Data extracted : 24/11/2017
 Formulary Section 2: Cardiovascular system
02.01 Positive inotropic drugs
02.01.01 Cardiac glycosides
  • Digoxin controls the ventricular rate in patients with persistent or permanent atrial fibrillation, especially when it occurs with heart failure. It is also used in the treatment of supraventricular tachycardias and atrial flutter but not ventricular arrhythmias.
  • Digoxin should only be considered as monotherapy for permanent AF in predominantly sedentary patients who need treatment for rate control.
  • A loading dose may be given on initiation of therapy to achieve a rapid therapeutic effect; otherwise it will take about a week to obtain maximal effect. An oral loading dose is often satisfactory but for a more rapid onset it can be given by intravenous infusion. Even with intravenous administration, response may take many hours; persistence of tachycardia is therefore not an indication for exceeding the recommended dose.
  • In patients with heart failure who are in sinus rhythm a loading dose is not required, and a satisfactory plasma-digoxin concentration can be achieved over a period of about a week.
  • Intramuscular injection should be avoided as it is painful and absorption is variable.
  • Age and renal function are key determinants of the dosing regimen.
Link   NICE CG 180: Atrial Fibrillation
Link   Toxicology and Therapeutic Dose Monitoring
First Choice:
02.02 Diuretics

  • Diuretics help to reduce fluid overload in heart failure. Loop diuretics are preferred for acute exacerbations.  Thiazide-like diuretics are now recommended by NICE for the treatment of hypertension in newly diagnosed patients.  

  • Thiazide-like diuretics are fully effective only when renal function is normal or only minimally impaired and are contraindicated in severe impairment. Loop diuretics may be required in hypertensive patients with severe renal impairment.

  • Do not prescribe diuretics routinely later than early afternoon.

  • Thiazide-like and loop diuretics can cause serum-potassium levels to fall in some patients, particularly during the first few weeks of treatment. Hypokalaemia should be treated appropriately if it occurs. A potassium-sparing diuretic is generally more effective and convenient than potassium chloride supplements.  

  • Regular review of diuretic use is desirable to confirm continued need and to monitor adverse effects such as dehydration, which may cause renal impairment particularly in the elderly. Use of potassium supplements or potassium-sparing diuretics should be re-assessed regularly by measuring serum-potassium levels.
02.02.01 Thiazides and related diuretics
See section 2.2

  • The action of indapamide is progressive and the reduction in blood pressure may continue and not reach a maximum until several months after the start of therapy.

  • Indapamide is claimed to lower blood pressure with less metabolic disturbance than other diuretics particularly less aggravation of diabetes mellitus.

  • Metolazone and loop diuretics appear to have a synergistic effect when combined. Profound diuresis can occur so monitor patient carefully. Use intermittently based on achievement of a target weight. Reduce dose or stop treatment until target weight exceeded again.
  • Link   NICE CG 127: Hypertension
    First Choice:
    Indapamide 2.5mg 
    If a diuretic is to be initiated or changed. Existing patients should remain on bendroflumethiazide.
    NB Indapamide MR is not recommended as limited evidence of additional benefits and higher cost.

    Restricted Drug  Metolazone 
    Oedema resistant to large doses of loop diuretics alone.
    This product has been discontinued by the manufacturers but imported sources are now available. Local specialist opinion is to use bendroflumethiazide as an alternative in line with the recommendations of the British Society for Heart Failure.
    02.02.02 Loop diuretics
    • Furosemide (40-60mg) has a similar effect to bumetanide (1mg) for most clinical uses. Diuresis is complete within 6 hours of oral administration with both drugs therefore if necessary they can be given twice in one day without disturbing sleep.

    • Bioavailability of oral bumetanide is sometimes better than furosemide particularly in patients with right-sided congestive heart failure associated with liver/ splanchnic congestion.
    • The therapeutic effect of loop diuretics can be measured by monitoring the patient’s weight on a daily basis.
    • In acute heart failure, small doses of parenteral loop diuretics are valuable (onset of action approximately 5 minutes after IV injection).
    • Large doses of loop diuretics may be required in renal failure.
    Link   NICE CG 108: Chronic Heart Failure
    First Choice:
    IV Guide available through ’Injectable Medicines Guide’ link on front page of INsite.
    Second Choice:
    Restricted Drug  Torasemide 
    For consultant cardiologist signature only
    02.02.03 Potassium-sparing diuretics and aldosterone antagonists

    • Amiloride and spironolactone are weak diuretics if given alone, but their diuretic and antihypertensive effects are additive with those of loop and thiazide diuretics. They should be used in preference to potassium supplements if hypokalaemia is a problem with loop or thiazide diuretics alone.

    • Combinations should not be used unnecessarily and in practice are often not justified when treating hypertension, as the risk of hyponatraemia is greater than with one agent alone.

