MI L
Volume 8, No. 2
This Medicines Information Leaflet is produced locally to optimise the use of medicines by encouraging prescribing
that is safe, clinically appropriate and cost-effective to the NHS.
Guidance for pharmacological treatment in the early management of Acute Coronary
Syndromes: unstable angina and non-ST elevation myocardial infarction
T his guideline sets out pharmacological
treatment in the early management of
unstable angina (UA) and non-ST
elevation myocardial infarction (NSTEMI). It is
based on information within the National
Institute for Health and Clinical Excellence
(NICE) clinical guideline 94, the NICE
technology appraisal 236 and the European
Society of Cardiology guidelines.1, 2, 3
The management of ST-elevation myocardial
infarction (STEMI) involves primary
percutaneous coronary intervention and is not
covered by this guidance. These patients are
treated within the Oxford Heart Centre
according to local protocol.
Diagnosis of UA / NSTEMI is based on:
prolonged or new anginal chest pain
12 lead ECG showing ischaemic changes
e.g. ST segment depression or transient
elevation and/or T-wave changes
Troponin level
Classification: 1,2
NSTEMI: ST or T wave changes on the ECG
together with a rise in troponin level.
UA: Normal or undetermined ECG with a
normal troponin level.
Patients with a confirmed diagnosis of NSTEMI
or UA should be referred to the JR cardiology
registrar on call (bleep 4205). At the Horton,
the patient can be discussed with the onsite
Medicines Management and Therapeutics Committee
Oxford University Hospitals
June 2013
Cardiology consultant or the JR SpR depending
on clinical urgency and time of day.
Pharmacological Management
Initial supportive treatment
Administer oxygen if patient is hypoxic or if
there is evidence of pulmonary oedema.
Hyperoxia should be avoided in patients with
chronic obstructive airways disease. Give
sublingual glyceryl trinitrate to relieve
ischaemic chest pain. If pain continues give
intravenous morphine by slow injection
titrated to the pain (refer to injectable
monograph, the usual dose is 1 to 10mg, with
respiratory monitoring): Morphine injectable
monograph . An antiemetic such as
metoclopramide should also be given.
Antiplatelet agents
See appendix 1 for summary
Antiplatelet agents should only be
prescribed once the clinical diagnosis of
NSTEMI / UA has been confirmed.
The choice of antiplatelet agent depends
upon the diagnosis of NSTEMI or UA and
the patients risk of future cardiovascular
events, such as that predicted from the
Global Registry of Acute Cardiac Events
(GRACE) follow links below:
GRACE risk score
GRACE risk table
June 2013
 2 Medicines Information Leaflet
Unstable Angina:
Patients with a confirmed diagnosis of UA
e.g. ongoing chest pain, normal or
undetermined ECG and normal troponin
level should receive an oral loading dose of
aspirin 300mg and continue on a
maintenance dose of 75mg daily for life.
In addition, if predicted 6 month mortality
is greater than 1.5%, patients should
receive an oral loading dose of clopidogrel
300mg and continue on a maintenance
dose of 75mg daily for one year.
Selected high risk patients may be given
ticagrelor instead of clopidogrel (doses as
below) following advice from a Consultant
cardiologist only (as per NICE guidance).3
NSTEMI:
Patients should receive an oral loading
dose of aspirin 300mg and continue on a
maintenance dose of 75mg daily for life.
In addition, patients with a clear cut
diagnosis of NSTEMI following cardiology
review should receive an oral loading dose
of ticagrelor 180mg, unless contra-
indicated e.g. excessive bleeding risk,
active bleeding, history of intracranial
haemorrhage and continue on a
maintenance dose of 90mg twice a day for
one year (specify duration at discharge).
Where there is clinical uncertainty
between NSTEMI and UA, the patient
should be treated in the usual way with
aspirin and clopidogrel.
If the patient receives an initial loading of
aspirin and clopidogrel, the patient may be
subsequently switched to ticagrelor
following cardiology advice: stop
clopidogrel and give a loading dose of
ticagrelor 180mg and then continue on a
maintenance dose of 90mg twice a day.
Alternative antiplatelet agents
If a patient is intolerant to one antiplatelet
agent, they may be switched to an alternative
from those available e.g. clopidogrel, ticagrelor
or prasugrel. Contact the cardiology SpR for
further advice about alternatives.
Anticoagulant therapy
All patients with a confirmed diagnosis of ACS
particularly those with ECG changes indicative
of ischemia and/or troponin rise should be
prescribed fondaparinux (a factor Xa inhibitor),
unless they have a high bleeding risk. Factors
associated with a high bleeding risk include:
advancing age
known bleeding complications
renal impairment
low body weight (less than 50kg)
Use of fondaparinux in these patients should
be carefully considered. Contact the cardiology
