Download chapter 2 - Eastbourne, Hailsham and Seaford CCG

CHAPTER 2
First line drugs – drugs
recommended in both primary
and secondary care
CARDIOVASCULAR SYSTEM
Second line drugs –
alternatives (often in specific
conditions) in both primary
and secondary care
Specialist drugs – Drugs
where a specialist input is
needed (see introduction for
definition)
Specialist only drugs –
prescribing within specialist
service only
Page
2.1
Positive inotropic drugs
2
2.2
Diuretics
2
2.3
Anti-arrhythmic drugs
4
2.4
Beta-adrenoceptor blocking drugs
6
2.5
Drugs affecting the renin-angiotensin system and some other
antihypertensive drug
7
2.6
Nitrates, calcium-channel blockers, and potassium channel
activators
9
2.7
Sympathomimetics
11
2.8
Anticoagulants and reversal agents
11
2.9
Antiplatelet drugs
15
2.10
Myocardial infarction and fibrinolysis
16
2.11
Antifibrinolytic drugs and haemostatics
16
2.12
Lipid-lowering drugs
17
Date of revision
01/13
03/13
03/13
10/13
01/14
03/14
06/14
07/14
11/14
01/15
04/15
07/15
09/15
11/15
01/16
07/16
08/16
09/16
10/16
12/16
01/17
03/17
First line drugs
Revisions
1.3.5 (Updated MHRA Drug Safety), 2.8.2 (Updated guidance), 2.8.1
(Direct Healthcare Professional Communication)
2.6.3 (NICE guidance) 2.8 (NICE guidance)
2.8.2 (MHRA safety update)
2.8.2 (MHRA safety update)
2.4, 2.5, 2.9, 2.12 (NICE guidance)
2.9 (Minor amendment)
2.8.2 (Minor amendment)
2.9 (NICE guidance)
2.4 (NICE guidance), 2.8 (minor amendment)
2.11 (NICE guidance)
2.8 (NICE guidance)
2.8 (NICE guidance)
2.8 (NICE guidance)
2.8 (NICE guidance)
2.8 (NICE guidance)
2.5 (NICE guidance), 2.8 (Drug addition)
2.12 (NICE guidance)
2.6 (NICE guidance)
2.12 (NICE guidance), 2.5 (minor amendment)
2.8 (minor amendment)
2.2 (NICE guidance)
2.9 (Drug deletion), (NICE guidance)
Second line drugs
Specialist drugs
Contributors
A Luck
G Ells
A Luck
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
G Ells
Specialist only drugs
Page 1 of 20
2.1 Positive inotropic drugs
2.1.1
Cardiac glycosides
Digoxin



Tablets 62.5 micrograms, 125
micrograms, 250 micrograms
Elixir 50 micrograms/ml
Injection 100 micrograms in 1ml, 500
micrograms in 2ml
Occasionally necessary in hospital to treat
Digoxin toxicity
Digibind
Notes:
1. Digoxin toxicity signs: nausea and vomiting, diarrhoea, visual disturbances, confusion and delirium.
2. Initiation with digoxin therapy requires a loading dose (see BNF).
3. Annual monitoring of urea and electrolytes is important as electrolyte disturbances increase the risk of toxicity
from cardiac glycosides (Martindale Edition 32).
4. Serum levels should be assessed 7 – 14 days after adding or removing an interacting drug, and periodically,
according to the clinical picture. It is usually only necessary to monitor digoxin levels if there are signs or
symptoms present that suggest inadequate dose or drug toxicity.
5. Therapeutic drug monitoring: blood sample to be taken six to eleven hours post dose. Target is 1.0 to 2.60
nanomoles/litre (0.8 to 2.0 micro g/litre).
6. Plasma half-life is 30 to 50 hours. Time to steady state is 7 to 14 days.
2.1.2
Phosphodiesterase inhibitors
Milrinone

Injection 10mg in 10ml
Restricted to ITU only for use in unresponsive heart
failure
2.2 Diuretics
Please see NICE Clinical Guidelines CG 127 (December 2016) before starting anti-hypertensive medication.
Key priorities for implementation relating to drug treatment of hypertension include:
Initiating treatment
 Offer antihypertensive drug treatment to people aged under 80 years with stage 1 hypertension who have one or
more of the following:
− target organ damage
− established cardiovascular disease
− renal disease
− diabetes
− a 10-year cardiovascular risk equivalent to 20% or greater.
 Offer antihypertensive drug treatment to people of any age with stage 2 hypertension.
 For people aged under 40 years with stage 1 hypertension and no evidence of target organ damage,
cardiovascular disease, renal disease or diabetes, consider seeking specialist evaluation of secondary causes of
hypertension and a more detailed assessment of potential target organ damage. This is because 10-year
cardiovascular risk assessments can underestimate the lifetime risk of cardiovascular events in these people.
Choosing antihypertensive drug treatment
 Offer people aged 80 years and over the same antihypertensive drug treatment as people aged 55–80 years,
taking into account any comorbidities.
Step 1 treatment
 Offer step 1 antihypertensive treatment with a calcium-channel blocker (CCB) to people aged over 55 years and
to black people of African or Caribbean family origin of any age. If a CCB is not suitable, for example because of
oedema or intolerance, or if there is evidence of heart failure or a high risk of heart failure, offer a thiazide-like
diuretic.
 If a diuretic treatment is to be initiated or changed, offer a thiazide-like diuretic, such as chlortalidone (12.5–25.0
mg once daily) or indapamide (1.5 mg modified-release or 2.5 mg once daily) in preference to a conventional
thiazide diuretic such as bendroflumethiazide or hydrochlorothiazide.
 For people who are already having treatment with bendroflumethiazide or hydrochlorothiazide and whose blood
pressure is stable and well controlled, continue treatment with the bendroflumethiazide or hydrochlorothiazide.
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 2 of 20
Step 4 treatment
For treatment of resistant hypertension at step 4:
 Consider further diuretic therapy with low-dose spironolactone (25 mg once daily) if the blood potassium level is
4.5 mmol/l or lower. Use particular caution in people with a reduced estimated glomerular filtration rate because
they have an increased risk of hyperkalaemia.
 Consider higher-dose thiazide-like diuretic treatment if the blood potassium level is higher than 4.5 mmol/l.
Further detail of this guidance available here
The treatment of hypertension during pregnancy is outlined in:
NICE CG 107: Hypertension in pregnancy - The management of hypertensive disorders during pregnancy
2.2.1
Thiazide and related diuretics
Indapamide


Tablets 2.5mg
Tablets 1.5mg MR
Preferred over conventional thiazides
such as bendroflumethazide for
hypertension
Bendroflumethazide

Tablets 2.5mg
For resistant oedema / heart failure,
under specialist supervision
Chlorothiazide

Suspension 250mg in 5ml
Restricted to paediatrics only. Named
patient use only
Note:
1. NICE Clinical Guidelines CG 127 no longer recommends conventional thiazides such as
bendroflumethazide and hydrochlorthiazide to treat hypertension. Patients whose blood pressure is
stable and well controlled can, however, remain on these treatments until a change is clinically
warranted. Bendroflumethazide remains on the formulary for these patients and also for use as an.
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 3 of 20
2.
adjunct to loop diuretics in severe CCF and oliguria.
Indapamide 1.5mg MR is reserved for patients with abnormal electrolytes on 2.5mg standard
formulation.
2.2.2
Loop diuretics
Furosemide


