ELMMB logo
Facebook logo Twitter logo
Menu
2.0 Cardiovascular

2.0 Cardiovascular

2.1.1 Cardiac glycosides

Most useful in the treatment of supraventricular tachycardias, especially for controlling ventricular response in atrial fibrillation.

GREEN      Digoxin      
                   tablets 62.5 microgram, 125 microgram, 250 microgram  
                      elixir 50microgram/mL

RED           Digoxin injection 250microgram/mL


2.1.2 Phosphodiesterase inhibitors

RED           Milrinone injection 10mg/10mL
RED           Enoximone injection 5mg/mL


Hypokalaemia may occur with thiazides and loop diuretics. The risk is greater with thiazides as they have a longer duration of action. Use of a potassium sparing diuretic can usually avoid the need for potassium supplement.

2.2.1 Thiazides and related diuretics

GREEN      Bendroflumethiazide  tablets 2.5mg         
GREEN      Indapamide
                   tablets 2.5mg
                  tablets MR 1.5mg

N.B. where Bendroflumethiazide is to be used for oedema or where an alternative to Metolazone (discontinued by manufacturer) is needed, Bendroflumethiazide 5mg tablets would be suitable.       

2.2.2Thiazides Loop Diuretics

First line treatment  
GREEN       Furosemide        
                  tablets 20mg, 40mg    
                   liquid 50mg in 5mL  
AMBER      Furosemide tablets 500mg
 
RED            Furosemide injection 20mg/2mL, 50mg/5mL, 250mg/25mL

Second line treatment - Only if poor response to furosemide      
GREEN       Bumetanide      
                   tablets 1mg, tablets 5mg       
                      liquid 1mg/5mL         


Metolazone
–an unlicensed tablet is available and is approved for inclusion in formulary for secondary care use only
.  

RED            Metolazone tablets (unlicensed secondary care only)                  

2.2.3 Potassium-sparing diuretics and aldosterone antagonists

Amiloride on its own is a weak diuretic. It causes retention of potassium and is used as a more effective alternative to giving potassium supplements with thiazide or loop diuretics.

Spironolactone is licensed only for congestive cardiac failure, hepatic cirrhosis with ascites and oedema, malignant ascites, nephrotic syndrome and the diagnosis and treatment of primary aldosteronism.

Both of these drugs have the potential to cause hyperkalaemia with drugs acting on the renin-angiotensin system.

GREEN      Amiloride  
                   tablets 5mg   
                   liquid 5mg/5mL
GREEN      Spironolactone   
                   tablets 25mg, 100mg
RED             Spironolactone  
                   liquid 5mg/5mL, 10mg/5mL, 25mg/5mL, 50mg/5ml, 100mg/5mL  for NICU use only 

Eplerenone                                                                                                                                                                                                 For patients with symptoms and/or signs of heart failure and left ventricular systolic dysfunction (LVSD), initiate treatment with eplerenone, an aldosterone antagonist.  Eplerenone is licensed for post-MI treatment within 3–14 days of the MI, preferably after ACE inhibitor therapy.  For patients with clinical heart failure and LVSD already being treated with an aldosterone antagonist for a concomitant condition (e.g. spironolactone), continue with the aldosterone antagonist or an alternative, licensed for early post-MI treatment. 

Assessment/monitoring                                                                                                                                                                     Monitor renal function and serum potassium before and during treatment. If hyperkalaemia is a problem, halve the dose or stop the treatment.

AMBER      Eplerenone
                   tablets 25mg, 50mg 

2.2.4 Potassium-sparing diuretics with other diuretics

Fixed dose combinations may be justified where compliance is a problem.

GREEN      Co-amilofruse (amiloride, furosemide)       
                   tablets 2.5/20, 5/40

2.2.5 Osmotic diuretics

RED           Mannitol intravenous infusion 10%, 20%

Management of arrhythmia, apart from the treatment associated with heart failure, requires precise diagnosis of the type of arrhythmia and electrocardiography is essential.

2.3.2 Drugs for arrhythmias

In the management of arrhythmias, beta-blockers should also be considered.

Supraventricular arrhythmias 

RED           Adenosine injection 6mg/2mL

Digoxin      see section 2.1.1

Verapamil  see section 2.6.2

Dronedarone

Appraised by NICE in TA197 (August 2010) as follows:

Before starting treatment with dronedarone, prescribers should perform liver function tests. Tests should be repeated monthly for six months, at months 9 and 12, and periodically thereafter.  Prescribers should stop treatment with dronedarone in patients with raised levels of the liver enzyme alanine aminotransferase (more than three times above the upper limit of normal). Appropriate investigation and close observation of patients should continue until the enzyme levels return to normal.  For further information go to MHRA Drug Safety Update February 2011

MHRA Drug Alert (October 2011) advises of new evidence of cardiovascular, hepatic and pulmonary risk associated with use of dronedarone, such that regular monitoring of cardiac, liver and renal function is recommended during treatment and that patients should be reviewed at their next routine appointment to ensure that they remain eligible for dronedarone treatment according to the revised prescribing information. 

AMBER     Dronedarone tablets f/c 400mg

Supraventricular and ventricular arrhythmias

AMBER     Amiodarone 
                  tablets 100mg, 200mg
RED           Amiodarone     
                  injection 150mg/3mL
                  pre-filled syringe 300mg in 10mL
AMBER     Flecainide tablets 100mg
RED           Flecainide injection 150mg/15mL

Ventricular arrhythmias 

RED           Lidocaine / lignocaine
                   Min-I-Jet® 2% (20mg/mL) (5mL)
                   Infusion 0.1% (1mg/mL) and 0.2% (2mg/mL) in glucose intravenous infusion 5% (500mL containers)  

For angina:                                                                                                                                         Atenolol is relatively cardioselective and more water soluble (less likely to enter the brain). Pindolol has intrinsic sympathomimetic activity.  Atenolol is also used following myocardial infarction. 

GREEN      Atenolol
                   tablets 25mg, 50mg, 100mg     
                   syrup 25mg/5mL    
RED           Atenolol injection 5mg/10mL
AMBER     Pindolol tablets 5mg (initiation by Cardiologist only)    

Labetalol has additional vasodilating action and is also used for hypertensive crisis. Suitable for hypertension in pregnancy, but it may cause neonatal hypoglycaemia.

