page135
used,
eplerenone (section 2.2.3) may be considered for
the management
of
heart
failure after an acute myo-
cardial
infarction with evidence of
left ventricular sys-
tolic dysfunction. Close monitoring of serum creatinine,
eGFR,
and potassium is necessary,
particularly follow-
ing any change in treatment
or
any change in the
patient’s clinical condition.
Patients who cannot
tolerate an ACE inhibitor
or
an
angiotensin-II receptor antagonist, or in whom they are
contra-indicated,
may be given isosorbide dinitrate
(section 2.6.1)
with hydralazine (section 2.5.1),
but
this combination may be poorly tolerated.
In patients
of African or Caribbean origin, and those with moderate
to severe heart
failure,
the combination of
isosorbide
dinitrate and hydralazine may be considered in addition
to standard therapy with an ACE inhibitor and a beta-
blocker,
if necessary.
Digoxin (section 2.1.1)
improves symptoms of
heart
failure and exercise tolerance and reduces hospitalisa-
tion due to acute exacerbations but it does not reduce
mortality. Digoxin is reserved for patients with worsen-
ing or severe heart failure due to left ventricular systolic
dysfunction who remain symptomatic despite treatment
with an ACE inhibitor and a beta-blocker in combination
with either an aldosterone antagonist,
candesartan,
or
isosorbide dinitrate with hydralazine.
Patients with fluid overload should also receive either a
loop or a thiazide diuretic (with salt or fluid restriction
where appropriate).
A thiazide diuretic (section 2.2.1)
may be of benefit in patients with mild heart failure and
good renal
function;
however,
thiazide diuretics
are
ineffective in patients with poor renal
function (eGFR
less
than 30 mL/minute/1.73 m
2
,
see Renal
Impair-
ment,
section 2.2.1) and a loop diuretic (section 2.2.2)
is preferred.
If diuresis with a single diuretic is insuffi-
cient,
a combination of
a loop diuretic and a thiazide
diuretic may be tried;
addition of
metolazone (section
2.2.1) may also be considered but the resulting diuresis
may be profound and care is needed to avoid potentially
dangerous electrolyte disturbances.
2.5.5.1
Angiotensin-converting enzyme
inhibitors
Angiotensin-converting enzyme inhibitors
(ACE inhi-
bitors) inhibit the conversion of angiotensin I to angio-
tensin II.
They have many uses and are generally well
tolerated.
The main indications of
ACE inhibitors are
shown below.
Heart failure
ACE inhibitors are used in all grades of
heart
failure,
usually combined with a beta-blocker
(section 2.5.5).
Potassium supplements and potassium-
sparing diuretics should be discontinued before introdu-
cing an ACE inhibitor because of
the risk of
hyperkal-
aemia.
However,
a low dose of spironolactone may be
beneficial in severe heart failure (section 2.5.5) and can
be used with an ACE inhibitor provided serum potas-
sium is monitored carefully.
Profound first-dose hypo-
tension may occur when ACE inhibitors are introduced
to patients with heart failure who are already taking a
high dose of a loop diuretic (e.g. furosemide 80 mg daily
or
more).
Temporary withdrawal
of
the loop diuretic
reduces the risk,
but may cause severe rebound pulm-
onary oedema. Therefore, for patients on high doses of
loop diuretics,
the
ACE inhibitor
may need to be
initiated under
specialist
supervision,
see below.
An
ACE inhibitor
can be initiated in the community in
patients who are receiving a low dose of
a diuretic or
who are not
otherwise at
risk of
serious hypotension;
nevertheless, care is required and a very low dose of the
ACE inhibitor is given initially.
Hypertension
An ACE inhibitor
may be the most
appropriate initial
drug for
hypertension in younger
Caucasian
patients;
Afro-Caribbean
patients,
those
aged over 55 years, and those with primary aldosteron-
ism respond less well
(see section 2.5).
ACE inhibitors
are particularly indicated for hypertension in patients
with type 1 diabetes with nephropathy (see also section
6.1.5). They may reduce blood pressure very rapidly in
some patients particularly in those receiving diuretic
therapy (see Cautions,
below);
the first
dose should
preferably be given at bedtime.
Diabetic nephropathy
For comment on the role of
ACE inhibitors in the management of diabetic nephro-
pathy,
see section 6.1.5.
Prophylaxis of
cardiovascular events
ACE inhi-
bitors are used in the early and long-term management
of
patients who have had a myocardial
infarction,
see
section 2.10.1.
ACE inhibitors may also have a role in
preventing cardiovascular events.
Initiation under specialist supervision
ACE inhi-
bitors should be initiated under specialist
supervision
and with careful clinical monitoring in those with severe
heart failure or in those:
.
receiving multiple or
high-dose diuretic therapy (e.g.
more than 80 mg of furosemide daily or its equivalent);
.
with hypovolaemia;
.
with
hyponatraemia
(plasma-sodium concentration
below 130 mmol/litre);
.
with
hypotension
(systolic
blood
pressure
below
90 mmHg);
.
with unstable heart failure;
.
receiving high-dose vasodilator therapy;
.
known renovascular disease.
Renal effects
Renal
function and electrolytes should
be checked before starting ACE inhibitors (or increasing
the dose)
and monitored during treatment
(more fre-
quently if features mentioned below present); hyperkal-
aemia and other side-effects of ACE inhibitors are more
common in those with impaired renal function and the
dose may need to be reduced (see Renal
impairment
below and under individual drugs).
Although ACE inhi-
bitors now have a specialised role in some forms of renal
disease,
including chronic kidney disease,
they also
occasionally cause impairment of renal
function which
may progress
and become severe in other
circum-
stances (at particular risk are the elderly).
A specialist
should be involved if
renal
function is
significantly
reduced as a result of treatment with an ACE inhibitor.
Concomitant treatment with NSAIDs increases the risk
of
renal
damage,
and potassium-sparing diuretics (or
potassium-containing salt substitutes) increase the risk
of hyperkalaemia.
In patients with severe bilateral renal artery stenosis (or
severe stenosis of the artery supplying a single function-
ing kidney), ACE inhibitors reduce or abolish glomerular
filtration and are likely to cause severe and progressive
renal
failure.
They are therefore not
recommended in
BNF 61
2.5.5 Drugs affecting the renin-angiotensin system
115
2
Cardiovascular system