page177
An ACE inhibitor (section 2.5.5.1) should be considered
for all
patients,
especially those with evidence of
left
ventricular dysfunction.
If
an ACE inhibitor cannot be
used, an angiotensin-II receptor antagonist may be used
for patients with heart failure.
A relatively high dose of
either
the
ACE inhibitor
or
angiotensin-II
receptor
antagonist may be required to produce benefit.
Nitrates
(section 2.6.1)
are
used for
patients
with
angina.
Eplerenone (section 2.2.3) is licensed for use following
a myocardial
infarction in those with left
ventricular
dysfunction and evidence of heart failure.
For the role of
statins in preventing recurrent cardio-
vascular events,
see section 2.12.
2.10.2
Fibrinolytic drugs
Fibrinolytic drugs act
as thrombolytics by activating
plasminogen to form plasmin,
which degrades fibrin
and so breaks up thrombi.
The value of
thrombolytic drugs for the treatment
of
myocardial
infarction
has
been established (section
2.10.1).
Streptokinase
and
alteplase
have
been
shown to reduce mortality. Reteplase and tenecteplase
are
also
licensed
for
acute
myocardial
infarction.
Thrombolytic drugs are indicated for any patient with
acute myocardial
infarction for
whom the benefit
is
likely to outweigh the risk of
treatment.
Trials have
shown that
the benefit
is greatest
in those with ECG
changes that include ST segment elevation (especially in
those with anterior
infarction)
and in patients
with
bundle branch block.
Patients should not
be denied
thrombolytic
treatment
on
account
of
age
alone
because mortality in the elderly is high and the reduc-
tion in mortality is the same as in younger patients.
Alteplase,
reteplase and streptokinase need to be given
within 12 hours of symptom onset, ideally within 1 hour;
use after 12 hours requires specialist advice.
Tenecte-
plase should be given as early as possible and usually
within 6 hours of symptom onset.
Alteplase, streptokinase, and urokinase can be used for
other
thromboembolic
disorders
such as
deep-vein
thrombosis and pulmonary embolism.
Alteplase is also
used for acute ischaemic stroke (see section 2.9).
Urokinase is also licensed to restore the patency of
occluded intravenous catheters and cannulas blocked
with fibrin clots.
Cautions
Thrombolytic drugs should be used with
caution if
there is
a risk of
bleeding including that
from venepuncture or invasive procedures. They should
also be used with caution in external chest compression,
elderly,
hypertension, conditions in which thrombolysis
might
give
rise
to embolic
complications
such as
enlarged left
atrium with atrial
fibrillation (risk of
dis-
solution of
clot
and subsequent
embolisation),
and
recent
or
concurrent
use of
drugs that
increase the
risk of bleeding.
Contra-indications
Thrombolytic drugs are contra-
indicated in recent
haemorrhage,
trauma,
or
surgery
(including dental extraction), coagulation defects, bleed-
ing diatheses,
aortic dissection,
aneurysm,
coma,
his-
tory of cerebrovascular disease especially recent events
or
with any residual
disability,
recent
symptoms
of
possible
peptic
ulceration,
heavy
vaginal
bleeding,
severe hypertension,
active pulmonary disease with
cavitation,
acute
pancreatitis,
pericarditis,
bacterial
endocarditis,
and oesophageal
varices;
also in the case
of
streptokinase,
previous allergic reactions to either
streptokinase or anistreplase (no longer available).
Prolonged persistence of
antibodies to streptokinase
and anistreplase (no longer available)
can reduce the
effectiveness
of
subsequent
treatment;
therefore,
streptokinase should not be used again beyond 4 days
of
first
administration
of
either
streptokinase
or
anistreplase.
Hepatic impairment
Thrombolytic drugs should be
avoided in severe hepatic impairment
as there is an
increased risk of bleeding.
Pregnancy
Thrombolytic drugs can possibly lead to
premature separation of
the placenta in the first
18
weeks of
pregnancy.
There is also a risk of
maternal
haemorrhage throughout
pregnancy and post-partum,
and also a theoretical risk of fetal haemorrhage through-
out pregnancy.
Side-effects
Side-effects of thrombolytics are mainly
nausea and vomiting and bleeding. When thrombolytics
are used in myocardial
infarction,
reperfusion arrhyth-
mias and recurrent
ischaemia and angina may occur.
Reperfusion may also cause cerebral
and pulmonary
oedema. Hypotension can also occur and can usually be
controlled by elevating the patient’s legs, or by reducing
the rate of infusion or stopping it temporarily. Back pain,
fever,
and convulsions have been reported.
Bleeding is
usually limited to the site of injection,
but intracerebral
haemorrhage or
bleeding from other
sites can occur.
Serious bleeding calls for discontinuation of the throm-
bolytic and may require administration of
coagulation
factors and antifibrinolytic drugs (e.g. tranexamic acid).
Rarely further embolism may occur (either due to clots
that break away from the original
thrombus or to cho-
lesterol crystal emboli).
Thrombolytics can cause aller-
gic reactions (including rash,
flushing and uveitis) and
anaphylaxis has been reported (for details of
manage-
ment see Allergic Emergencies, section 3.4.3). Guillain-
Barre
´
syndrome has been reported rarely after strepto-
kinase treatment.
ALTEPLASE
(rt-PA, tissue-type plasminogen activator)
Indications
acute myocardial infarction (see notes
above and section 2.10.1);
pulmonary embolism;
acute ischaemic stroke (treatment under specialist
neurology physician only)
Cautions
see notes above;
in acute stroke
, monitor for
intracranial haemorrhage,
monitor blood pressure
(antihypertensive recommended if systolic above
180 mmHg or diastolic above 105 mmHg)
Contra-indications
see notes above;
in acute stroke
,
convulsion accompanying stroke,
severe stroke,
his-
tory of stroke in patients with diabetes, stroke in last 3
months,
hypoglycaemia,
hyperglycaemia
Hepatic impairment
see notes above
Pregnancy
see notes above
Side-effects
see notes above;
also risk of cerebral
bleeding increased in acute stroke
BNF 61
2.10.2 Fibrinolytic drugs
157
2
Cardiovascular system