AMBER     Labetalol tablets 100mg, 200mg   
RED           Labetalol injection 100mg/20mL


Arrhythmias:                                                                                                                                     Esmolol is relatively cardioselective with a short duration of action, sotalol is non-cardioselective and used for prophylaxis.

RED           Esmolol injection 10mg/mL (10mL & 250mL)
AMBER     Sotalol tablets 40mg, 80mg      
 


Alternative short acting beta blocker to assess response in high risk patients 

GREEN     Metoprolol 50mg. 100mg tablets

Heart failure:                                                                                                                                     Only clinicians confident in the management of patients with heart failure should consider beta-blocker initiation. Although beta-blockers in heart failure have been given a GREEN traffic light by the Medicines Management Board (MMB), those with little experience of managing this patient group should consider referring appropriate patients to the specialist HF service for advice, in accordance with local referral pathways.

Patients in whom beta-blockers should be initiated with particular caution include:  
>  Those with reversible airways disease - refer to a HF specialist for advice.
> Those with recent evidence of fluid overload, or patients with repeated episodes of fluid overload 
  - may require additional diuresis, consider referral to a HF specialist for advice. 
Bisoprolol is the preferred agent in primary care, with carvedilol a suitable second line alternative. These agents should be initiated at the lowest dose within the dose range. An ECG should be considered before initiation in patients with a heart rate < 60 beats per minute or where atrial fibrillation is suspected.             

The beta-blocker dose should be increased cautiously over a period of three or more months to the maximal tolerated dose within the dose range, in order to achieve a resting heart rate between 50 and 60 beats per minute. Fluid status, heart rate and blood pressure should be assessed prior to and following each dose change. Patients may experience more heart failure-related symptoms during initiation and dose titration of beta-blockers. Additional diuresis may be required to manage symptoms of fluid overload. Patients should be encouraged to persist with therapy, as evidence demonstrates improved quality of life in the longer term, as well as reduced mortality and hospitalisation. 

NICE Algorithm for the use of beta-blockers in heart failure  (ref: CG108, August 2010)

Confirmed left ventricular systolic dysfunction (Ejection fraction <40% on ECHO)

Step 1 Assess whether suitable for treatment
   º   Contraindicated in asthma, severe COPD, Heart block, Sick Sinus Syndome
   º   Clinically stable Heart Failure (NYAI-VI)
   º   No signs of sodium and water retention (oedema, lung crackles, raised JVP or congestion on CXR or             hepatic congestion)
   º   Commence on patient who is already receiving duiretic & ACE inhibitor
   º    If on Beta-blocker for concommitant condition to continue on their current Beta-blocker or one                   alternatively licensed for heart failure.
   º  Heart rate >60 bpm perform ECG
   º  Systolic BP > 100mmHg


Step 2 - Suitable for Beta-blocker  
   º  Start low and slow
   º   Monitor heart rate, BP & clinical status (symptoms, signs, especially signs of congestion, body weight)   

Step 3 - Two weeks later 
   º   Check blood electrolytes, urea & creatinine 1-2 weeks after initiation and 1-2 weeks after final dose 
        titration.
   º   Continue  to monitor Heart rate, BP, clinical status (symptoms, signs, especially signs of congestion
   º   Aim for target dose or, failing that, the highest tolerated dose

Bisoprolol dose 
      >   1.25mg daily for at least one week  
      >   2.5mg daily for at least one week
      >   3.75mg daily for at least one week
      >   5mg daily for at least one week
      >   7.5mg daily for at least one week
      >   10mg thereafter
 
Carvedilol dose 
      >   3.125mg twice daily for a minimum of 2 weeks
      >   6.25mg twice daily for a minimum of 2 weeks
      >   25mg twice daily maintenance for those weighing <85kg & if severe heart failure
      >   50mg maintenance dose for those weighing >85kg with mild to moderate heart failure
 
Advice to patients  
      >   Explain expected benefits
      >   Emphasise that treatment given as much to prevent worsening of heart failure as to                                         improve symptoms; beta-blockers also increase survival
      >   If symptomatic improvement occurs, this will be slowly (3 -6 months)
      >   Temporary symptomatic deterioration may occur (20-30% cases during initiation/up                                         titration)


Problem solving
      >   Worsening symptoms/signs (e.g. dyspnoea, fatigue, oedema, weight gain) for                                                     immediate review
      >   If increasing congestion, double dose of diuretic/halve dose of beta-blocker if diuretic does not                    work
      >   if marked fatigues and/or bradycardia halve dose of beta-blocker
      >   Review 1-2 week: if not improved seek specialist advice
      >   if serious deterioration, before stopping treatment seek specialist advice.


GREEN
      Bisoprolol tablets 1.25mg, 2.5mg, 3.75mg, 5mg, 7.5mg, 10mg

GREEN       Carvedilol tablets 3.125mg, 6.25mg, 12.5mg, 25mg

Non-cardiac use: Propranolol is not recommended for cardiac indications but has an application in management of migraine (see section 4.7) 

5.1 Vasodilator antihypertensive drugs

Potent drugs. Hydralazine is a useful adjunct to other treatment. 
GREEN      Hydralazine tablets 25mg, 50mg 
RED           Hydralazine injection 20mg 
RED           Sodium nitroprusside intravenous infusion 50mg/5mL
 
Pulmonary arterial hypertension
Sildenafil and bosentan are licensed for use in pulmonary arterial hypertension (PAH).  Treatment of this condition is
commissioned nationally through a small number of PAH centres based in hospitals across the UK.  All patients should
be referred to one of these centres, who carry out all prescribing of these therapies through a home delivery company
Funding for treatment will be authorised by the patients CCG prior to initiation by a PAH centre. The nearest PAH 
centre is at the Royal Hallamshire Hospital, Sheffield.
 
RED           Bosentan tablets 62.5mg, 125mg 
RED           Sildenafil tablets 20mg (Revatio® brand, NOT Viagra®)      
 

2.5.2 Centrally acting antihypertensive drugs

Not widely used, but may be useful in pregnancy and asthma. Moxonidine to be used in resistant hypertension only.
GREEN       Methyldopa tablets 125mg, 250mg, 500mg 
AMBER       Moxonidine tablets 200microgram, 300microgram, 400microgram
 

2.5.4 Alpha-adrenoceptor blocking drugs

Doxazosin also has vasodilator properties. It is a fourth-line choice of antihypertensive only –  see NICE guideline on 
hypertension.
GREEN      Doxazosin tablets 1mg, 2mg, 4mg
 
The use of doxazosin m/r is not recommended. In hospital, all prescriptions for doxazosin m/r will be changed to
standard release tablets as above.
 
