Clinical Pharmacology and Therapeutics

DRUGS USED TO TREAT DYSLIPIDAEMIA 183
reduced). The risk of muscle damage is increased if they are
taken with a statin, although lipid specialists sometimes
employ this combination. They can cause a variety of gastrointestinal
side effects, but are usually well tolerated.
Contraindications
Fibrates should be used with caution, if at all, in patients with
renal or hepatic impairment. They should not be used in
patients with gall-bladder disease or with hypoalbuminaemia.
They are contraindicated in pregnancy and in alcoholics
(this is particularly important because alcohol excess
causes hypertriglyceridaemia; see Table 27.1).
Pharmacokinetics
Bezafibrate and gemfibrozil are completely absorbed when
given by mouth, highly protein bound, and excreted mainly
by the kidneys.
OTHER DRUGS
Other drugs sometimes used by lipidologists are summarized
in Table 27.2. These include nicotinic acid which needs to be
administered in much larger doses than needed for its effect as
a B vitamin (Chapter 35). Its main effects on lipids are distinctive,
namely to increase HDL, reduce TG and reduce Lp(a).
Unfortunately, it has troublesome adverse effects including
flushing (mediated by release of vasodilator prostaglandin
D 2 ) which is reduced by giving the dose 30 minutes after a
dose of aspirin.
Key points
Treatment of dyslipidaemia
• Treatment goals must be individualized according to
absolute risk. Patients with established disease need
treatment irrespective of LDL.
• Dietary measures involve maintaining ideal body
weight (by caloric restriction if necessary) and reducing
consumption of saturated fat – both animal (e.g. red
meat, dairy products) and vegetable (e.g. coconut oil) –
as well as cholesterol (e.g. egg yolk).
• Drug treatment is usually with a statin (taken once
daily at night) which is effective, well tolerated and
reduces mortality. Consider the possibility of secondary
dyslipidaemia.
• Ezetimibe is well tolerated. It is a useful adjunct to a
statin in severely dyslipidaemic patients who show an
inadequate response to a statin alone, and has almost
completely replaced bile acid binding resins for this
indication.
• Fibrates are useful as a first-line treatment in patients
with primary mixed dyslipidaemias with high
triglyceride concentrations, as well as high LDL (and
often low HDL). Avoid in alcoholics.
• Other reversible risk factors for atheroma (e.g.
smoking, hypertension) should be sought and treated.
• Consideration should be given to adjunctive use of
aspirin as an antiplatelet/antithrombotic drug.
Case history
A 36-year-old male primary-school teacher was seen because
of hypertension at the request of the surgeons following
bilateral femoral artery bypass surgery. His father had died
at the age of 32 years of a myocardial infarct, but his other
relatives, including his two children, were healthy. He did
not smoke or drink alcohol. He had been diagnosed as
hypertensive six years previously, since which time he had
been treated with slow-release nifedipine, but his serum
cholesterol level had never been measured. He had been
disabled by claudication for the past few years, relieved
temporarily by angioplasty one year previously. There were
no stigmata of dyslipidaemia, his blood pressure was
150/100 mmHg and the only abnormal findings were those
relating to the peripheral vascular disease and vascular surgery
in his legs. Serum total cholesterol was 12.6 mmol/L,
triglyceride was 1.5 mmol/L and HDL was 0.9 mmol/L. Serum
creatinine and electrolytes were normal. The patient was
given dietary advice and seen in clinic four weeks after discharge
from hospital. He had been able to run on the games
field for the first time in a year, but this had been limited by
the new onset of chest pain on exertion. His cholesterol level
on the diet had improved to 8.0 mmol/L. He was readmitted.
Questions
Decide whether each of the following statements is true or
false.
(a) This patient should receive a statin.
(b) Coronary angiography is indicated.
(c) Renal artery stenosis should be considered.
(d) The target for total cholesterol should be 6.0 mmol/L.
(e) Ezetimibe would be contraindicated.
(f) An α 1 -blocker for his hypertension could
coincidentally improve his dyslipidaemia.
(g) His children should be screened for dyslipidaemia and
cardiovascular disease.
Answer
(a) True.
(b) True.
(c) True.
(d) False.
(e) False.
(f) True.
(g) True.
Comment
It was unfortunate that this young man’s dyslipidaemia was
not recognized earlier. Coronary angiography revealed severe
inoperable triple-vessel disease. The target total cholesterol
level should be 5.0 mmol/L and was achieved with a
combination of diet, a statin at night and ezetimibe in
the morning. Renal artery stenosis is common in the setting of
peripheral vascular disease, but renal angiography was negative.
This patient’s relatively mild hypertension was treated
with doxazosin (a long-acting α 1 -blocker, see Chapter 28)
which increases HDL, as well as lowering blood pressure. He
probably has heterozygous monogenic familial hypercholesterolaemia
and his children should be screened. One of his
sons is hypercholesterolaemic and is currently being treated
with a combination of diet and a statin.
FURTHER READING
Durrington PN. Dyslipidaemia. Lancet 2003; 362: 717–31.
Durrington PN. Hyperlipidaemia: diagnosis and management, 3rd edn.
London: Hodder Arnold, 2005.