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Acute Coronary Syndromes: Unstable Angina And Non-ST Segment Elevation Myocardial Infarction


Acute Coronary Syndromes: Unstable Angina And Non-ST Segment Elevation Myocardial Infarction
Stable angina is a chronic condition that occurs on a relatively predictable basis on exertion when cardiac ischaemia develops due to the inability of a narrowed coronary artery to meet an increased cardiac oxygen demand. Conversely, the acute coronary syndromes (ACS), including in ascending order of severity, unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI), represent a spectrum of dangerous conditions in which myocardial ischaemia results from  a sudden  decrease in the  flow of  blood through a coronary vessel. This decrease is almost always initiated by the rupture of an atherosclerotic plaque, resulting in the formation of an intracoronary thrombus that diminishes or abolishes the flow of blood.

When a patient presents with suspected ACS, serial ECGs are immediately carried out. The hallmark of STEMI is sustained elevation of the ST segments of the ECG (Figure 42, upper left). This indicates that a large area of the myocardium, probably involving the full thickness of a ventricular wall, has developed a lesion as a result of prolonged ischaemia. Myocardial damage releases intracellular proteins, such as troponins T and I into the blood. These serve as important markers of myocardial injury and as a prognostic tool. STEMI is confirmed when elevated levels of these markers are found in addition to the requisite ECG changes. STEMI typically occurs when a thrombus has completely occluded a coronary artery for a significant period of time, and usually causes more severe symptoms than do unstable angina or NSTEMI. Incomplete or temporary coronary occlusion, or the existence of collateral coronary arteries that can maintain some supply of blood to the affected region, may result in a smaller degree of myocardial infarction (MI) and necrosis. This may not result in ST segment elevation, but does cause increased levels of cardiac markers of damage in the plasma. Patients with ACS who are found to have elevated levels of these markers, but who do not exhibit  ST segment  elevation, are deemed to have  suffered and
Acute Coronary Syndromes: Unstable Angina And Non-ST Segment Elevation Myocardial Infarction, NSTEMI, Pathophysiology of UA/NSTEMI, Drug treatment of UA/NSTEMI, Antiplatelet therapy, Antithrombin therapy Low molecular weight heparins (LMWHs), Glycoprotein IIb/IIIa antagonists,

NSTEMI.
Patients who demonstrate symptoms associated with ACS, but who have neither ST segment elevation nor raised levels of troponins, are deemed to have unstable angina. In this case, it is likely that the coronary obstruction has been of limited extent and/or duration (<20 min), and is thus sufficient to cause ischaemia but not detectable injury. Both NSTEMIs and UA may be associated with ECG changes other than ST elevation, for example ST segment depression and T-wave inversion.
Both NSTEMI and STEMI are grouped together as acute MIs, but are managed differently in the acute phase, in that reperfusion therapies, either pharmacological (thrombolysis), or preferably percutaneous coronary intervention is used to treat STEMI but not NSTEMI (see Chapters 43 and 45). Symptoms of UA/NSTEMI resemble those of stable angina, but they are frequently more painful, intense and persistent, often lasting at least 30 min. Pain is frequently unrelieved by glyceryl trinitrate. Typical presentations include:
·   Crescendo angina, where attacks are progressively more severe, prolonged and frequent
·   Angina of recent onset brought on by minimal exertion
·   Angina at rest/with minimal exertion or during sleep
·   Post-MI angina (ischaemic pain 24 h to 2 weeks after MI).