Phaeochromocytoma
Phenoxybenzamine is used in its management
AMBER     Phenoxybenzamine capsules 10mg  
RED           Phenoxybenzamine injection 100mg/2 mL
 

2.5.5 Drugs affecting the renin-angiotensin system 

2.5.5.1 Angiotensin-converting enzyme inhibitors

For hypertension, heart failure, immediate and long term management post MI. For heart failure and MI aim to 
increase lisinopril to 30mg/day and ramipril to 10mg/day to gain maximum effects.
GREEN      Lisinopril tablets 2.5mg, 5mg, 10mg, 20mg     
GREEN      Ramipril capsules 1.25mg, 2.5mg, 5mg, 10mg 
 
Perindopril is restricted to use in hypertension for secondary prevention of stroke. It should be administered as a 
single daily dose 30 minutes before breakfast in order to minimise considerable variations in bioavailability.

GREEN      Perindopril tablets 2mg, 4mg  

Enalapril 
(reduction of proteinuria in children with nephritis - Paediatrics use only) 
AMBER      Enalapril tablets 2.5mg
 
Post-natal Hypertension only  
AMBER      Enalapril tablets 2.5mg , 5mg, 10mg 
 

2.5.5.2 Angiotensin-II receptor antagonists

Do not use first line.  Use only if cough is troublesome on ACE inhibitors but bear in mind that cough may be a
symptom of cardiac failure. Improvement in ACE inhibitor related cough can be expected within four weeks of 
stopping therapy.  Check product licenses in BNF before prescribing as they differ between products.
 
Heart failure or hypertension 
First Line 
GREEN      Losartan tablets 12.5mg, 25mg, 50mg, 100mg 
Second Line (to be used when patient is intolerant of Losartan) 
GREEN      Candesartan tablets 2mg, 4mg, 8mg, 16mg
 
Diabetic nephropathy in type II diabetes mellitus 
First Line  
GREEN      Irbesartan tablets 75mg, 150mg, 300mg      
 
Monitoring hypertension and post MI  
       >     Assess LV function in all patients who have had an MI.
       >     Monitor BP, renal function and serum electrolytes:
              >     before starting an ACE/ARB and within 1 to weeks,
              >     after each dose increase
              >     periodically once the dose is stable; annually is suggested, but more often if at risk of deterioration in
                     renal function.

AMBER      Sacubitril valsartan (Entresto®) 24 mg/26 mg,49 mg/51 mg,97mg/103 mg film-coated tablets 
                   (heart failure specialist only)
 
As an option in NICE TA388  for treating symptomatic chronic heart failure with reduced ejection fraction, only  
in people: 
            >     with New York Heart asscoiation (NYHA) class II to IV symptoms and 
            >     with a left venticular 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)    
 
2.5.5.3 Renin Inhibitors 
Aliskiren  (Rasilez®) 
          >     Aliskiren should NOT be initiated in primary care. It should only be initiated by a consultant with experience 
                 in managing resistant essential hypertension.
          >     NICE recommends the use of beta-blockers, alpha blockers or additional diuretics as current fourth line 
                 treatments. Where patients are being managed in primary care, and blood pressure remains uncontrolled 
                 on adequate doses of four drugs, and expert advice has not yet been obtained, this should now be sought.
          >     Aliskiren should only be used as a fifth line treatment, where NICE recommended fourth line treatments are 
                 ineffective, inappropriate or not tolerated. Use should be restricted to resistant hypertension or for patients 
                 with nephrotic syndrome who can't tolerate an ACE or ARB. Following initiation or recommendation by the
                 specialist, prescribing may be transferred to the primary care prescriber. It should not be used in women of
                 child bearing potential.
          >     Aliskiren can be used in combination with other anti-hypertensives. Routine monitoring of electrolytes and 
                 renal function is indicated when used with an ACE inhibitor or angiotensin receptor blocker (ARB), or when
                 used in kidney dysfunction, diabetes mellitus or heart failure.
          >     Aliskiren should not be used for the acute management of severe or malignant hypertension as effects on 
                 blood pressure are only attained after 1-2 weeks of treatment.
 
Fifth Line
AMBER     Aliskiren f/c tablets 150mg, 300mg
 
Chronic Kidney Disease NICE CG182
Monitoring ACEI/ARB treatment in CKD only
Test eGFR and serum potassium before starting treatment, 102 weeks later and after each dose increase.
 
Potassium  
          >     Monitor more frequently if the patient is taking other drugs that cause hyperkalaemia
          >     If serum potassium >5.0mmol/L:
                      >     do NOT start ACEIs/ARBs
                      >     Investigate and treat other factors known to cause hyperkalaemia then recheck serum potassium.
         >     If serum potassium >6.0mmol/L: STOP ACEIs/ARBs  
 
eGFR and serum creatinine
          >     If there is a decrease in eGFR <25% or an increase in serum creatinine <30%
                      >     do NOT change the dose,
                      >     repeat test after 1-2 weeks.
          >     If the eGFR decrease is > 25% or serum creatinine increase  30% 
                      >     investigate other causes,
                      >     if no other cause: STOP ACEI/ARB or reduce dose,
                      >     Add alternative anti hypertensive if required.

2.6.1 Nitrates

GREEN         Glyceryl trinitrate 
                     tablets sublingual 500 microgram 
                     buccal tablets 2mg, 5mg
                     aerosol spray 400micrograms/dose  
                     patches 5mg/24hr, 10mg/24hr
RED             Glyceryl trinitrate injection 25mg/5ml, 50mg/50mL
 
Isosorbide mononitrate M/R    
Standard release preparations have been replaced with the following modified release (M/R) products. 
These should be prescribed by brand. A guide detailing how to switch from standard formulation to modified release
preparations can be found here.
 