    • Amiloride and spironolactone may take 2-3 days to become fully effective.

    • Potassium-sparing diuretics are contra-indicated in renal failure; the elderly may insidiously develop hyperkalaemia due to deterioration in renal function.

    • Close monitoring required if prescribed together with other agents that raise serum potassium. These include potassium supplements, ACE inhibitors and angiotensin-II antagonists. Non-steroidal anti-inflammatory drugs (NSAIDs) and ciclosporin may also increase the risk of hyperkalaemia. Serum potassium should be monitored 3 monthly and within 7-14 days after a dose change.
    Link   NICE CG 108: Chronic Heart Failure
    First Choice:
    02.02.03 Aldosterone antagonists
    Link   NICE CG 108: Chronic Heart Failure
    Restricted Drug  Spironolactone 
    NICE recommends in patients with heart failure due to left ventricular systolic dysfunction who remain moderately to severely symptomatic despite optimal therapy of ACE inhibitors and β blocker. Specialist advice should be sought as monitoring required.
    Can also be used when an aldosterone antagonist is clearly indicated (e.g. primary hyperaldosteronism or treatment of oedema and/or ascites in hepatic cirrhosis).
    Restricted Drug  Eplerenone 
    Evidence supports the use in patients admitted to CCU following an MI with proven left ventricular failure in addition to other treatment. Second line as an alternative to spironolactone in patients who have chronic heart failure or hypertension and suffer from gynaecomastia.
    02.02.04 Potassium-sparing diuretics with other diuretics
    Combined loop or thiazide diuretic with a potassium-sparing agent should not be used indiscriminately. They are more expensive than diuretic alone and are more likely to cause hyponatraemia or other adverse reactions than a single agent.
    Co-amilofruse 5/40 
    Amiloride 5mg with furosemide 40mg
    Proprietary brands are more costly
    Co-amilozide 5/50 
    Amiloride 5mg with hydrochlorothiazide 50mg; (Moduretic)
    02.02.08 Diuretics with potassium

    Products that combine a diuretic with potassium chloride are not recommended because they often contain insufficient potassium (8-12mmol per tablet) to correct hypokalaemia.

    02.03 Anti-arrhythmic drugs

    • Management of arrhythmias other than atrial fibrillation should be under the care of a specialist. Advice can be found in the Cardiology Handbook.

    • For management of atrial fibrillation see the relevant sections on beta-blockers, digoxin and calcium channel blockers.

    • Restricted drugs should only be initiated on the advice of an appropriate hospital specialist.

    • Before starting anti-arrhythmic drugs, ensure accurate diagnosis, assessment of the severity of symptoms, the patient’s general condition, co-morbidities and consideration of the prognosis.

    • As a rule of thumb anti-arrhythmic drugs have the potential to be pro-arrhythmic!

    • Combinations of anti-arrhythmic agents are more likely to produce significant negative inotropic effects. Review periodically to determine whether treatment should be continued.
    02.03.01 Management of arrhythmias
    Link   Cardiology Handbook
    Link   Further Information: Antiarrhythmics Drugs For Specialist Initiation
    Link   NICE CG 180: Atrial Fibrillation
    02.04 Beta-adrenoceptor blocking drugs

    • NICE recommends beta-blockers as first line treatment in angina, rate control in persistent and permanent AF and also heart failure (alongside an ACE inhibitor). Beta blockers are also recommended post MI in clinically stable patients.
    • Beta blockers are now only recommended for the treatment of resistant hypertension.
    • Bisoprolol and carvedilol are beta blockers licensed for use in heart failure. They may also be preferred in post MI patients with LVSD.
    • Existing co-morbidities need to be taken into account when prescribing beta blockers especially in patients with poorly controlled diabetes, reversible airways disease and unstable heart failure. Cardio-selective beta blockers such as atenolol and bisoprolol may be preferable when there are no other alternatives.
    • Introduce beta blockers slowly. Gradually reduce the dose if beta-blockers are to be stopped as sudden withdrawal may cause an exacerbation of angina and rebound worsening of myocardial ischaemia.
    • For specialist use of beta-blockers to treat arrhythmias see section 2.3
    Link   NICE CG 108: Chronic heart failure
    Link   NICE CG 126: Stable Angina
    Link   NICE CG 127: Hypertension
    Link   NICE CG 172: MI secondary prevention
    Link   NICE CG 180: Atrial fibrillation
    Link   UHL Guidelines: Hypertensive emergencies
    First Choice:
    Bisoprolol Fumarate 
    Restricted Drug  Carvedilol 
    For use in heart failure only. Initiation and titration should be by a health care professional with experience in managing heart failure.
    Restricted Drug  Atenolol 
    Intravenous and liquid preparations available