SpR on call for further advice if necessary.
Patients prescribed fondaparinux for ACS do
not need any additional anticoagulant agent
e.g. dalteparin for VTE prophylaxis (a VTE risk
assessment still needs to be carried out).
The dose of fondaparinux for the treatment of
UA/NSTEMI is 2.5mg once daily administered
by subcutaneous injection. For practical
purposes a stat dose of fondaparinux may be
prescribed on the first day of treatment and
thereafter prescribed at 6pm to avoid any
complications with surgery or planned/
emergency angiograms (see below).
Treatment should be initiated as soon as
possible after diagnosis and continued for a
maximum of 8 days or until hospital discharge
if that occurs sooner. Refer to injectable
monograph for information on preparation
and administration.2,4
Fondaparinux injectable monograph
Renal and hepatic Impairment
Fondaparinux is contra-indicated in patients
with severe renal impairment (creatinine
clearance, CrCL, less than 20mL/min).4 Use
Cockcroft-Gault equation to calculate:
CrCl (mL/min) = F x (140-age) x weight* (kg)
Serum Cr (micromol/L)
F = 1 (females), F = 1.25 (males)
* Use ideal body weight (IBW) if actual body
weight (ABW) more than 20% above IBW (use
link below to calculate IBW)
IBW Calculator
 3 Medicines Information Leaflet
For patients with severe renal impairment,
consider using an intravenous unfractionated
heparin infusion, adjusting dose according to
the activated partial thromboplastin time
(APTT). Refer to the MIL on guidelines for use
of unfractionated heparin for further
information on prescribing, preparation and
administration of heparin infusions Medicines
Information Leaflet: Unfractionated heparin
Use fondaparinux with caution in patients with
severe hepatic impairment, as there is a lack of
information about the safety of its use in this
group of patients. 4
PCI and surgery
Do not give fondaparinux if a patient is due to
undergo a planned PCI the same day.
Unfractionated heparin, as a bolus injection (as
per local cardiac catheter lab protocol) should
be administered at the time of PCI in patients
pre-treated with fondaparinux. If the patient is
to undergo coronary bypass graft surgery
fondaparinux should be stopped, where
possible, 24 hours before surgery.
Fondaparinux and anticoagulation tests
At a dose of 2.5mg daily, the anticoagulant
effects of fondaparinux, cannot be detected by
routine anticoagulation tests such as
prothrombin time (PT), APPT, activated
clotting time (ACT) or international normalised
ratio (INR).
Secondary Prevention
Additional drugs for secondary prevention of
further myocardial infarction should be started
before discharge:
Bisoprolol - usual starting dose of 2.5mg
daily and gradually titrated upwards to
achieve a resting heart rate of 60 beats per
minute, as tolerated dependent on blood
pressure and heart rate (maximum dose
10mg daily). Use bisoprolol with caution in
patients with a history of asthma.
Ramipril - usual starting dose of 2.5mg
once a day (at night) and increased
depending on blood pressure after a few
days to 2.5mg twice daily. The dose should
be gradually titrated upwards to a
maximum of 5mg twice a day depending
on blood pressure. If the patient has severe
heart failure or low blood pressure, use a
starting dose of 1.25mg daily. Baseline
urea, electrolytes and creatinine should be
reviewed before starting an ACE inhibitor
and measured 1 to 2 weeks after starting
therapy to monitor renal function.
Angiotensin receptor blockers should only
be prescribed if the patient is intolerant or
allergic to ACE inhibitors.
Atorvastatin is the first line statin therapy.
Usual starting dose is 40mg to 80mg daily.
Baseline liver function tests (LFTs) should
be assessed before starting treatment. Do
not start statin treatment if LFTs are more
than 3 times the upper limit of normal.
Liver function tests should be monitored
periodically during treatment and therapy
stopped if the LFTs are persistently 3 times
the upper limit of normal.5
References
1. ESC guidelines for the management of acute coronary
syndromes in patients presenting without persistent ST-
segment elevation. Eur Heart J 2011: 32; 299903054
2. Unstable angina and NSTEMI. NICE clinical guideline 94
2010.
3. Ticagrelor for acute coronary syndromes. NICE TA 236
October 2011.
4. Fodaparinux (Atrixa). Summary of Product characteristics
accessed via eMC, last updated 29/12/2011
5. Atorvastatin (Wockhardt brand). Summary of product
characteristics accessed via eMC, last updated
21/09/2012
Prepared by: Jo Coleman, CTV Divisional Pharmacist; Jan
Keenan, Consultant Nurse Cardiology; Dr Sharman, Specialist
Cardiology Registrar; Chris Farmer Advanced Nurse
Practitioner, Chest Pain Cardiology; Dr R Kharbanda,
Consultant Cardiologist; Dr Forfar, Consultant Cardiologist; Dr
Myerson, Consultant Cardiologist and Dr Reynolds, Consultant
Acute General Medicine.
Review date: June 2016
 Appendix 1:
Summary of ACS guidelines (excluding STEMI)