GREEN        Chemydur® XL 60mg tablets,   
                     Monomil XL 60mg tablets,   
                     Elantan LA 25mg, 50mg capsules  
 

2.6.2 Calcium-channel blockers

Amlodipine is for angina and hypertension, has a longer duration of action and can be given once a day.  It should be
prescribed generically as amlodipine.  The besilate salt should not be prescribed as this is more expensive. 
 
GREEN       Amlodipine (as maleate/mesilate salt only) tablets 5mg, 10mg               
 
Lercanidipine or Lacidipine can be used as a  second line calcium channel blocker when amlodipine is not tolerated
(e.g. where patients develop significant ankle oedema).
 
GREEN      Lercanidipine tablets 10mg, 20mg 
GREEN      Lacidipine tablets 2mg, 4mg
 
Diltiazem is indicated for angina and hypertension. Prescribe modified-release diltiazem by brand name to avoid
confusion between different formulations.
Diltiazem (once daily preparations)
 
GREEN      Slozem® (Prescribe by brand name) capsules 120mg, 180mg, 240mg, 300mg   
 
Nimodipine is licensed only for subarachnoid haemorrhage.
RED           Nimodipine tablets 30mg  
RED           Nimodipine intravenous infusion 10mg/50mL
 
Verapamil is for angina, hypertension and arrhythmias, it reduces cardiac output, slows the heart rate and may 
precipitate heart failure.
 
GREEN      Verapamil    
                   tablets 40mg, 80mg, 120mg 
                   tablets m/r 120mg, 240mg
RED           Verapamil injection 5mg/2mL
 
Nicardipine IV for use on Critical Care Unit ELHT only, where beta-blockers not tolerated 
RED           Nicardipine IV 
 
Nifedipin MR - Hypertension during pregnancy and post-natal only
AMBER        Nifedipine MR tablets 10mg, 20mg
 

2.6.3 Other antianginal drugs

Nicorandil  
Nicorandil, a potassium channel activator with a nitrate component, has both arterial and venous dilating 
properties and is licensed for the prevention and long-term treatment of chronic stable angina pectoris. It is usually
prescribed in addition to isosorbide mononitrate if symptoms remain uncontrolled.  Patients already receiving 
MAXIMAL therapy with two antianginal medications (e.g. calcium channel blocker and nitrates) should be referred to a 
specialist for further assessment.
 
GREEN      Nicorandil tablets 10mg, 20mg
 
Ivabradine    
Chronic Stable Angina
 
          >     Ivabradine should only be initiated by specialists in the treatment of chronic stable angina. 
          >     Ivabradine has not demonstrated any increased benefits in terms of efficacy and safety over other available
                 treatments for angina, and is considerably more expensive.
          >     it is recommended for symptomatic treatment of chronic stable angina pectoris in patients with normal sinus
                 rhythm for whom heart rate control is desirable and for whom beta-blockers and calcium-channel blockers 
                 are inappropriate or not tolerated. Long-term protection against cardiovascular events, however, has not 
                 been demonstrated.
          >    Therefore patients already receiving MAXIMAL therapy with two antianginal medications (e.g. calcium channel
                 blocker and nitrates) should be referred to a specialist for further assessment.  
          >    There is no evidence that addition of a third drug improves symptom control.  If a third drug (e.g nicorandil) is
                 introduced while awaiting an outpatient appointment, its effects should be monitored and if it has no effect
                 it should be stopped.
AMBER     Ivabradine tablets 5mg, 7.5mg 
 
Chronic Heart Failure (NICE TA267)
          >     Ivabradine should only be initiated by specialists in the treatment of chronic heart failure
 
AMBER shared care    Ivabradine tablets 5mg, 7.5mg
 
Ivabradine prior to Cardiac CT if required to lower the heart rate
RED         Ivabradine for use prior to cardiac CT when the heart rate is raised
 
Ranolazine
Ranolazine should only be initiated by specialists in the treatment of chronic stable angina.
Ranolazine is recommended as add on therapy for symptomatic treatment of patients with stable angina whose
symptoms are inadequately controlled or intolerant  of first-line antianginal therapies, nitrates and/or nicorandil, 
and third line ivabradine.
 
          >     Ranolazine should only be initiated by specialists in the treatment of chronic stable angina
          >     Ranolazine is recommended as add on therapy for symptomatic treatment of patients with stable angina 
                 whose symptoms are inadequately controlled or intolerant of first-line antianginal therapies, nitrates and/or
                 Nicorandil, and third line Ivabradine and when there are no revascularisation options available to the patient
          >     Patients who experience a satisfactory response (reviewed by cardiologist after 3 months) may have their 
                 care transferred to primary care
AMBER     Ranolazine m/r tablets 375mg, 500mg, 750mg         
 
Management of Stable Angina Pathway, click here. 
 

2.6.4 Peripheral vasodilators and related drugs

Nifedipine may be useful for reducing the frequency and severity of vasospastic attacks in Raynaud’s syndrome.
Nifedipine is no longer recommended for the treatment of hypertension and angina.
GREEN      Nifedipine capsules 5mg, 10mg
 
Post-natal hypertension only 
AMBER    Nifedipine MR tablets
 
Sildenafil, as an option in severe primary or secondary Raynaud’s resistant to initial therapies (calcium channel
blockers). Unlicensed Use
RED           Sildenafil tablets 25mg   
 
NICE guidance for peripheral arterial disease (TAG 223)
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
i.e. generic prescribing only.

GREEN      Naftidrofuryl oxalate capsules 100mg


2.7.1 Inotropic sympathomimetics

Dobutamine and dopamine increase contractility of the heart with little effect on the rate, isoprenaline increases both the heart rate and contractility. Hospital use only.

RED           Dobutamine   
                   injection 250mg/20mL
RED           Dopamine         
                   injection 40mg/mL, 160mg/mL                                                                                                                                                     intravenous infusion 400mg in 250mL glucose 5%       
RED           Isoprenaline  
                   injection 100mcg/mL, 2mg/mL (unlicensed)         


2.7.2 Vasoconstrictor sympathomimetics

Increase blood pressure by constricting peripheral vessels. Used in emergency when other methods have failed. Hospital only.

RED           Noradrenaline acid tartrate (dilute before administration)    
                   sterile solution 8mg/4mL    
                   sterile solution 40mg/20mL  
                  (noradrenaline acid tartrate 2mg = noradrenaline base 1mg)
AMBER     Midodrinine (Bramox®) tablets 2.5mg (licensed product for postural hypotension)


2.7.3 Cardiopulmonary resuscitation

10mL of 1 in 10,000 adrenaline is given by central intravenous injection in cardiac arrest.