Bumetanide

Tablets 20mg, 40mg, 500mg
Injection 20mg in 2 ml, 50mg in
5ml, 250mg in 25ml
Liquid 1mg in 1ml, 40mg in 5ml


Tablets 1mg, 5mg
Injection 2mg in 4ml
1mg/1ml paediatric use only
Notes:
1. Furosemide is the first line choice.
2. Bumetanide may be better absorbed than furosemide in patients with severe CCF.
3. Oral conversion: bumetanide 1mg = furosemide 40mg.
2.2.3
Potassium-sparing diuretics
Amiloride


Tablets 5mg
LiquidSF 5mg in 5ml
Spironolactone


Tablets 25mg, 50mg, 100mg
Suspension (1mg/1ml) 50mg/5ml
1mg/1ml paediatric use only
Eplerenone

Tablets 25mg
Heart failure post MI
Notes:
1. Routine co-prescribing of potassium sparing diuretics in combination with thiazide or loop diuretics should be reserved
as second line when the patient is stabilised, except in patients where hypokalaemia has been demonstrated or in
patients not taking an ACE inhibitor who are at risk from hypokalaemia e.g. those with severe CHD and arrhythmias
and those taking digoxin.
2. In severe heart failure, spironolactone added to other treatments in a low dose (e.g. 25mg daily) can reduce mortality
and morbidity. Careful monitoring for hyperkalaemia and hypovolaemia is required especially for people taking other
diuretics and / or ACE inhibitors.
3. Spironolactone is also included for specific indications e.g. ascites, nephrotic syndrome, primary hyperaldosteronism,
hypertension.
4. Eplerenone has outcome data for LVF post MI, but is much more expensive than spironolactone and there is no
comparative data for this indication.
2.2.4
Potassium-sparing diuretics with other diuretics
Fixed dose combinations of potassium sparing diuretics, for example, co-amilofruse (Frumil®, Frusene®) and coamilozide (Moduretic®) have NOT been considered as necessary in the formulary.
2.2.5
Osmotic diuretics
Mannitol

Used for cerebral oedema
Infusion 20% - 500 ml
2.3 Anti-arrhythmic drugs
Amiodarone
Atropine
Disopyramide
First line drugs




Tablets 100mg, 200mg
Injection 150mg in 3 ml
Pre-filled syringe 300mg in 10 ml

Pre-filled syringe 1mg/10 ml,
3mg/30ml
Injection 600mcg/1ml

Capsules 100mg


Tablets modified release 250mg
Injection 50mg in 5 ml
Second line drugs
Specialist drugs
Oral: Observe loading dose schedule
Specialist only drugs
Page 4 of 20
Dronedarone

Tablets 400mg Multaq®
Flecainide


Tablets 50mg, 100mg
Injection 150mg in 15 ml
Mexiletine
Propafenone
Sotalol
Adenosine

Capsules 50mg, 200mg

Tablets 150mg, 300mg

Tablets 40mg, 80mg

Injection 6mg in 2ml
IV infusion Adenoscan® 30mg in 10ml
Lidocaine


Infusion 1g in 5% Glucose (500 ml)
Injection (pre-filled syringe) 100mg in
5ml
Procainamide

Injection 100mg in 1ml

Note:
Amiodarone has a very long half-life (extending to several weeks). Following an oral loading dose (e.g. TDS for 1
week then BD for a further week) maintenance doses are administered ONCE DAILY.
Dronedarone has recently been licensed to treat adults with a history of or current non-permanent AF either to
prevent recurrence of AF or lower ventricular rate.
It has been compared with amiodarone in a clinical trial and found to be less effective than amiodarone but with
fewer adverse effects.
Dronedarone is considerably more expensive than standard treatments hence it should only be used in accordance
with NICE guidance (see below).
NICE Guidance: Dronedarone for the treatment of non-permanent atrial fibrillation (Technology Appraisal 197
Aug 2010)
Dronedarone is recommended as an option for the maintenance of sinus rhythm after successful cardioversion in
people with paroxysmal or persistent atrial fibrillation:
 whose atrial fibrillation is not controlled by first-line therapy (usually including beta-blockers), that is, as a
second-line treatment option and after alternative options have been considered and
 who have at least 1 of the following cardiovascular risk factors:
o hypertension requiring drugs of at least 2 different classes
o diabetes mellitus
o previous transient ischaemic attack, stroke or systemic embolism
o left atrial diameter of 50 mm or greater or
o age 70 years or older and
 who do not have left ventricular systolic dysfunction and
 who do not have a history of, or current, heart failure.
The MHRA Safety Update October 2011 advises that the benefits of using dronedarone now only outweigh the risks
in a limited population of patients with paroxysmal or persistent atrial fibrillation.
Dronedarone is now contraindicated in patients with:
 Unstable haemodynamic conditions


History of, or current, heart failure or left ventricular systolic dysfunction

Liver and lung toxicity related to previous use of amiodarone
Permanent AF (ie, duration ≥6 months or unknown, and attempts to restore sinus rhythm no longer considered by
physician)
The MHRA now recommends regular cardiac, hepatic, renal and pulmonary monitoring (see below)

Patients should receive regular cardiac examinations, including an ECG at least every 6 months, to identify those who
revert to AF. Discontinuation of dronedarone should be considered for these patients

Patients should be carefully evaluated for symptoms of heart failure during treatment

Liver-function tests should be done: before starting treatment with dronedarone; after 1 week of treatment; after 1 month of
treatment; then every month for 6 months; at month 9; at month 12; and periodically thereafter

Plasma creatinine values should be measured before and 7 days after initiation of dronedarone, and renal function should
be monitored periodically afterwards. Discontinue treatment in any patients with further elevations of serum creatinine

Cases of interstitial lung disease, including pneumonitis and pulmonary fibrosis, have been reported in association with
dronedarone. Onset of dyspnoea or non-productive cough may be related to pulmonary toxicity. If pulmonary toxicity is
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 5 of 20
suspected during treatment, relevant lung examinations should be considered and treatment discontinued if confirmed.
2.4 Beta-adrenoceptor blocking drugs
Beta blockers are no longer recommended as first line treatment for hypertension (see NICE algorithm, page 3).
Prescribing for new patients should follow NICE recommendations. Existing patients who are well controlled can be
maintained on beta blockers until review needed.




Tablets 25mg, 50mg, 100mg
Syrup 25mg/5ml
Injection 5mg in 10ml
Tablets 1.25mg, 2.5mg, 5mg, 7.5mg,
10mg
Not for new use first line in hypertension. Remains
useful in angina.
Labetalol


Tablets 100mg, 200mg, 400mg
Injection 100mg in 20 ml
Hypertension in pregnancy only
Propranolol

Thyrotoxicosis, migraine and anxiety only
Carvedilol




Tablets 10mg, 40mg, 80mg and 160
mg
Capsules M/R 80mg, 160mg
Mixture 50mg in 5ml
Injection 1mg in 1ml
Tablets 3.125mg, 6.25mg, 12.5mg,
Atenolol
Bisoprolol
Hypertension, angina and on specialist advice in
heart failure
Heart failure only
25mg
Metoprolol


