Clinical Pharmacology and Therapeutics

198 ISCHAEMIC HEART DISEASE
MINIMAL/INFREQUENT
SYMPTOMS
Sublingual GTN as
required (tablets or
preferably spray
Aspirin 75 mg once daily
Statin therapy
Figure 29.2: Drug therapy of stable angina.
lesions whose symptoms are not adequately controlled by
medical therapy alone. Several antiplatelet drugs are given at
the time of PCI, including oral aspirin and clopidogrel, and a
glycoprotein IIb/IIIa inhibitor given intravenously such as
abciximab, eptifibatide or tirofiban (Chapter 30). Aspirin
is usually continued indefinitely and clopidogrel is usually
continued for at least one month following the procedure.
MANAGEMENT OF UNSTABLE CORONARY
DISEASE
ACUTE CORONARY SYNDROME
SIGNIFICANT/REGULAR
SYMPTOMS
Beta blocker
(e.g. atenolol)
Diltiazem or verapamil if intolerant
to beta blocker
Dihydropyridine calcium
antagonist (e.g. amlodipine
or nifedipine) or long acting nitrate
(e.g. isosorbide mononitrate)
if intolerant of above
Consider nicorandil if above
incompletely effective, poorly
tolerated or contraindicated
Acute coronary syndrome (ACS) is a blanket term used to
describe the consequences of coronary artery occlusion,
whether transient or permanent, partial or complete. These
different patterns of coronary occlusion give rise to the
different types of ACS, namely unstable angina (where no
detectable myocardial necrosis is present), non-ST-segmentelevation
myocardial infarction (NSTEMI) and ST-segmentelevation
myocardial infarction (STEMI, usually larger in
extent and fuller in thickness of myocardial wall affected than
NSTEMI). A flow chart for management of ACS is given in
Figure 29.3. Unstable angina and NSTEMI are a continuum of
disease, and usually only distinguishable by the presence of
a positive serum troponin test in NSTEMI (troponin now being
the gold standard serum marker of myocardial damage); their
management is similar and discussed further here. Management
of STEMI is discussed separately below. All patients with ACS
must stop smoking. This is more urgent than in other patients
with coronary artery disease, because of the acute pro-thrombotic
effect of smoking.
Patients with ACS require urgent antiplatelet therapy, in the
form of aspirin and clopidogrel (Chapter 30), plus antithrombotic
therapy with heparin (nowadays most often lowmolecular-weight
heparin administered subcutaneously; see
Chapter 30). Data from the CURE trial suggest that combined
aspirin and clopidogrel treatment is better than aspirin alone,
and that this combination should be continued for several
months, and preferably for up to a year, following which aspirin
alone should be continued. This antiplatelet/antithrombotic
regime approximately halves the likelihood of myocardial
infarction, and is the most effective known treatment for improving
outcome in pre-infarction syndromes. By contrast, GTN,
while very effective in relieving pain associated with unstable
angina, does not improve outcome. It is usually given as a constant-rate
intravenous infusion for this indication. A β-blocker is
prescribed if not contraindicated. If β-blockers are contraindicated,
a long-acting Ca 2 -antagonist is a useful alternative.
Diltiazem is often used as it does not cause reflex tachycardia
and is less negatively inotropic than verapamil. β-Blockers and
Ca 2 -antagonists are often prescribed together, but there is disappointingly
little evidence that their effects are synergistic or
even additive. Moreover, there is a theoretical risk of severe
bradycardia or of precipitation of heart failure if β-blockers
are co-administered with these negatively chronotropic and
inotropic drugs, especially so for verapamil; where concomitant
β-blockade and calcium-channel blockade is desired, it
is probably safest to use a dihydropyridine calcium-channel
blocker (e.g. nifedipine or amlodipine) rather than verapamil
or diltiazem. Nicorandil is now often added as well, but again
there is not much evidence of added benefit. Coronary angiography
is indicated in patients who are potentially suitable for PCI
or CABG, and should be considered as an emergency in patients
who fail to settle on medical therapy.
ST-ELEVATION-MYOCARDIAL INFARCTION
(STEMI)
ACUTE MANAGEMENT
Oxygen
This is given in the highest concentration available (unless
there is coincident pulmonary disease with carbon dioxide
retention) delivered by face mask (FiO 2 approximately 60%) or
by nasal prongs if a face mask is not tolerated.
Pain relief
This usually requires an intravenous opiate (morphine or
diamorphine; see Chapter 25) and concurrent treatment with
an anti-emetic (e.g. promethazine or metoclopramide; see
Chapter 34).