GREEN      Adrenaline injection 1 in 10,000

2.8.1 Parenteral anticoagulants

Unfractionated heparin
RED          Heparin sodium injection 1,000 units/mL
 
Intravenous heparin flushes are widely used to keep peripheral and indwelling lines patent. There are
risks in their use due to poor practice such as not being formally prescribing or part of a patient group
direction. Wrong products and strengths have been selected. There is no evidence that heparin flushes
have any advantage over normal saline for keeping peripheral lines patent so the latter should be used.
For more complex devices such as central venous or arterial catheters, the evidence is less clear. More 
specific policies may be required depending on the individual devices in use. All flush solutions should
only be administered following a prescription or patient group direction.
AMBER     Heparin sodium injection 10 units/mL (flush only)
 
Low molecular weight heparins (LMWH) and fondaparinux
There are a number of LMWHs licensed for both prevention and treatment of DVT/PE in the UK. The low 
molecular weight heparin (LMWH) for prophylaxis and treatment of venous thromboembolism used in
East Lancashire hospitals for surgical, medical and obstetric patients is tinzaparin.
 
Prophylaxis of venous thromboembolism
RED          Tinzaparin injection    
                  2500 units(0.25mL), 3500 units(0.35mL), 4500 units(0.45mL) – Pre-filled syringes
N.B: Care when prescribing/selecting strength of syringes - Different strengths available. 
 
Not for GP prescribing. Whole course supplied by hospital. Nursing staff may still administer with
written authorisation. Prescribers should ensure adequate supplies for patients, as they will not be able
to get additional supplies from their GP.
 
Treatment of pulmonary embolism and venous thrombosis.
AMBER    Tinzaparin  injection 
                  8,000 units(0.4mL),10,000 units(0.5mL), 12,000 units(0.6mL), 
                  14,000 units(0.7mL), 16,000 units(0.8mL), 18,000 units(0.9mL), - pre-filled syringes, and 
                  40,000 units in 2mL multidose vial
  N.B: Care when prescribing/selecting strength of syringes - Different strengths available.        
 
For initiation by or on the recommendation of a specialist, and continuation by a primary care
prescriber with the relevant competencies to do so. Nursing staff may still administer with written
authorisation.
For full guidance including Indications and monitoring, see..  
Best Practice Guidance: Use of Low Molecular Weight Heparins (LMWH) in Primary Care (Latest version 4)
 
Treatment of DVT and PE for hospitalised patients   
Prescriptions must include the indication when written on the inpatient prescription chart i.e Tinzaparin
treatment.  In addition the dose prescribed and the volume to be administered must  also be
clearly stated, and the patients weight should also be  stated on the prescription.
 
Thromboprophylaxis for medical & surgical inpatients 
EVERY hospitalised patient should have a documented, mandatory, VTE risk assessment on admission 
to identify any individual risk factors (in addition to any proposed surgery) that are known to increase 
the risk of developing venous thromboembolism. 
Prescriptions must include the indication when written on the inpatient prescription chart, i.e.
Tinzaparin prophylaxis.  In addition the dose prescribed and the volume to be administered must 
also be clearly stated.
N.B: Care when prescribing/selecting strength of syringes - Different strengths available. 
 
Monitoring Requirements for LMWHs (does not include fondaparinux)
       >     All patients who are to receive LMWH should have a platelet count checked on the day of
              starting  treatment.
       >     Patients exposed to LMWH (or heparin) in the last 100 days should have another platelet count
              check 24 hours after starting LMWH.
       >     If the platelet count falls by 50% or more or the patient develops new thrombosis or skin allergy
              at injection sites between day 4 and 14 consider a diagnosis of Heparin induced 
              thrombocytopenia and discuss with a haematologist urgently.
       >     There is NO need to monitor the anticoagulant activity of tinzaparin (eg INR or APTT)
 
Hirudins              
Bivalirudin is a hirudin analogue, thrombin inhibitor which  is licensed for acute coronary syndromes.
NICE guidance TA230 advises on its use in MI with persistent ST-segment elevation.
RED           Bivalirudin injection (Angiox®) 250mgs
 
Epoprostenol  
A prostacyclin that can be given during renal dialysis either alone or with heparin, and it is also licensed
for the treatment of primary pulmonary hypertension resistant to other treatments.  It is also used in
Raynaud’s syndrome (unlicensed). 
RED           Epoprostenol injection 500micrograms 
 
Fondaparinux   
A synthetic pentasaccharide that inhibits activated Factor X 
RED           Fondaparinux injection 2.5mg/0.5mL 
 
Treatment of acute coronary syndrome (ACS)


This includes SUSPECTED acute NSTEMI, Troponin Positive ACS and STEMI in conjunction with
thrombolysis.  Fondaparinux is administered as a fixed dose, 2.5mg/0.5mL once daily injection with no
requirement to weigh the patient. There is no need to monitor platelets.
 
Note: Fondaparinux provides a prophylactic level of anticoagulation and therefore is NOT suitable for
indications where a therapeutic level of anticoagulation is required e.g. mechanical prosthetic valve, AF
with high risk of cardiac thromboembolism, venous thromboembolism.  Use full dose tinzaparin in these
cases.
 
For the treatment of unstable angina and Non ST Elevation MI (except those patients receiving
emergency (<120minutes) PCI*:
Dose:                                         2.5mg ONCE DAILY
Mode of Administration:       Subcutaneous
 
N.B. This should be discontinued for patients with unstable angina if their Troponin comes back negative.
 
For the treatment of ST Elevation MI in patients receiving thrombolysis (fondaparinux should be given
in combination with either streptokinase or tenecteplase):     
Dose:                                         2.5mg ONCE DAILY
Mode of Administration - The first dose should be administered Intravenously and subsequent doses by 
                                               subcutaneous injection.    
 
Do not expel the air bubble prior to administration.

 *For intravenous administration the injection should be given through an intravenous bung into a
 cannula followed by a flush with 5mL Sodium Chloride 0.9%.
 

Length of treatment: For 48hrs after the last chest pain, up to 8 days or until hospital  discharge.               Patients undergoing exercise testing should be pain free and off fondaparinux for 24 hours – withhold fondaparinux on day of discharge.

