of diseased vessels, severity of cardiac dysfunction and the number of concomitant diseases, as much as age itself.

Figure 18.70 A guide to the investigation and treatment of unstable angina and non-ST segment elevation myocardial infarction (NSTEMI). See Figure 18.18 on page 538, Box 18.65 and text for identification of high- and low-risk patients.

The initial treatment should include bed rest, antiplatelet therapy (aspirin 300 mg followed by 75-325 mg daily long-term and clopidogrel 300 mg followed by 75 mg daily for 12 months, Box 18.66), anticoagulant therapy (e.g. unfractionated or fractionated heparin) and a β-blocker (e.g. atenolol 50-100 mg daily or metoprolol 50-100 mg 12-hourly). A dihydropyridine calcium antagonist (e.g. nifedipine or amlodipine) can be added to the β-blocker, but may cause an unwanted tachycardia if used alone; verapamil or diltiazem is therefore the calcium antagonist of choice if a β-blocker is contraindicated. An intravenous infusion of unfractionated heparin (with dose adjusted according to the activated partial thromboplastin time) or weight-adjusted subcutaneous low molecular weight heparin (e.g. enoxaparin 1 mg/kg 12-hourly) should be given (Box 18.67). If pain persists or recurs, infusions of intravenous nitrates (e.g. GTN 0.6-1.2 mg/hr or isosorbide dinitrate 1-2 mg/hr) or buccal nitrates may help, but such patients should also be considered for early revascularisation. Refractory cases or those with haemodynamic compromise should be considered for a glycoprotein IIb/IIIa receptor antagonist (e.g. abciximab, tirofiban or eptifibatide), intra-aortic balloon pump or emergency coronary angiography (Box 18.68).

Most low-risk patients stabilise with aspirin, clopidogrel, heparin and anti-anginal therapy, and can be gradually mobilised. If there are no contraindications, exercise testing may be performed prior to or shortly following discharge. Coronary angiography should be considered with a view to revascularisation in all patients at moderate or high risk, including those who fail to settle on medical therapy, those with extensive ECG changes, those with an elevated plasma troponin and those with severe pre-existing stable angina. This often reveals disease that is amenable to PCI (Fig. 18.70); however, if the lesions are not suitable for PCI the patient should be considered for urgent CABG.