Tablets 50mg, 100mg
Injection 5mg in 5ml
Angina
Nebivolol

Tablets 5mg
Heart failure only for patients aged over 70 years
Esmolol

Injection 100mg/10 ml, 2.5g/10ml
Notes:
1. Propranolol is included for the management of conditions such as thyrotoxicosis, migraine and anxiety only. Standard
formulations should be used first line. For patients where compliance might be a problem, the modified release (M/R)
formulation may be considered.
2. Labetalol may be used for the treatment of hypertension in pregnancy.
3. Sotalol is listed under anti-arrhythmic drugs as the CSM advises that its use should be limited to the treatment of
ventricular arrhythmias or prophylaxis of supraventricular arrhythmias.
4. Acebutolol maybe useful for the small number of patients with palpitations with slow resting heart rate, as it has intrinsic
sympathomimetic activity, but this use is unlicensed. Should be used under specialist supervision only.
For the treatment of acute heart failure, see NICE CG 187 (October 2014)
NICE CG108: Chronic heart failure - Management of chronic heart failure in adults in primary and secondary
care (Aug 2010)
This guidance outlines the diagnosis and treatment of chronic heart failure.
Notes on use of beta blockers in heart failure:
1. Beta-blockers should be considered for patients in controlled heart failure.
2. The NSF states that in people with controlled heart failure beta-blockers started in low doses can reduce mortality
when used with other treatments e.g. ACE inhibitors, diuretics and digoxin.
3. An appropriate specialist should initiate beta-blockers used in heart failure.
4. Nebivolol is only for heart failure patients aged over 70 years. The starting dose is 1.25mg for the first two weeks
and then if tolerated 2.5mg for two weeks, then 5mg from then on.
The following dose regimes are recommended for heart failure: (ref: BNF).
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 6 of 20
Bisoprolol
Carvedilol
Initially 1.25mg once daily (in the morning) for one week.
If well tolerated, increase to 2.5mg once daily for one week.
Then 3.75mg once daily for one week.
Then 5mg once daily for four weeks.
Then 7.5mg once daily for four weeks.
Then 10mg once daily.
Maximum dose is 10mg daily.
Initially 3.125mg twice daily (with food).
Dose increased at intervals of at least two weeks to 6.25mg
twice daily.
Then to 12.5mg twice daily.
Then to 25mg twice daily.
Increase to highest dose tolerated, maximum 25mg twice
daily in patients with severe heart failure or less than 85kg
body weight and 50mg twice daily in patients over 85kg.
Beta blockers are also recommended for secondary prevention post myocardial infarction (see CG172: Secondary
prevention in primary and secondary care for patients following a myocardial infarction Nov 2013)
2.5 Drugs affecting the renin-angiotensin system and some other antihypertensive drugs
2.5.1
Vasodilator antihypertensive drugs
Hydralazine

Tablets 25mg, 50mg
Sodium
Nitroprusside

50mg vial
Note:
1. Hydralazine, when used alone causes tachycardia and fluid retention.
2. In patients who are intolerant of ACE inhibitors or for whom they are contra-indicated, hydralazine may be used in
combination with long acting nitrates in moderate to severe chronic congestive cardiac failure, but this combination
may be poorly tolerated (BNF).
2.5.2
Centrally acting antihypertensive drugs
Methyldopa

Tablets 125mg
Moxonidine

Tablets 200 micrograms and 400
micrograms
Injection 150micrograms in 1ml

Used as an alternative where other agents have
caused side effects (4th line)
Notes:
Methyldopa is included for the treatment of hypertension in pregnancy only.
2.5.3
Adrenergic neurone blocking drugs
Guanethidine

Injection 10mg in 1ml
Notes:
1. Used for nerve blocks in pain management unit only.
2. No cardiovascular use.
2.5.4
Alpha-adrenoreceptor blocking drugs
Doxazosin
Phenoxybenzamine
Phentolamine

Tablets 1mg, 2mg, 4mg

Capsule 10mg

Injection 10mg in 1ml
See BNF chapter 7 for use in BPH
Notes:
1. NICE/BHS guidelines suggest doxazosin therapy is additional to other antihypertensive medications.
2. The 4mg modified release formulation of doxazosin is significantly more expensive but does reduce post dose
hypotension compared with the standard formulation.
3. In some patients it is safer to use the non-XL formulation bd to avoid this effect.
4. Following conversion from the XL formulation to the standard formulation, it is important to closely monitor blood
pressure
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 7 of 20
There are two possible strategies to convert patients from modified release to standard doxazosin:


In elderly patients, give half the dose of Cardura XL as standard doxazosin, i.e. 4mg XL switched to 2mg
standard od. It may then be possible to increase the dose to 2mg bd.
In younger patients, give the same dose as Cardura XL divided into a bd regime i.e. 4mg XL to 2mg bd standard.
Refer to BNF Chapter 7 for drugs used in the management of benign prostatic hyperplasia.
2.5.5
Drugs affecting the renin-angiotensin system
ACE inhibitors are recommended for secondary prevention post myocardial infarction (see CG172:
Secondary prevention in primary and secondary care for patients following a myocardial infarction Nov 2013)
2.5.5.1
Angiotensin-converting enzyme (ACE) inhibitors
Lisinopril

Tablets 2.5mg, 5mg, 10mg, 20mg
Ramipril

Capsules 1.25mg, 2.5mg, 5mg, 10mg
Perindopril

Tablets 2mg, 4mg, 8mg
See notes below
Notes:
1. First doses of ACE inhibitors may cause hypotension especially in patients taking high doses of diuretics, on a
low-sodium diet, on dialysis, dehydrated or with heart failure.
2. Renal function and blood pressure should be monitored before and during treatment and the dose reduced in
renal impairment. Monitor one week after initiating treatment, one week after a dose increase and otherwise
annually.
3. Whereas ramipril and perindopril have dual renal and hepatic excretion, lisinopril is solely renally excreted so
more care is needed if the patient has impaired renal function.
4. PROGRESS (Perindopril Protection against Recurrent Stroke Study) BMJ 2005 331:235-236. The benefits of
perindopril for the prevention of recurrent stroke are only proven in combination with a thiazide.
5. Perindopril should always be prescribed generically to avoid confusion with the branded product which is a
different salt and needs a dose adjustment.
6. Occasionally captopril is useful in hospital for patients in whom initiation of ACE inhibitors proves difficult.
7. If an ACE inhibitor is required in breastfeeding mothers, captopril or enalapril are the agents of choice but should
only be prescribed on the advice of a specialist.
2.5.5.2
Angiotensin-II receptor antagonists (ARBs)
N.B. Where indicated ACE inhibitors should be tried in all patients before considering an
Angiotensin II receptor antagonist
Candesartan
Irbesartan
Losartan

