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
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:
·
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).
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.
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.