Renal Impairment: Do not use if eGFR < 20 – Unfractionated Heparin should be used as per local protocols. No dose reduction is needed if eGFR > 20

Prescribing Guidance for Oral Anticoagulants

Click here to Access Guidelines and Leaflets

 2.8.2 Oral anticoagulants

AMBER       Warfarin tablets 1mg, 3mg, 5mg 
AMBER        Acenocoumarol (nicoumalone) tablets 1mg (Sinthrome®) 


Novel oral anticoagulants (NOACs)      
 

These drugs are relatively new to the market and the potential long‐term side effects are not yet fully known. Concerns also include that the optimal method of emergency reversal of the anticoagulant effects for all these agents is currently unclear in those patients who present with major bleeding. There are also concerns, highlighted by the MHRA regarding dabigatran use in renal insufficiency as exposure is substantially increased in these patients. The benefits of dabigatran and rivaroxaban over warfarin decline as INR control on warfarin increases. In patients where warfarin is well controlled (time in therapeutic range [TTR] >65%), the use of dabigatran or rivaroxaban may be less favourable.  On this basis, the use of these drugs should be implemented carefully and targeted to those patients that are likely to gain the most benefit from them i.e. patients poorly controlled on warfarin or those eligible for, but choose not to be anti coagulated with warfarin. 

An alert card is available in ELHE to clearly inform patients and healthcare professionals of key safety         information regarding the use of novel oral anticoagulants. All patients should be issued with this card.

Prevention of stroke and systemic embolism in atrial fibrillation 

GREEN         Dabigatran capsules 75mg, 110mg                       NICE guidance TA249 
GREEN         Rivaroxaban tablets 15mg, 20mg                            NICE guidance TA256


Prevention of stroke and systemic embolism in non-valvular atrial fibrillation
 

GREEN         Edoxaban tablets 15mg, 30mg, 60mg                    NICE  guidance TA355
GREEN          Apixaban tablets  2.5mg, 5mg                           NICE guidance TA275


Prevention of venous thromboembolism after total hip or knee replacement in adults

GREEN            Apixaban tablets  2.5mg                                            NICE guidance TA245
GREEN            Rivaroxaban tablets 10mg                                        NICE guidance TA170
GREEN             Dabigatran capsules 75mg, 110mg                         NICE guidance TA157


Pulmonary embolism and preventing recurrent venous thromboembolism

GREEN        Rivaroxaban tablets 15mg, 20mg                        NICE guidance TA287 

Deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism

GREEN         Rivaroxaban tablets 15mg, 20mg                             NICE  guidanceTA261

Deep vein thrombosis (DVT) and pulmonary embolism (PE) , and extended 
prevention of current DVT and PE in adults after initial treatment. 
Rivaroxaban 10mg is recommended for treatment of Deep Venous thrombosis and Pulmonary Embolism, and extended prevention of recurrent DVT and PE in adults
 
When extended prevention of recurrent DVT and PE is indicated (following completion of 
at least 6 months therapy for DVT or PE), the recommended dose is 10 mg once daily.
In patients in whom the risk of recurrent DVT or PE is considered high, such as those with 
complicated comorbidities, or who have developed recurrent DVT or PE on extended 
prevention with rivaroxaban 10 mg once daily, a dose of rivaroxaban 20 mg once daily
should be considered.
The duration of therapy and dose selection should be individualised after careful 
assessment of the treatment benefit against the risk of bleeding.

 

 

Time period

Dosing schedule

Total daily dose

Treatment and prevention of DVT and PE

 

Day 1 -21 

15mg twice daily

30mg

Day 22 onwards 

20mg once daily

20mg

Prevention of recurrent DVT and PE*

Following completion of at least 6 months therapy for DVT or PE

10mg once daily (20mg once daily if considered high risk of recurrent DVT/PE)

See guidance

10mg 

 
 * recommendation or initiation by a specilaist
AMBER        Rivaroxaban 10mg tablets

Deep vein thrombosis and/or pulmonary embolism - treatment and secondary prevention

GREEN         Dabigatran capsules 75mg, 110mg                            NICE  guidance TA327 
GREEN         Apixaban tablets 2.5mg, 5mg                                      NICE guidance TA341 


Treatment and prevention of recurrent Deep vein thrombosis or pulmonary embolism    
           

GREEN         Edoxaban tablets 15mg, 30mg, 60mg                  NICE  guidance TA354.

Prevention of adverse outcomes after acute management of acute coronary syndrome

GREEN          Rivaroxaban  tablets 2.5mg                                    NICE guidance TA335

Clinicians should consult the summary of product characteristics for further advice. Both products are likely to be used initially for patients requiring extended prophylaxis following discharge, or in patients with needle phobia. All supplies will be prescribed and dispensed by the hospital, and GPs should not be asked to pick up or continue prescribing for these agents. Neither agent requires any anti-coagulant monitoring.

2.8.3 Protamine sulphate

To counteract overdosage with heparin, but has anticoagulant effect if used in excess.

RED           Protamine sulphate injection 10mg/mL

GREEN      Aspirin tablets dispersible 75mg, 300mg     
GREEN      Clopidogrel tablets 75mg         
GREEN      Dipyridamole  tablets 25mg, 100mg  
                                             m/r capsules 200mg  
GREEN      Asasantin Retard® capsules (dipyridamole m/r 200mg plus aspirin 25mg)  
AMBER     Prasugrel f/c tablets 5mg, 10mg 
AMBER     *Ticagrelor tablets 60mg, 90mg NICE TA420           
AMBER     *Ticagrelor tablets 90mg    NICE TA236 
RED           Tirofiban 250microgram/ml, 50ml (12.5mg) injection 
 
* - See Prescribing Guidance below. 
    (GPs should be informed of patients being started on Ticagrelor by the trust using the "Ticagrelor GP Individual               Notification Form". To view sample form <click here>)

Ischaemic Stroke - NICE TA210

  • Clopidogrel is now recommended as the first line option, with no restriction on duration of treatment.
  • If treatment with clopidogrel is contraindicated or not tolerated, then aspirin may be used in combination with MR dipyridamole, with no restriction on duration of treatment.
  • If both clopidogrel and aspirin are contraindicated or not tolerated, then treat with MR dipyridamole alone with no restriction on duration of treatment§.