Tablets 2mg, 4mg, 8mg, 16mg
Outcome data for heart failure

Tablets 150mg, 300mg
Reno vascular protection, diabetes

Tablets 25mg, 50mg, 100mg
Hypertension with LVH
Valsartan

Tablets 40mg, 80mg
Sacubitril /valsartan▼

Entresto® tablets 24/26mg,
49/51mg, 97/103mg
Post MI when ACE inhibitor not tolerated
Notes:
1. No studies have shown that Angiotensin-II receptor antagonists are more effective than ACE inhibitors. They are
certainly more expensive. The first-choice renin-angiotensin system drug for people at high risk of CV disease,
with or without heart failure, is an ACE inhibitor.
2. Angiotensin-II receptor antagonists should be reserved for those patients on ACE inhibitors who suffer from
unacceptable cough, but cough can still occur with ARBs.
3. Candesartan is licensed for heart failure and valsartan post MI.
4. Combining an ACE inhibitor with an angiotensin-II receptor agonist for hypertension is not supported by efficacy
or safety data. The ONTARGET study suggests that adding an ARB to an ACE inhibitor in patients at high risk of
CV events, who do not also have heart failure, does not prevent adverse CV events. Indeed, using the
combination has been shown to increase the risk of adverse effects, serious enough to cause patients to stop
treatment.
5. Irbesartan has data for prevention of progression of existing renal disease in type II Diabetes Mellitus.
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 8 of 20
6. Losartan has outcome data in diabetic nephropathy and decreased risk of stroke in hypertension with LVH.
7. Monitoring requirements as per ACE inhibitors above.
8. Sacubitril valsartan is a combination neprilysin and angiotensin II receptor inhibitor for the treatment of
symptomatic chronic heart failure with reduced ejection fraction. It has been approved by NICE for use in
accordance with NICE TA 388: Sacubitril valsartan for treating symptomatic chronic heart failure with reduced
ejection fraction (April 2016)
NICE has recommended sacubitril valsartan as an option only in people:
 with New York Heart Association (NYHA) class II to IV symptoms
and
 with a left ventricular ejection fraction of 35% or less
and
 who are already taking a stable dose of angiotensin converting enzyme (ACE) inhibitors or angiotensin II
receptor blockers (ARBs).
Treatment with sacubitril valsartan should be started by a heart failure specialist with access to a multidisciplinary
heart failure team. Prescribing may be transferred to primary care after dose titration to the maximum (tolerated)
dose and once the patient is on a stable dose.
GPs will be informed that a patient has been initiated on sacubitril valsartan via the “Screening Checklist and
Notification of Initiation to GP” form. Once the patient is on a stable dose, GPs will be notified and asked to take
over prescribing using the “Transfer of Prescribing Responsibility” form. These forms can be found at
http://nww.esht.nhs.uk/clinical/cardiology/.
2.5.5.3
Renin inhibitors
Aliskiren

Tablets 150mg, 300mg
Notes:
1. Aliskiren is a direct inhibitor of renin, and targets the same system as ACE inhibitors and ARBs.
2. Data shows it to have similar efficacy to other antihypertensive drugs.
3. It may be used at Step 4 of the NICE/BHS hypertension guidelines (see page 3) where further diuretic, alpha
blocker or beta blocker therapy has not been effective or is contraindicated.
2.6 Nitrates, calcium-channel blockers, and potassium channel activators
2.6.1
Nitrates
Glyceryl trinitrate



Isosorbide
mononitrate




Spray 400 micrograms
Tablets 500 micrograms
Patches 5mg/24hours and
10mg/24hours
Buccal tablets 2mg, 3mg, 5mg
Injection 5mg in 5ml, 50mg in 10ml
Tablets 10mg, 20mg, 40mg
Modified release tablets (various
strengths available) see BNF
Notes:
1. NICE CG126: Stable angina: management
Offer people optimal drug treatment for the initial management of stable angina. Optimal drug treatment consists
of one or two anti-anginal drugs as necessary plus drugs for secondary prevention of cardiovascular disease.
2. Nitrate free periods can be achieved by prescribing ordinary release nitrates twice a day, first thing in the morning
and mid afternoon.
3. A modified release preparation (given once a day) may be useful to provide a nitrate free period where a patient
requires high doses of isosorbide mononitrate.
4. Modified release TABLETS are more cost effective than capsules therefore when modified release isosorbide
mononitrate is prescribed, use tablets, not capsules.
2.6.2
Calcium-channel blockers
Amlodipine
Adizem XL® or
Tildiem LA®

Tablets 5mg, 10mg

Once a day diltiazem longer acting
preparations
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 9 of 20
Adizem SR ® or
Tildiem Retard ®
Diltiazem

Twice a day diltiazem longer acting
preparations

Modified release tablets 60mg
administered twice or three times daily
Verapamil



Tablets 40mg, 80mg, 120mg, 160mg
Modified release tablets 120mg Half
Securon SR ®,
240mg Securon SR®
Injection 5 mg in 2 ml


Infusion 200mg/ml
Tablets 30mg
Nimodipine
Notes:
1. Specify the brand when prescribing a modified release diltiazem preparation (excluding 60mg tablet).
2. Specify the brand when prescribing a modified release verapamil preparation.
3. Verapamil is used where there is co-existing paroxysmal supraventricular tachycardia, or atrial fibrillation
±hypertension ± angina.
4. Verapamil has several significant drug interactions (see BNF for comprehensive list) including:
 β-blockers when asystole, severe hypotension and heart failure may ensue;
 digoxin where the plasma levels of digoxin may be increased, and there is risk of AV block and bradycardia.
5. Nimodipine is included for the prevention and treatment of ischaemic neurological deficits following subarachnoid
haemorrhage.
6. Although nifedipine has been removed from the formulary, patients currently taking nifedipine obtaining benefit
with no adverse effects, should remain on the product and not be switched.
2.6.3
Other antianginal drugs
Nicorandil

Tablets 10mg, 20mg
Ivabradine

Tablets 5mg, 7.5mg
Note:
1. Nicorandil has similar efficacy to other anti-angina drugs in controlling symptoms but there is little evidence about
its efficacy in combination with other anti-angina drugs. However, when added to maximal therapy with other antiangina drugs in refractory unstable angina (unlicensed indication) it may produce additional benefit.
2. Nicorandil is a potassium channel activator with nitrate properties; therefore additional nitrates may not be
needed.
3. Nicorandil is associated with a risk of gastrointestinal ulceration, including perianal ulceration. Although mouth
ulceration has long been recognised as a side-effect of nicorandil treatment, its use has more recently been
associated with ulceration of any region of the gastrointestinal tract including the perianal area. The ulceration is
commonly severe and, in a few patients, has led to perforation. Time to onset may vary widely. These ulcers are
refractory to treatment; they respond only to withdrawal of nicorandil, which should be done only under the
supervision of a cardiologist.
4. It is recommended that nicorandil should only be prescribed on the advice of a specialist or by someone with a
specialist interest.
5. Ivabradine may be useful for the symptomatic treatment of chronic stable angina pectoris in patients with normal
sinus rhythm, for whom heart rate control is desirable, and who have a contra-indication or intolerance for betablockers and rate-limiting calcium-channel blockers.
6. The ‘Beautiful’ study demonstrated ivabradine safety with significant LV dysfunction, in addition to a beta blocker.
With angina and impaired LV, ivabradine can be used in preference to a calcium antagonist.
7. NICE has approved the use of ivabradine as a treatment option for chronic heart failure in certain patients after a
four week stabilisation period on optimised standard treatments (TA267 Nov 2012)
2.6.4
Peripheral and cerebral vasodilators
NICE CG 147: Lower limb peripheral artery disease (August 2012) gives guidance on the diagnosis and
management of lower limb peripheral artery disease.
NICE has issued guidance on the use of vasodilators in peripheral artery disease (TA 223 May 2011)
 Only Naftidrofuryl oxalate is recommended as an option for the treatment of intermittent claudication in people
with peripheral arterial disease for whom vasodilator therapy is considered appropriate after taking into account
other treatment options.
 Treatment with naftidrofuryl oxalate should be started with the least costly licensed preparation.
 Patients should be assessed for improvements after 3 to 6 months
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 10 of 20
Naftidrofuryl oxalate

Capsules 100mg
2.7 Sympathomimetics
2.7.1
Inotropic Sympathomimetics
Dobutamine

2.7.2
Vasoconstrictor Sympathomimetics
Ephedrine

Injection 30mg in 1ml
Metaraminol

Injection 10mg in 1ml
Noradrenaline

Injection 4mg in 4ml
Phenylephrine

Injection 10mg in 1ml
2.7.3
Cardiopulmonary resuscitation
Epinephrine (rINN)