    Existing patients can continue receiving tablets
    UHL also use in post natal patients if not breast feeding
    Restricted Drug  Propranolol Hydrochloride 
    Less cardioselective and shorter acting than atenolol. Drug of choice for thyrotoxic crisis and portal hypertension. Dose requirements may differ considerably between individuals because of variable first-pass hepatic metabolism.
    02.05 Drugs affecting the renin-angiotensin system and some other antihypertensive drugs
    02.05.01 Vasodilator antihypertensive drugs

    • Seek specialist advice on the management of hypertensive emergencies

    • In treatment of hypertensive urgencies, diastolic pressure should ideally be lowered to 100-110mmHg over the first 24 hours of treatment with oral BP-lowering treatment. Avoid a sudden dramatic fall in blood pressure, particularly in chronic hypertensives and the elderly as it can result in reduced cerebral perfusion, deterioration in renal function and myocardial ischaemia.  Aim to lower blood pressure over several days with oral drugs and close monitoring.

    • Hypertensive encephalopathy and left ventricular failure are hypertensive emergencies and as such require more rapid reduction in blood pressure with intravenous BP-lowering treatment.

    Link   NHSE Commissioning Policy: Targeted Therapies for Pulmonary Hypertension Functional Class II
    Link   NHSE Commissioning Policy: Targeted therapies for the treatment of pulmonary hypertension in adults
    Link   UHL Guidelines: Hypertensive emergencies
    Link   UHL Guidelines: Management of severe pre-eclampsia / eclampsia
    Restricted Drug  Sodium Nitroprusside 
    Recommended choice for hypertensive crisis
    Starts to act within a few minutes. Blood pressure can be readily controlled by adjusting the infusion rate. It can be used in dissecting aortic aneurysm in combination with a beta-blocker to prevent an increase in heart rate.
    Restricted Drug  Labetalol 
    After bolus injection, the maximum effect usually occurs within five minutes and the effective duration of action is usually about six hours but may be as long as eighteen hours.
    Alternative choice to sodium nitroprusside for hypertensive crisis.
    Labetalol can also be used during pregnancy (3rd trimester) for management of severe pre-eclampsia/ eclampsia.
    Restricted Drug  Hydralazine Hydrochloride 
    Useful for hypertensive emergencies in pregnancy. Second line choice after labetalol for pre-eclampsia /eclampsia. Acts about 20 minutes after IV injection (slightly longer if given IM).
    02.05.02 Centrally acting antihypertensive drugs
    Restricted Drug  Moxonidine 
    For initiation by hypertension clinic only.
    02.05.03 Adrenergic neurone blocking drugs
    02.05.04 Alpha-adrenoceptor blocking drugs

    • Lower blood pressure by arteriolar and venous dilatation.

    • Not recommended by NICE in the treatment of hypertension until step 4.

    • May improve urine flow in men with benign prostatic hyperplasia and therefore may be an additional benefit in such patients.

    • Alpha-blockers can cause postural hypotension. Gradual upward titration of the dose will minimise the risk of syncope when therapy is initiated.

    First Choice:
    Standard release preparation.
    Modified release preparations are more expensive and offer no clinical advantage over standard release preparations.
    02.05.05 Drugs affecting the renin-angiotensin system Angiotensin-converting enzyme inhibitors (ACE inhibitors)

    (ACE) inhibitors are recommended by NICE for the following:

    • Step 1 for the treatment of hypertension in patients under 55 years  (other than black patients of African or Caribbean family origin of any age).

    • ACE inhibitors are recommended at step 2 for treatment of hypertension for those over 55 years. Losartan should be used in preference to an ACE inhibitor in black patients of African or Caribbean family origin of any age at step 2.

    • All patients with heart failure due to LVSD should be considered for treatment with an ACE inhibitor. The dose should be titrated to the recommended ’target’ or maximum tolerated.

    • Type 2 diabetic patients with renal nephropathy.

    • Secondary prevention after acute myocardial infarction.

    • ARBs are useful alternatives in patients in whom ACE inhibitors are contraindicated or not tolerated.
    Link   NICE CG 108: Chronic heart failure
    Link   NICE CG 127: Hypertension
    Link   NICE CG 172: MI secondary prevention
    Link   NICE CG 87: Type 2 Diabetes - newer agents (a partial update of CG66)
    First Choice:
    Hypertension and heart failure.
    In heart failure, target dose is 20mg daily.
    Second Choice:
    Hypertension and heart failure.
    In heart failure, target dose is 10mg daily.
    Restricted Drug  Perindopril erbumine 
    Initiation restricted on the advice of a senior cardiologist to patients where
    hypotension is a significant issue with 1st line choices or in hypotensive patients as a first line choice.