Transient Ischaemic Attack (TIA)

  • Long term clopidogrel is recommended for TIA, although it is not licensed for this indication. Ensure that the patient or carers are informed of off-licence use. 
  • Treatment with aspirin in combination with MR dipyridamole is recommended as an option where Clopidogrel is either contraindicated or not tolerated, but now there is no restriction on duration of treatment.
  • If treatment with aspirin or clopidogrel is contraindicated or not tolerated, then treat with MR dipyridamole alone with no restriction on duration of treatment§.

Myocardial Infarction (MI)

  • Aspirin remains the first line option.
  • If treatment with aspirin is contraindicated or not tolerated, then treat with GENERIC clopidogrel.
  • This guidance should be considered alongside existing NICE guidance on clopidogrel in combination with aspirin in people with unstable angina or NSTEMI (CG94); and those who have had an MI (CG48).

§ Although not discussed in this guidance, if treatment with clopidogrel and/or dipyridamole is contraindicated or not tolerated, treatment with aspirin alone would be a logical choice.

Aspirin                                                                                                                                                                       Ischaemic stroke in AF                                                                                                                                            Use aspirin for the following types of stroke: 

  • Acute ischaemic stroke (without primary intracerebral haemorrhage):                                                                      Give aspirin 300mg as soon as possible within 24 hours (see below).
 
  • Give orally if the person is not dysphagic
  • Give rectallly or by enteral tube if they have dysphagia
  • Continue aspririn 300mg for 2 weeks (or until discharged from hospital if sooner), then start long-term antiplatelets or anticoagulants as indicated.
  • Give a proton pump inhibitor with aspirin if dyspepsia with aspirin has previously been reported. 
 


Transient Ischaemic Attack                                                                                                                          

  • Start daily aspirin (300mg) immediately.
  • Introduce measures for secondary prevention once diagnosis is confirmed.
  • Assess risk of subsequent stroke

Immediate assessment

  • Use FAST (Face, Arm, Speech Test) in primary care to screen for diagnosis of stroke or TIA in people with sudden onset of neurological symptoms.
  • Admit anyone with suspected stroke to a specialist unit.

Treatment and management                                                                                                                                                   Dipyridamole is used as an adjunct to oral anticoagulation for prophylaxis of thromboembolism associated with prosthetic heart valves. The combination of modified-release (MR) dipyridamole and aspirin is recommended for people who have had a transient ischaemic attack (TIA). Thereafter, or if MR dipyridamole is not tolerated, preventative therapy should revert to standard care (including long-term treatment with low-dose aspirin).

Clopidogrel is used in acute coronary syndrome in combination with aspirin for up to 12 months, after which clopidogrel is stopped (and aspirin continued) unless otherwise advised by the consultant cardiologist.  It is also given following an ST-elevated myocardial infarction with aspirin for 28 days, after which clopidogrel is stopped and aspirin continued long term.

Clopidogrel alone is only recommended for people who are intolerant of low-dose aspirin and either have experienced an occlusive vascular event or have symptomatic peripheral arterial disease.  Aspirin intolerance is defined as either of the following: proven hypersensitivity to aspirin-containing medicines, OR a history of severe dyspepsia induced by low dose aspirin. 

Clopidogrel should not be used concomitantly with aspirin in the secondary prevention of stroke or TIA due to the increased bleeding risk.

Prasugrel NICE guidance TA317

Prasugrel 10 mg in combination with aspirin is recommended as an option within its marketing authorisation,  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.

The summary of product characteristics for prasugrel states that it should be started with a single 60 mg loading dose and then continued at 10 mg once a day. People taking prasugrel should also take 75 mg to 325 mg aspirin daily. Treatment for up to 12 months is recommended unless stopping prasugrel is clinically indicated.

According to the summary of product characteristics, the use of prasugrel in people 75 years or older is generally not recommended. However, if treatment is deemed necessary a reduced maintenance dose of 5 mg should be prescribed. For people who weigh less than 60 kg, the summary of product characteristics states that the 10 mg maintenance dose is not recommended and the 5 mg maintenance dose should be used. For people with unstable angina or NSTEMI, if coronary angiography is performed within 48 hours after admission, the summary of product characteristics states that the loading dose should only be given at the time of percutaneous coronary intervention.

Ticagrelor (Brilique®) in combination with aspirin is recommended as an option for preventing atherothrombotic events in people with acute coronary syndromes, covering STEMI (with PCI), NSTEMI and unstable angina  (NICE TA236).

Ticagrelor  (Brilique®) in combination with aspirin, is recommended as an option for preventing atherothrombotic events in adults who had a myocardial infarction and who are at high risk of a further event. (NICE TA420). Treatment should be stopped when clinically indicated or at a maximum of 3 years.

Thrombolytic treatment of myocardial infarction should be given as early as possible.

 2.10.2 Fibrinolytic drugs

RED           Alteplase injection 2mg

RED           Streptokinase injection 750,000 units per vial

RED           Tenecteplase 40mg and 50mg per vial

RED           Urokinase injection 10,000 units, 25,000 units, 100,000 units

RED           Tissue Plasminogen Activator (TPA) - for use by Opthalmology for submacular haemorrhage

Tranexamic acid inhibits plasminogen activation and fibrinolysis.

GREEN      Tranexamic Acid tablets 500mg
RED           Tranexamic Acid injection 100mg/mL


Other blood products – contact blood bank.

2.12 Lipid regulating drugs

Drug therapy should be combined with dietary control.               
Statins should be prescribed in line with NICE guidance CG181 July 2014 available here 
This guideline updates and replaces the previous NICE  guideline on lipid modification (CG67) . It offers evidence-based advice on the care and treatment of people at risk of cardiovascular disease and people who have had previous cardiovascular disease.        
A summary flow chart for cardiovascular risk assessment and the modification of blood lipids for
the primary and secondary prevention of cardiovascular disease in East Lancashire  is available here.  
 
Atorvastatin is now the first line agent – see lipid modification guidelines before prescribing
 
Statins 
First line 
GREEN      Generic Atorvastatin tablets 10mg, 20mg, 40mg, 80mg   
GREEN      Simvastatin tablets 20mg, 40mg     
GREEN      Pravastatin tablets 20mg, 40mg  
 
Simvastatin and Atorvastatin are associated with some significant drug-drug interactions.
The table below provides 
information and advice on managing these interactions.
 