Injection 1mg in 10ml (Minijet®),

Injection 1mg in 1ml
Adrenaline (BAN)
Injection 250mg in 20ml
Note: Refer to BNF Chapter 3 for adrenaline used in the management of anaphylaxis.
2.8 Anticoagulants and reversal agents
2.8.1
Parenteral anticoagulants
Enoxaparin

Clexane® Pre-filled syringe for subcutaneous injection 100mg
in 1ml, 120mg in 0.8ml, 150mg in 1ml, 20mg in 0.2ml, 40mg
in 0.4ml, 60mg in 0.6ml, 80mg in 0.8ml
For use in unstable
angina and NSTEMI,
DVT and PE
Tinzaparin

Innohep® 10,000u/ml for prophylaxis DVT, 20,000 u/ml for
treatment of DVT and PE
For use in DVT and PE
Bivalirudin▼

Angiox® powder for reconstitution 250mg vial
Epoprostenol

Flolan® Infusion. Powder for reconstitution 500 micrograms
Fondaparinux
Heparin

Arixtra® Injection Pre-filled syringe 2.5mg in 0.5ml

Injection 2iu/ml in 500ml, 10iu/ml 5ml, 100iu/ml 2ml, 1000iu/ml 5ml
and 20ml, 5000iu/ml 5ml, 25,000iu/ml 0.2ml and 5ml
For use in unstable
angina and NSTEMI
1. The use of antiplatelet therapy, thrombolytics and anti-thrombin treatment in patients with unstable angina and
NSTEMI are covered in NICE CG 94: Unstable angina and NSTEMI
2. Bivalirudin is indicated for the treatment of STEMI in patients undergoing PCI when used in accordance with NICE
TA 230: Bivalirudin for the treatment of STEMI (Jul 2011)
3. Guidance for the prevention of VTE in patients admitted to hospital is detailed in NICE CG 92: Venous
thromboembolism - reducing the risks
Prophylaxis for VTE prevention should continue for 14 days post knee revision and 35 days post hip revision.
4. NICE CG 144: The management of venous thromboembolic diseases gives guidance on the care of adults
with VTE
5. Approved dosing regimens for Angiox (bivalirudin) for PCI following reports of inappropriate use. See Direct
Healthcare Professional Communication January 2013
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 11 of 20
2.8.2
Oral anticoagulants
Warfarin

Tablets 0.5mg, 1mg, 3mg, 5mg
Phenindione
Apixaban▼
Dabigatran▼

Tablets 10mg, 25mg, 50mg

Eliquis® 2.5mg, 5mg tablets
See below for indications

Pradaxa® capsules 75mg, 110mg,
150mg
See below for indications
Edoxaban▼
Rivaroxaban▼

Lixiana® tablets 15mg, 30mg, 60mg
See below for indications

Xarelto® tablets 2.5mg, 10mg, 15mg,
20mg
See below for indications
1. Phenindione may be used exceptionally when warfarin is not appropriate. (Licensed indications differ).
2. Nurse Specialist, Haemostasis and Thrombolysis, available at EDGH and Conquest
for
expert advice on request.
3. All prescribers have a responsibility to ensure awareness of any existing medications the patient may be taking
(including over the counter and herbal medicines) and the potential for interaction when prescribing
anticoagulants. All prescribers should ensure that their practice is compliant with the recommendations of the
NPSA Patient Safety Alert No.18: Actions that can make anticoagulant therapy safer
5. The formulary status of the oral thrombin inhibitors is dependent on the indication it is being used for – see table
below.
6. For appropriate dosing in renal impairment please consult the appropriate summary of product characteristics for
dabigatran, rivaroxaban, apixaban and edoxaban
7. Prophylaxis of venous thromboembolic events after elective hip and knee surgery
Apixaban, Dabigatran and Rivaroxaban are all approved by NICE for the prophylaxis of venous thromboembolic
events after elective hip and knee surgery as an alternative to low molecular weight heparins. No therapeutic
monitoring is required. Patients are discharged with the full course of treatment.
8. Prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation Apixaban,
Dabigatran, Edoxaban and Rivaroxaban are now licensed and approved by NICE to prevent stroke in patients
with atrial fibrillation with a CHA2DS2-VASC score of ≥2 or in males with a CHA2DS2-VASC score ≥ 1. Prescribing
should be in accordance with the approved treatment pathway below.
9. Acute DVT & PE treatment and VTE prophylaxis
Rivaroxaban is approved by NICE as a treatment option for the treatment of acute DVT or PE and prevention of
recurrent DVT and PE.
Dabigatran is approved by NICE as a treatment option for treatment and secondary prevention of DVT and PE
Apixaban is approved by NICE as a treatment option for treatment and secondary prevention of DVT and PE
Edoxaban is approved by NICE as a treatment option for treatment and secondary prevention of DVT and PE
10. Prevention of atherothrombotic events in acute coronary syndrome
Rivaroxaban in combination with aspirin and clopidogrel or aspirin alone is approved by NICE as a treatment
option for preventing further atherothrombotic events in patients with ACS. Prescribing responsibility will remain
with the cardiologists.
11. The MHRA drug Safety Update July 2012 gives updated advice on contraindications and warnings for
dabigatran and on switching treatment to and from dabigatran.
Dabigatran is contraindicated in clinical conditions associated with a significant risk of bleeding, such as:
current or recent gastrointestinal ulceration
oesophageal varices
malignant neoplasms
arteriovenous malformations
recent brain or spinal injury
vascular aneurysms
recent brain, spinal or ophthalmic surgery
major intraspinal or intracerebral vascular
recent intracranial haemorrhage
abnormalities
12. The benefits and risks of starting dabigatran should also be considered carefully for patients who may have other
conditions that put them at an increased risk of major bleeding (but in whom treatment with dabigatran is not
contraindicated)
13. The above has since been extended to include ALL new oral anticoagulants (apixaban, dabigatran and
rivaroxaban in MHRA Drug Safety update (October 2013)
14. Use of dabigatran is contraindicated with dronedarone, and with other anticoagulants, except when
switching treatment to or from dabigatran, or with the use of unfractionated heparin for maintenance of
venous or arterial catheter patency
15. Concomitant use of antiplatelet agents increases the risk of major bleeding with dabigatran approximately twofold, therefore a careful benefit-risk assessment should be made prior to initiation of treatment
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 12 of 20
16. Pradaxa® (dabigatran) is now contraindicated in patients with prosthetic heart valve requiring anti-coagulant
treatment. related to their valve surgery. This is regardless of the length of time elapsed since valve replacement
took place. The contraindication is based on clinical trial data which showed an increased frequency of
thromboembolic and bleeding events in the group of patients treated with dabigatran, compared with warfarin. See
Boehringer Ingelheim letter January 2013 and MHRA Drug Safety Update March 2013
Formulary status of NOACs
VTE prophylaxis (post
surgical
NB: Full course of
treatment to be
supplied by hospital
Stroke prevention in
AF
Apixaban
Dabigatran
Edoxaban
Rivaroxaban
Adults(18+) Eliquis®
2.5mg twice daily for 1014 days (knees) or 32-38
days (hips)
Adults (18 - 74):
Pradaxa® 110mg stat
then 220mg daily for 9
days (knees) or 27-34
days (hips)
Adults (75+): Pradaxa®
75mg stat then 150mg
daily for 9 days (knees)
or 27-34 days (hips)
N/A
Adults(18+):
Xarelto® 10mg daily
for 14 days (knees)
or 35 days (hips)
Adults (18+) Eliquis®
5mg twice a day
Adults (18-74):
Pradaxa® 150mg twice
daily
Adults (75+): Pradaxa®
110mg twice daily
Adults (18+):
Lixiana®
60mg once a day
In patients with one or
more of the following:
• Moderate or severe
renal impairment
(creatinine clearance
(CrCL) 15-50 mL/min)
• Low body weight ≤ 60
kg
• Concomitant use of
ciclosporin,
dronedarone,
erythromycin or
ketoconazole.
Lixiana® 30mg once a
day
After at least 5 days of
parenteral
anticoagulation: Adults
(18+): Lixiana®
60mg once a day.
Lixiana® 30mg once a
day in patients with
one or more risk
factors (see above)
Adults (18+):
Xarelto® 20mg daily
N/A
Adults (18+)
Xarelto® 2.5mg
twice daily in
combination with
aspirin/ aspirin +
clopidogrel.
Treatment for up to 1
year.
In patients with at least
two of the following
characteristics:

age ≥ 80 years,

body weight ≤ 60 kg

serum creatinine ≥
1.5 mg/dl (133
micromole/l).
Eliquis® 2.5mg twice a
day
DVT and PE acute
treatment & VTE
prophylaxis
Treatment of acute DVT
and treatment of PE
(Adults 18+): Eliquis®
10 mg twice daily for the
first 7 days followed by 5
mg twice daily for up to 6
months (see below)
Prevention of recurrent
DVT and PE (Adults 18+):
Eliquis® 2.5 mg twice
daily following completion
of 6 months of treatment
with Eliquis® 5 mg twice
daily or with another
anticoagulant (see SPC
for further information)
Prevention of
atherothrombotic
events in acute
coronary syndrome
First line drugs
N/A
Second line drugs
After at least 5 days of
parenteral
anticoagulation:
Adults (18-74):
Pradaxa® 150mg twice
daily
Adults (75-79):
Pradaxa® 110mg –
150mg twice daily
depending on pts
individual risk/benefit
Adults (80+) Pradaxa®
110mg twice daily
See SPC for other
groups where dose will
depend on individual
patient’s risk benefit ratio
N/A
Specialist drugs
Adults (18+)
Xarelto® 15mg
twice daily from days
1 to 21
Xarelto® 20mg daily
from day 22 onwards
Specialist only drugs
Page 13 of 20
Treatment Pathway – Prevention of stroke and systemic
embolism in adults with non-valvular atrial fibrillation
Assess risk of bleeding using the
HAS-BLED score and address
the following modifiable risk
2
factors where appropriate  Uncontrolled hypertension
 Poor INR control
 Concomitant drugs which
increase bleeding risk
 Harmful alcohol consumption
CHA2DS2-VASc score ≥ 2
or CHA2DS2-VASc score 1
1, 2
and male
Has the patient been
prescribed warfarin?
NO
3,4
YES
Explore reasons for
poor concordance
with the patient.
Revisit
anticoagulation
options including
no treatment, using
the NICE Patient
4
Decision Aid
NO
Informed discussion between
clinician and patient about the risks
and benefits of warfarin, apixaban,
dabigatran and rivaroxaban for that
patient. This must take into account
contraindications (e.g.renal & liver
5,6
function) , co-morbidities,
concomitant medication and
7
concordance .
Is the patient complying
with treatment?
(assess at ≥ 3 months)
YES
Does the patient have
good INR control? (TTR ≥
65%)
NO
Can the patient be
(re)considered for warfarin?
YES
NO
Continue on
warfarin
YES
Prescribe warfarin
Consider prescribing apixaban, dabigatran or rivaroxaban particularly in patients with:
7
- Poor INR control despite evidence they are complying
5
- Contraindications , allergy to or intolerable side effects from warfarin
1
From NICE CG 180 June 2014 available at: http://www.nice.org.uk/Guidance/CG180
Patients eligible for but not taking anticoagulants should have their stroke and bleeding risk reviewed annually.
3 Patient FAQs can be found at: http://nww.searchgpinfo-sussex.nhs.uk/prescribing/docs/2014/OAC_AF_FAQs
4 A patient decision aid can be found at http://guidance.nice.org.uk/CG180/PatientDecisionAid/pdf/English
5Many contraindications to warfarin also apply to the NOACs. Specialist advice may need to be sought before initiating warfarin–
contraindicated patients on apixaban, dabigatran or rivaroxaban.
6 Renal function should be assessed prior to the initiation of dabigatran and then at least once a year as needed. Monitoring of the
renal function of patients on apixaban and rivaroxaban at baseline and then at least once a year should be considered.
7 Poor concordance with warfarin is not an indication for initiating a NOAC as these drugs have shorter half-lives.
2
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 14 of 20
2.8.3
Protamine Sulphate
Protamine

Injection 50mg in 5ml
Used to treat overdosage of unfractionated or low molecular weight heparins
2.8.4
Idarucizumab
▼
Idarucizumab

Praxbind® Injection 2.5g in 50ml
Praxbind is a humanised monoclonal antibody fragment (Fab) that binds to dabigatran with very high affinity thereby
reversing its effect. It is indicated to rapidly reverse the effects of dabigatran for emergency surgery or urgent
procedures and in the event of life-threatening or uncontrolled bleeding. For use only in accordance with the protocol
Management of stroke
Alteplase is recommended by NICE to treat acute ischaemic stroke in adults. See NICE TA 264 for further
details.
2.9 Antiplatelet drugs
Aspirin
Clopidogrel
Dipyridamole

