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A Textbook of Clinical Pharmacology and Therapeutics

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198 ISCHAEMIC HEART DISEASE<br />

MINIMAL/INFREQUENT<br />

SYMPTOMS<br />

Sublingual GTN as<br />

required (tablets or<br />

preferably spray<br />

Aspirin 75 mg once daily<br />

Statin therapy<br />

Figure 29.2: Drug therapy <strong>of</strong> stable angina.<br />

lesions whose symptoms are not adequately controlled by<br />

medical therapy alone. Several antiplatelet drugs are given at<br />

the time <strong>of</strong> PCI, including oral aspirin <strong>and</strong> clopidogrel, <strong>and</strong> a<br />

glycoprotein IIb/IIIa inhibitor given intravenously such as<br />

abciximab, eptifibatide or tir<strong>of</strong>iban (Chapter 30). Aspirin<br />

is usually continued indefinitely <strong>and</strong> clopidogrel is usually<br />

continued for at least one month following the procedure.<br />

MANAGEMENT OF UNSTABLE CORONARY<br />

DISEASE<br />

ACUTE CORONARY SYNDROME<br />

SIGNIFICANT/REGULAR<br />

SYMPTOMS<br />

Beta blocker<br />

(e.g. atenolol)<br />

Diltiazem or verapamil if intolerant<br />

to beta blocker<br />

Dihydropyridine calcium<br />

antagonist (e.g. amlodipine<br />

or nifedipine) or long acting nitrate<br />

(e.g. isosorbide mononitrate)<br />

if intolerant <strong>of</strong> above<br />

Consider nicor<strong>and</strong>il if above<br />

incompletely effective, poorly<br />

tolerated or contraindicated<br />

Acute coronary syndrome (ACS) is a blanket term used to<br />

describe the consequences <strong>of</strong> coronary artery occlusion,<br />

whether transient or permanent, partial or complete. These<br />

different patterns <strong>of</strong> coronary occlusion give rise to the<br />

different types <strong>of</strong> ACS, namely unstable angina (where no<br />

detectable myocardial necrosis is present), non-ST-segmentelevation<br />

myocardial infarction (NSTEMI) <strong>and</strong> ST-segmentelevation<br />

myocardial infarction (STEMI, usually larger in<br />

extent <strong>and</strong> fuller in thickness <strong>of</strong> myocardial wall affected than<br />

NSTEMI). A flow chart for management <strong>of</strong> ACS is given in<br />

Figure 29.3. Unstable angina <strong>and</strong> NSTEMI are a continuum <strong>of</strong><br />

disease, <strong>and</strong> usually only distinguishable by the presence <strong>of</strong><br />

a positive serum troponin test in NSTEMI (troponin now being<br />

the gold st<strong>and</strong>ard serum marker <strong>of</strong> myocardial damage); their<br />

management is similar <strong>and</strong> discussed further here. Management<br />

<strong>of</strong> STEMI is discussed separately below. All patients with ACS<br />

must stop smoking. This is more urgent than in other patients<br />

with coronary artery disease, because <strong>of</strong> the acute pro-thrombotic<br />

effect <strong>of</strong> smoking.<br />

Patients with ACS require urgent antiplatelet therapy, in the<br />

form <strong>of</strong> aspirin <strong>and</strong> clopidogrel (Chapter 30), plus antithrombotic<br />

therapy with heparin (nowadays most <strong>of</strong>ten lowmolecular-weight<br />

heparin administered subcutaneously; see<br />

Chapter 30). Data from the CURE trial suggest that combined<br />

aspirin <strong>and</strong> clopidogrel treatment is better than aspirin alone,<br />

<strong>and</strong> that this combination should be continued for several<br />

months, <strong>and</strong> preferably for up to a year, following which aspirin<br />

alone should be continued. This antiplatelet/antithrombotic<br />

regime approximately halves the likelihood <strong>of</strong> myocardial<br />

infarction, <strong>and</strong> is the most effective known treatment for improving<br />

outcome in pre-infarction syndromes. By contrast, GTN,<br />

while very effective in relieving pain associated with unstable<br />

angina, does not improve outcome. It is usually given as a constant-rate<br />

intravenous infusion for this indication. A β-blocker is<br />

prescribed if not contraindicated. If β-blockers are contraindicated,<br />

a long-acting Ca 2� -antagonist is a useful alternative.<br />

Diltiazem is <strong>of</strong>ten used as it does not cause reflex tachycardia<br />

<strong>and</strong> is less negatively inotropic than verapamil. β-Blockers <strong>and</strong><br />

Ca 2� -antagonists are <strong>of</strong>ten prescribed together, but there is disappointingly<br />

little evidence that their effects are synergistic or<br />

even additive. Moreover, there is a theoretical risk <strong>of</strong> severe<br />

bradycardia or <strong>of</strong> precipitation <strong>of</strong> heart failure if β-blockers<br />

are co-administered with these negatively chronotropic <strong>and</strong><br />

inotropic drugs, especially so for verapamil; where concomitant<br />

β-blockade <strong>and</strong> calcium-channel blockade is desired, it<br />

is probably safest to use a dihydropyridine calcium-channel<br />

blocker (e.g. nifedipine or amlodipine) rather than verapamil<br />

or diltiazem. Nicor<strong>and</strong>il is now <strong>of</strong>ten added as well, but again<br />

there is not much evidence <strong>of</strong> added benefit. Coronary angiography<br />

is indicated in patients who are potentially suitable for PCI<br />

or CABG, <strong>and</strong> should be considered as an emergency in patients<br />

who fail to settle on medical therapy.<br />

ST-ELEVATION-MYOCARDIAL INFARCTION<br />

(STEMI)<br />

ACUTE MANAGEMENT<br />

Oxygen<br />

This is given in the highest concentration available (unless<br />

there is coincident pulmonary disease with carbon dioxide<br />

retention) delivered by face mask (FiO2 approximately 60%) or<br />

by nasal prongs if a face mask is not tolerated.<br />

Pain relief<br />

This usually requires an intravenous opiate (morphine or<br />

diamorphine; see Chapter 25) <strong>and</strong> concurrent treatment with<br />

an anti-emetic (e.g. promethazine or metoclopramide; see<br />

Chapter 34).

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