Initiating treatment
There is no urgency to initiate antiplatelet and anticoagulant therapy until the diagnosis of
NSTEMI or UA has been established i.e. 2 out of the following 3 clinical signs are present:
continuing typical cardiac chest pain, ECG changes consistent with ischaemia or an elevated
troponin.

Do not initiate therapy in the presence of an isolated troponin rise in the absence of a suggestive
history or ECG changes. Elevation of troponin may occur in conditions other than STEMI and
NSTEMI where antiplatelet and anticoagulant therapy may be of no value and treatment may be
harmful. If, in doubt discuss with the on call cardiology team.

Important changes in initial ACS treatment:

Ticagrelor
All NSTEMI patients should be reviewed by a member of the cardiology team, usually the SpR
who will recommend appropriate therapy, including antiplatelet treatment.

Ticagrelor replaces clopidogrel as the second antiplatelet agent of choice in NSTEMI.

Loading dose is 180mg followed by a maintenance dose of 90mg twice a day for 1 year.

If a patient has been loaded with aspirin and clopidogrel they may be switched to ticagrelor, if
indicated, at any time: stop clopidogrel and give a loading dose of ticagrelor and then continue
with ticagrelor maintenance therapy.

Fondaparinux
Fondaparinux replaces dalteparin as the anticoagulant agent of choice in ACS.

Dose is 2.5mg by subcutaneous injection once a day.

Carefully consider use of fondaparinux in patients with a high bleeding risk.

Do not use in patients with severe renal impairment (creatinine clearance less than 20mL/min,
consider use of unfractionated heparin infusion in these patients.

The anticoagulant effects of fondaparinux cannot be detected by standard anticoagulation tests

e.g. PT, APPT, and INR.

Atorvastatin
Atorvastatin replaces simvastatin as the statin of choice in ACS

Medicines Management and Therapeutics Committee June 2013

Oxford University Hospitals
Summary flowchart of initial ACS management (excluding STEMI)

Patient admitted with probable

ACS

Confirmed diagnosis of NSTEMI:

chest pain, ECG changes and rise in
troponin level & cardiology review
fondaparinux 2.5mg subcutaneously
daily (maximum 8 days)
stat oral dose of aspirin 300mg and
Confirmed diagnosis of UA:
ticagrelor 180mg
chest pain ECG changes and
normal troponin level
stat oral dose of aspirin 300mg
Maintenance therapy: Consider fondaparinux 2.5mg
aspirin 75mg daily for life and subcutaneously daily
ticagrelor 90mg twice daily for If high risk patient
1 year (specify duration at discharge)

If predicted 6 month
Selected high risk patients
mortality greater
following cardiology
than 1.5% (GRACE):
advice only:
add clopidogrel
ticagrelor 180mg stat oral
stat oral dose 300mg
dose as an alternative to
clopidogrel

Maintenance therapy:
aspirin 75mg daily for life
and clopidogrel 75mg daily
for 1 year (specify duration
at discharge)
consider aspirin mono-
therapy in patients with less
than 1.5% 6 month
mortality risk (lowest risk)
Maintenance therapy:
aspirin 75mg daily
for life and ticagrelor 90mg
twice daily for
1 year (specify duration at
discharge)

Contact the JR cardiology registrar on call on bleep 4205 or one of the cardiac pharmacists on bleep
4288 / 1852 for further information

Medicines Management and Therapeutics Committee June 2013

Oxford University Hospitals