Dispersible tablets 75mg

Tablets 75mg


Tablets 100mg
Modified release capsules 200mg
Prasugrel

Tablets 5mg, 10mg
Ticagrelor

Tablets 90mg, 60mg
Abciximab
Eptafibitide

See protocols
To be used as adjunct to PTCA

See protocols
For high risk unstable angina
Notes:
1. Enteric-coated aspirin tablets are not recommended. There is no convincing evidence that at a daily dose of 75 mg
using enteric-coated rather than soluble aspirin reduces the risk of gastrointestinal bleeding. (Ref: DTB Jan 1997 p7-8).
2. The use of clopidogrel with low dose aspirin is recommended for up to 1 year after acute coronary syndromes,
up to 1 year after drug eluting stent insertion and up to 3 months after bare metal stenting and occasionally for
longer at the discretion of the operator.
3. Current evidence demonstrates that after one year of clopidogrel with low dose aspirin, the risks of continued
treatment outweigh the benefits.
4. See NICE CG 94 (March 2010) Unstable angina and NSTEMI and CG172: Secondary prevention in primary
and secondary care for patients following a myocardial infarction Nov 2013 for further information.
5. Clopidogrel should NOT be substituted for aspirin, where patient has GI discomfort or bleed. Gastroprotection
with PPI should be considered (lansoprazole 15mg capsules).
6. Prasugrel (Efient®) is an antiplatelet agent with a similar mode of action to clopidogrel.
7. It is licensed for use in conjunction with aspirin for the prevention of atherothrombotic events in patients with acute
coronary syndrome (i.e., unstable angina, non-ST segment elevation myocardial infarction [UA/NSTEMI] or ST
segment elevation myocardial infarction [STEMI]) undergoing primary or delayed percutaneous coronary
intervention (PCI).
8. In certain patient groups it has demonstrated superior efficacy to clopidogrel but at a cost of an increased risk of
major bleeding.
9. It is administered as a 60mg loading dose with a maintenance dose of 10mg daily for up to 12 months. A 5mg
daily maintenance dose is recommended for individuals weighing less than 60kg.
10. NICE TA 317 (July 2014): Prasugrel 10 mg in combination with aspirin is recommended as an option for
preventing atherothrombotic events in adults with acute coronary syndrome (unstable angina [UA], non-ST
segment elevation myocardial infarction [NSTEMI] or ST segment elevation myocardial infarction [STEMI]) having
primary or delayed percutaneous coronary intervention.
11. Ticagrelor (Brilique®) is a new antiplatelet agent licensed for use in combination with aspirin to prevent
atherothrombotic events after acute coronary syndrome.
12. In studies ticagrelor was found to be more effective at preventing further atherothrombotic events than clopidogrel
but at the expense of an increased risk of bleeding and increased incidence of dypsnoea.
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 15 of 20
13. Initiation must be undertaken by a cardiologist. GPs may prescribe continuation of treatment on the advice of the
specialist for up to 12 months.
14. NICE TA 260: Ticagrelor for the treatment of acute coronary syndromes (ACS) (Oct 2011) recommends that:
Ticagrelor 90mg in combination with low-dose aspirin is recommended for up to 12 months as a treatment option
in adults with acute coronary syndromes (ACS) that is, people:
 with ST-segment-elevation myocardial infarction (STEMI) – defined as ST elevation or new left bundle branch
block on electrocardiogram – that cardiologists intend to treat with primary percutaneous coronary intervention
(PCI)
or
 with non-ST-segment-elevation myocardial infarction (NSTEMI)
or
 admitted to hospital with unstable angina – defined as ST or T wave changes on electrocardiogram
suggestive of ischaemia plus one of the characteristics defined in section 1.2.
Before ticagrelor is continued beyond the initial treatment, the diagnosis of unstable angina should first be
confirmed, ideally by a cardiologist.
15. NICE TA 420: Ticagrelor for preventing atherothrombotic events after myocardial infarction (December
2016)
Ticagrelor 60mg, in combination with aspirin, is recommended within its marketing authorisation as an option for
preventing atherothrombotic events in adults who had a myocardial infarction and who are at high risk of a further
event.
Treatment should be stopped when clinically indicated or at a maximum of 3 years
16. Ticagrelor has a twice daily dosage regime.
17. NICE TA 210: Clopidogrel and modified release dipyridamole for the prevention of occlusive vascular
events (review of TA 90) (Dec 2010)
NICE has recommended that:
Clopidogrel is an option to prevent occlusive vascular events:
 For people who have had an ischaemic stroke, have peripheral arterial disease or multivascular disease;
or
 For people who have had a myocardial infarction only if aspirin is contra-indicated or not tolerated
The combination of MR dipyridamole and aspirin is used as part of the prevention of occlusive vascular events in
people who have had
 a transient ischaemic attack;
or
 an ischaemic stroke if clopidogrel is contraindicated or not tolerated
Modified release dipyridamole alone is an option to prevent occlusive vascular events
 For people who have had an ischaemic stroke only if aspirin and clopidogrel are contraindicated or not
tolerated;
or
 For people who have had a transient ischaemic attack only if aspirin is contraindicated or not tolerated.
MHRA Drug Safety Update – Interaction between the use of clopidogrel and PPI’s – April 2010
In light of the most recent evidence, the previous advice on the concomitant use of clopidogrel with proton
pump inhibitors has now been modified. Use of either omeprazole or esomeprazole with clopidogrel should
be discouraged. The current evidence does not support extending this advice to other PPIs.
2.10 Myocardial infarction and fibrinolysis
2.10.1
Fibrinolytic drugs
Streptokinase
Tenecteplase
Urokinase

Injection 1.5 million units
See ESHT guidelines

30 – 50mg according to body weight
See ESHT guidelines

10,000 unit vial
2.11 Antifibrinolytic drugs and haemostatics
Tranexamic Acid
Aprotinin
Etamsylate
First line drugs
 Tablets 500mg

50ml vial

Tablets 500mg
Second line drugs
Specialist drugs
Specialist only drugs
Page 16 of 20
2.12 Lipid-lowering drugs

Tablets 10mg
Bezafibrate

Fenofibrate

(Bezalip mono®) Modified Release
Tablets 400mg
Supralip® 160 Tablets 160mg
Ezetimibe
NB: Licensed for use in primary
hypercholesterolaemia and homozygous
familial hypercholesterolaemia
Fibrates
Specialist input should be sought when prescribing a fibrate in combination with a statin
Statins
Atorvastatin

Tablets 10mg, 20mg, 40mg, 80mg
Simvastatin

Tablets 20mg, 40mg,
Rosuvastatin

Crestor® Tablets 5mg, 10mg, 20mg,
40mg
On specialist recommendation: for treatment of
familial hypercholesterolaemia and in patients
intolerant to 3 other statins
Omega-3 fatty acid compounds
Omega-3-acid
Ethyl Esters