 Interacting drug or food   Simvastatin
prescribing
 advice 
  
Atorvastatin
 prescribing
 advice
  
Potent CYP3A4 inhibitors,

including itraconazole, 

ketoconazole,

erythromycin, clarithromycin, 

telithromycin, and HIV protease inhibitors. 

All are contraindicated with simvastatin.  Avoid if possible: consider
temporary suspension of atorvastatin
if interacting drug is taken for short period.
Itraconazole: do not exceed
40mg atorvastatin daily.               
Clarithromycin: do not exceed
20mg atorvastatin daily.
HIV protease inhibitors: monitor
lipid levels to ensure lowest
necessary dose of atorvastatin is used. 
Ciclosporin*  Contraindicated with simvastatin. 
Do not exceed 10mg generic atorvastatin daily. 
 Danazol  Contra-indicated with simvastatin. 
No restriction in Summary of Product Characteristics. 
Verapamil, amiodarone.  Do not exceed
20mg simvastatin daily.  
Monitor lipid levels to ensure lowest necessary
dose of atorvastatin is used. 
Diltiazem  Do not exceed
20mg simvastatin daily.  
Monitor lipid levels to ensure lowest necessary
dose of atorvastatin is used.  
Amlodipine Do not exceed
20mg simvastatin daily
Monitor lipid levels to ensure lowest necessary
dose of generic atorvastatin is used.  
Grapefruit juice 
Avoid grapefruit juice. 
Limit intake of grapefruit juice to very small quantities (or avoid altogether).
Warfarin/courmarins† 
Monitor INR before starting
 treatment and regularly during
treatment, especially with dose
changes.
Monitor INR before starting treatment and
regularly during treatment, especially with dose changes.  
Fibrates† 
Increased risk of myopathy when
used with fibrates; do not exceed
10mg simvastatin daily (except with fenofibrate); gemfibrozil increases
 systemic exposure to simvastatin. 
Increased risk of myopathy when used with
 fibrates; gemfibrozil increases systemic exposure to atorvastatin. 
Ezetimibe† 
Additive risk of myopathy cannot be ruled out. 
Additive risk of myopathy cannot be ruled out. 

*Ciclosporin interacts with all statins and is contraindicated with rosuvastatin.                                                                                    †Warfarin/courmarins, fibrates and ezetimibe are important potential interactions to consider for all statins.

Intolerance of statins                                                                                                                                         

If a person is not able to tolerate a high‑intensity statin aim to treat with the maximum tolerated dose.                               Tell the person that any statin at any dose reduces CVD risk. If someone reports adverse effects when taking high‑intensity statins discuss the following possible strategies with them: 

  • stopping the statin and trying again when the symptoms have resolved to check if the symptoms are related to the statin
  • reducing the dose within the same intensity group.
  • changing the statin to a lower intensity group.
  • Seek specialist advice about options for treating people at high risk of CVD such as those with CKD, type 1 diabetes, type 2 diabetes or genetic dyslipidaemias, and those with CVD, who are intolerant to 3 different statins.
Fibrates in CVD -updated in line with NICE CG181

Do not routinely offer fibrates for the prevention of CVD to any of the following:

  • people who are being treated for primary prevention
  • people who are being treated for secondary prevention
  • people with CKD
  • people with type 1 diabetes
  • people with type 2 diabetes
GREEN      Fenofibrate (Supralip®) tablets 160mg


Ezetimibe     
People with primary hypercholesterolaemia should be considered for exetimibe treatment in line with Ezetimibe for
treating priimary heterozygous-familial and non-familial hypercholesterolaemia as per NICE TA358 (replaces NICE TAG132).
GREEN      Ezetimibe tablets 10mg  
 
Alirocumab (NICE TAG393) and Evolocumab (NICE TAG394) are recommended as options for treating primary
hypercholesterolaemia or mixed dyslipidaemia, 
RED         Alirocumab (Praluent ®) 
                 Solution for injection 75mg/mL, 150mg/ml                                                         (CCG commissioned) 
RED        Evolocumab (Repatha®)
                Solution for injection 140mg/1mL (pre filled pen)                                               (CCG commissioned)
 
Colesevelam  is not recommended as combination or monotherapy for familial hypercholesterolaemia.
BLACK     Colesevelam (Cholestagel®) 
Click here to access the New Medicines recommendation

Nicotinic acid group 
Do not offer nicotinic acid (niacin) for the prevention of CVD to any of the following: 
 
       >     people who are being treated for primary prevention
       >     people who are being treated for secondary prevention
       >     people with CKD
       >     people with type 1 diabetes
       >     people with type 2 diabetes

Omega-3-acid ethyl esters  
 
BLACK Omega-3-acid ethyl esters - Post Myocardial Infarction.

NHS England has identified this product as an item that should not be routinely prescribed in primary care. Available to purchase over the counter
Click here for the  Position Statement for Omega-3-acid ethyl ester prescribing in CVD 
 
BLACK Omega-3 fatty acid compounds for preventing CVD  
NHS England has identified this product as an item that should not be routinely prescribed in primary care. Available to purchase over the counter
Recommendations in this section update and replace recommendations 1.10.4.1 and 1.10.4.2 from Type 2 diabetes
(NICE clinical guideline 87). 

Omega-3-acid ethyl esters - Hypertriglcyeridaemia       
NHS England has identified this product as an item that should not be routinely prescribed in primary care. Available to purchase over the counter
 
BLACK    Omega-3-acid ethyl ester capsules 1g. 
 
Anion-exchange resins  
Do not offer a bile acid sequestrant (anion exchange resin) for the prevention of CVD to any of the following:
 
       >     people who are being treated for primary prevention
       >     people who are being treated for secondary prevention
       >     people with CKD
       >     people with type 1 diabetes
       >     people with type 2 diabetes
 
Combination therapy for preventing CVD 
Do not offer the combination of a bile acid sequestrant (anion exchange resin), fibrate, nicotinic acid or omega-3 fatty 
acid compound with a statin for the primary or secondary prevention of CVD. 

Used in sclerotherapy of varicose veins

RED           Sodium tetradecyl sulphate injection 3%