Pathophysiology of UA/NSTEMI
Studies have shown that episodes of unstable angina are preceded by a fall in coronary blood flow, thought to result from the periodic development of coronary thrombosis and vasoconstriction, which are triggered by coronary artery disease (Figure 42).
Thrombosis is promoted by the endothelial damage and turbulent blood flow associated with atherosclerotic plaques. Compared with the lesions of stable angina, plaques found in patients with ACS tend to have a thinner fibrous cap and a larger lipid core, and are generally more widespread and severe. These stenoses are often eccentric – the plaque does not surround the entire circumference of the artery. Such lesions are especially vulnerable to being ruptured by haemodynamic stress. This exposes the plaque interior, which powerfully stimulates platelet aggregation and thrombosis. The thrombus propagates out into the coronary lumen, occluding the artery. Rupture may also cause haemorrhage into the lesion itself, expanding it out into the lumen and worsening stenosis.
These events may be exacerbated by impaired coronary vasodilatation, and vasospasm due to plaque-associated endothelial damage, which reduces the local release of endothelium-dependent relaxing factors, such as nitric oxide. Platelet aggregation and thrombosis also cause the local generation of vasoconstrictors such as thromboxane A2 and serotonin.

Risk stratification
The occurrence of UA and NSTEMI indicates that a patient has a high risk of undergoing subsequent episodes of coronary thrombosis which may cause more significant cardiac damage or death. In the USA, for example, 4% of the 1.3 million people who enter hospital with UA/NSTEMI die within 30 days, and 8% experience (re)infarction. Although NSTEMI is by definition a more serious ‘event’ than UA, in that myocardial necrosis has occurred, these are both heterogeneous conditions, and the risk of (re)infarction is higher in some patients with UA than in some with NSTEMI. Risk assessment is therefore of paramount importance.
Risk is scored on the basis of a number of factors, including frequency and severity of angina, elevated markers of cardiac necrosis, ECG changes (ST segment depression and/or T-wave inversion) and prior angiographic evidence of atherosclerotic plaque.

Management
UA/NSTEMI is a medical emergency. Patients are started on the ‘ACS protocol’, which consists of aggressive pharmacological therapy. This renders the acute coronary lesion less dangerous, minimizing residual ischaemia and reducing the likelihood of future coronary events. Urgent revascularization is considered for patients with high-risk and/or very significant coronary artery disease, or if drug treatment fails to control symptoms (see Chapter 43).

Drug treatment of UA/NSTEMI (see also Chapter 8 for drug mechanisms)
Antiplatelet therapy All patients with UA/NSTEMI are immediately treated with 300 mg aspirin. This is then reduced to a smaller dose of 75 mg/day, which is continued for life. Aspirin is effective in treating ACS because it suppresses platelet aggregation, a key initial step in thrombosis. Clinical trials have shown that it reduces mortality or infarction by more than 50%.
The thienopyridine clopidogrel, which inhibits ADP-stimulated platelet aggregation, was shown in the 2000 CURE trial to reduce cardiovascular morbidity and mortality by 20% in patients with UA/NSTEMI. Patients should be given 300 mg clopidogrel initially and then receive 75 mg/day for 12 months.

Antithrombin therapy Low molecular weight heparins (LMWHs) (e.g. dalteparin and similar drugs such as fondaparinux) which inhibit the coagulation cascade mainly at factor X and thrombin, are given to all patients with UA/NSTEMI. LMWH is given subcutaneously while patients are hospitalized, but not routinely thereafter.

Glycoprotein IIb/IIIa antagonists (e.g. tirofiban) are the most powerful of the antiplatelet drugs. These drugs are of proven benefit in UA/NSTEMI patients who receive percutaneous coronary intervention (PCI), a type of revascularization procedure in which plaque-stenosed coronary arteries are widened using a balloon catheter (see Chapter 43). PCI usually involves placing a medicated stent (a mesh tube) in the affected coronary to keep it open, and the glycoprotein IIb/IIIa antagonists reduce the tendency of stents to cause thrombosis.

Other drugs β-Blockers have been shown to reduce cardiovascular morbidity and mortality in patients with UA/NSTEMI, and should be given unless contraindicated (e.g. in moderate and severe asthma). Nitrates can be given, especially on a temporary basis, to relieve pain and to control symptoms of heart failure, but do not appear to reduce mortality. Ca2+-channel blockers should not be used to treat UA/NSTEMI, although they may be continued if the patient is already receiving them for chronic stable angina. On the other hand, there is increasing evidence that statins and angiotensin-converting enzyme inhibitors improve survival in/NSTEMI.