On specialist recommendation for treatment of
hypertriglyceridaemia
Omacor® capsules
Reduction in Low density lipoprotein cholesterol
Dose (mg/day)
5
10
20
40
80
27%1
33%2
Fluvastatin
-
-
21%1
Pravastatin
-
20%1
24%1
29%1
-
Simvastatin
-
27%1
32%2
37%2
42%3,4
Atorvastatin
-
37%2
43%3
49%3
55%3
Rosuvastatin
38%2
43%3
48%3
53%3
-
1
20% - 30%: low intensity
31% - 40%: medium intensity
3 above 40%: high intensity
4 Advice from the MHRA: there is an increased risk of myopathy associated with high-dose (80 mg)
simvastatin. The 80 mg dose should be considered only in patients with severe hypercholesterolaemia and
high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when
the benefits are expected to outweigh the potential risks.
2
See NICE guidance CG181 (July 2014) Lipid modification: cardiovascular risk assessment and modification of
blood lipids for the primary and secondary prevention of cardiovascular disease
The decision whether to start statin therapy should be made after an informed discussion between the clinician and
the person about the risks and benefits of statin treatment, taking into account additional factors such as potential
benefits from lifestyle modifications, informed patient preference, comorbidities, polypharmacy, general frailty and life
expectancy.
1. Offer atorvastatin 20mg for primary prevention of CVD to people who have a 10% or greater 10-year risk of
developing CVD. Estimate the level of risk using the QRISK2 assessment tool
2. For people 85 years or older consider atorvastatin 20mg for primary prevention as statins may be of benefit in
reducing the risk of non-fatal myocardial infarction. Be aware of factors that may make treatment inappropriate
(see above).
3. Start statin treatment in people with CVD with atorvastatin 80mg. Use a lower dose of atorvastatin if any of the
following apply:
a. potential drug interactions
b. high risk of adverse effects
c. patient preference
4. Consider statin treatment for the primary prevention of CVD in all adults with type 1 diabetes.
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 17 of 20
5. Offer statin treatment for the primary prevention of CVD to adults with type 1 diabetes who:
a. are older than 40 years or
b. have had diabetes for more than 10 years or
c. have established nephropathy or
d. have other CVD risk factors.
6. Start treatment for adults with type 1 diabetes with atorvastatin 20mg
7. Offer atorvastatin 20mg for the primary prevention of CVD to people with type 2 diabetes who have a 10% or
greater 10-year risk of developing CVD. Estimate the level of risk using the QRISK2 assessment tool.
8. Offer atorvastatin 20mg for the primary or secondary prevention of CVD to people with CKD.
a. Increase the dose if a greater than 40% reduction in non-HDL cholesterol is not achieved (see
recommendation 1.3.28) and eGFR is 30 ml/min/1.73 m2 or more.
b. Agree the use of higher doses with a renal specialist if eGFR is less than 30 ml/min/1.73 m 2.
9. Measure total cholesterol, HDL cholesterol and non-HDL cholesterol in all people who have been started on highintensity statin treatment at 3 months of treatment and aim for a greater than 40% reduction in non-HDL
cholesterol. If a greater than 40% reduction in non-HDL cholesterol is not achieved:
a. discuss adherence and timing of dose
b. optimise adherence to diet and lifestyle measures
10. Consider increasing dose if started on less than atorvastatin 80 mg and the person is judged to be at higher risk
because of comorbidities, risk score or using clinical judgement.
Advice and monitoring for adverse effects
1. Advise people who are being treated with a statin:
a. that other drugs, some foods (for example, grapefruit juice) and some supplements may interfere with
statins and
b. to always consult the patient information leaflet, a pharmacist or prescriber for advice when starting
other drugs or thinking about taking supplements.
2. Remind the person to restart the statin if they stopped taking it because of drug interactions or to treat intercurrent
illnesses.
3. Before offering a statin, ask the person if they have had persistent generalised unexplained muscle pain, whether
associated or not with previous lipid-lowering therapy. If they have, measure creatine kinase levels.
a. If creatine kinase levels are more than 5 times the upper limit of normal, re-measure creatine kinase
after 7 days. If creatine kinase levels are still 5 times the upper limit of normal, do not start statin
treatment.
b. If creatine kinase levels are raised but less than 5 times the upper limit of normal, start statin
treatment at a lower dose.
4. Advise people who are being treated with a statin to seek medical advice if they develop muscle symptoms (pain,
tenderness or weakness). If this occurs, measure creatine kinase.
5. Measure baseline liver transaminase enzymes (alanine aminotransferase or aspartate aminotransferase) before
starting a statin. Measure liver transaminase within 3 months of starting treatment and at 12 months, but not again
unless clinically indicated.
6. Do not routinely exclude from statin therapy people who have liver transaminase levels that are raised but are less
than 3 times the upper limit of normal.
7. Do not stop statins because of an increase in blood glucose level or HbA1c.
8. Statins are contraindicated in pregnancy
Intolerance of statins
1. If a person is not able to tolerate a high-intensity statin aim to treat with the maximum tolerated dose.
2. The following strategies can be tried to manage adverse events:
a. stop the statin and try again when the symptoms have resolved to check if the symptoms are related to
the statin
b. reduce the dose within the same intensity group
c. change the statin to a lower intensity group.
Interactions
Statins may differ in terms of their pharmacology and interactions with other drugs. Simvastatin has been the
subject of a Drug Safety Update (August 2012) which reports contraindications and maximum dose
recommendations when taken in combination with specific drugs.
Rosuvastatin should only be used on the advice of a lipid clinic specialist in the following situations:

Patients with familial hypercholesterolaemia (FH) not achieving the 50% reduction target specified in NICE
CG71: Identification and management of familial hypercholesterolaemia (which may also include FH
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 18 of 20
patients who cannot tolerate atorvastatin)


Patients who have CVD or who are at high risk of CVD who have tried and are intolerant to 3 different statins
after seeking advice from a specialist (which could be e-mail or telephone advice)
Specific patients with complex co-morbidities referred to the lipid clinic and on specialist advice
NICE TA 385 (Feb 2016): Ezetimibe for treating primary heterozygous-familial and non-familial
hypercholesterolaemia
1.
Ezetimibe monotherapy is recommended as an option for the treatment of adults with primary (heterozygousfamilial or non-familial) hypercholesterolaemia who would otherwise be initiated on statin therapy (as per NICE
guidance CG181) but who are unable to do so because of contraindications to initial statin therapy.
2.
Ezetimibe monotherapy is recommended as an option for the treatment of adults with primary (heterozygousfamilial or non-familial) hypercholesterolaemia who are intolerant to statin therapy.
3.
For the purposes of this guidance, intolerance to initial statin therapy should be defined as the presence of
clinically significant adverse effects from statin therapy that are considered to represent an unacceptable risk to
the patient or that may result in compliance with therapy being compromised. Adverse effects include evidence of
 new-onset muscle pain (often associated with levels of muscle enzymes in the blood indicative of muscle
damage),
 significant gastrointestinal disturbance
 alterations of liver function tests.
4.
Ezetimibe, coadministered with initial statin therapy, is recommended as an option for the treatment of adults with
primary (heterozygous-familial or non-familial) hypercholesterolaemia who have been initiated on statin therapy
(as per NICE guidance CG181) when:

serum total or low-density lipoprotein (LDL) cholesterol concentration is not appropriately controlled either
after appropriate dose titration of initial statin therapy or because dose titration is limited by intolerance to the
initial statin therapy
and

consideration is being given to changing from initial statin therapy to an alternative statin.
5.
For the purposes of this guidance, appropriate control of cholesterol concentrations should be based on
individualised risk assessment in accordance with national guidance on the management of cardiovascular
disease for the relevant populations.
6.
When the decision has been made to treat with ezetimibe co-administered with a statin, ezetimibe should be
prescribed on the basis of lowest acquisition cost.
Additional guidance
1. NICE guidance on Identification and management of familial hypercholesterolaemia (CG71 Aug 2008
rev Jul 2016)
2. CG172: Secondary prevention in primary and secondary care for patients following a myocardial
infarction Nov 2013
PCSK9 inhibitors
Alirocumab▼

Praluent® Solution for injection, 75mg,
150mg PFS, Pen
▼
 Repatha® Solution for injection,
Evolocumab
140mg PFS, Pen
NICE has approved the use of the monoclonal antibodies, Alirocumab and Evolocumab to treat patients with
primary hypercholesterolaemia or mixed dyslipidaemia where LDL-C concentrations remain above the threshold
specified in the table below despite maximal tolerated lipid lowering therapy.
These treatments are self-administered by subcutaneous injection every 2 weeks.
Assessment, initiation, prescribing and monitoring of these treatments is through lipid clinics only.
LDL-C concentrations above which alirocumab and evolocumab are recommended
Without CVD
With CVD
High risk of CVD 1
Primary non-familial
Not recommended at any Recommended only if
hypercholesterolaemia or
LDL-C concentration
LDL-C concentration is
mixed dyslipidaemia
persistently above
First line drugs
Second line drugs
Specialist drugs
Very high risk of CVD 2
Recommended only if
LDL-C concentration is
persistently above
Specialist only drugs
Page 19 of 20
4.0 mmol/litre
3.5 mmol/litre
Recommended only if LDL-C concentration is
persistently above 3.5 mmol/litre
Primary heterozygous-familial Recommended only if
hypercholesterolaemia
LDL-C concentration is
persistently above
5.0 mmol/litre
1 High risk of CVD is defined as a history of any of the following: acute coronary syndrome (such as myocardial
infarction or unstable angina needing hospitalisation); coronary or other arterial revascularisation procedures; chronic
heart disease; ischaemic stroke; peripheral arterial disease.
2 Very
high risk of CVD is defined as recurrent cardiovascular events or cardiovascular events in more than 1 vascular
bed (that is, polyvascular disease).
Abbreviations: CVD, cardiovascular disease; LDL-C, low-density lipoprotein cholesterol.
First line drugs
Second line drugs
Specialist drugs
Specialist only drugs
Page 20 of 20