    Restricted Drug  Lisinopril + Hydrochlorothiazide   (Zestoretic®)
    On advice of the hypertension clinic only Angiotensin-II receptor antagonists
    • Do not routinely prescribe ARBs except as an alternative to an ACE inhibitor where there is a contraindication, intolerance or allergy.
    • NICE Guidelines for Hypertension recommend losartan at step 2, in preference to an ACE inhibitor in black patients of African or Caribbean family origin of any age.
    • All local organisations are monitored to ensure that this happens using the National ’Better Care Value Indicators’
    Link   NICE CG 108: Chronic heart failure
    Link   NICE CG 127: Hypertension
    Link   NICE CG 172: MI - secondary prevention
    Link   NICE CG 87: Type 2 Diabetes - newer agents (a partial update of CG66)
    First Choice:
    Losartan Potasium 
    Hypertension and heart failure.
    Also licensed for diabetic nephropathy in type 2 diabetes.

    Second Choice:
    Hypertension and heart failure but is more expensive than losartan.
    Restricted Drug  Valsartan 
    May be used for post-MI heart failure if intolerant of an ACE inhibitor. Use is not recommended for other indications as it is more expensive than recommended choices.
    Restricted Drug  Sacubitril Valsartan  (Entresto® )
    For use by Heart Failure Clinic in line with NICE TA 388 only. If initiated by Heart Failure Clinic, GPs may continue prescribing under shared care Renin inhibitors
    Restricted Drug  Aliskiren 
    Aliskiren is available for treatment of hypertension if initiated by appropriate specialists at UHL. GPs may continue prescribing under shared care.

    02.06 Nitrates, calcium-channel blockers, and potassium-channel activators
    02.06.01 Nitrates

    • Nitrates are the mainstay of treatment for acute angina. They can also be used prophylactically if necessary e.g. before exertion. 

    • NICE recommends that nitrates are offered as a 3rd line option for prophylaxis of stable angina.   


    First Choice:
    Glyceryl Trinitrate Spray (GTN) 
    For acute angina.
    Spray acts within about 2 minutes and is effective for up to 30 minutes.
    First Choice:
    Isosorbide Mononitrate 
    Prophylaxis of angina.
    Give the standard-release version twice a day with the last dose of the day in the early afternoon to allow an adequate nitrate-free period and prevent development of tolerance. Modified release forms should not be used routinely as they are more expensive and tolerance is more likely to develop.
    02.06.02 Calcium-channel blockers

    • Dihydropyridine calcium-channel blockers are recommended by NICE as first line treatment of hypertension in black patients of African or Caribbean origin of any age and for all other patients aged 55 or older. 

    • Recommended by NICE as a first line treatment option of stable angina (diltiazem).

    • Rate controlling calcium channel blockers are recommended by NICE as a first line option for rate control in persistent and permanent AF.

    • Calcium-channel blockers do not reduce the risk of myocardial infarction in unstable angina.

    • The pharmacological action of calcium-channel blockers differ significantly. Co-morbidities and other medication need to be taken into account when prescribing.

    • Sudden withdrawal may exacerbate angina.
    Link   NICE CG 126: Stable Angina
    Link   NICE CG 127: Hypertension
    Link   NICE CG 180: Atrial fibrillation
    First Choice:
    Greater effect on vascular smooth muscle than in the heart and tend not to cause clinical deterioration in heart failure.
    First Choice:
    Diltiazem Hydrochloride 
    Avoid in heart failure because it may further depress cardiac function and cause clinically significant deterioration. Monitor heart rate if co-prescribed with a β-blocker. Prescribe longer acting formulations by brand. Use Angitil SR for twice daily dosing and Viazem XL for once daily.
    Restricted Drug  Lacidipine 
    Occasionally used by the hypertension clinic.
    Restricted Drug  Nifedipine  
    Once or twice daily preparations
    For use in Obstetrics, Nephrology, Raynauld’s syndrome. Also available for emergency treatment of hypertension in acute medical and cardiology settings
    02.06.03 Other anitanginal drugs
    Link   NICE CG 126: Stable Angina
    Restricted Drug  Ivabradine 
    For patients with angina who cannot tolerate beta blockers, calcium channel blockers or nitrates.
    Amber traffic light status for chronic heart failure in line with NICE TA267

    Date of entry of decision to Formulary: February 2013
    Restricted Drug  Nicorandil 
    A potassium channel activator used for the prophylaxis of angina where calcium channel blockers, beta blockers or nitrates are either contraindicated, not tolerated or if symptoms are not adequately controlled.
    Restricted Drug  Ranolazine 
    For use in line with NICE CG 126. Ranolazine may be initiated in primary care but use should be audited. Second appointment recommended to assess effect and titrate dose if necessary one month after initiation.
    02.06.04 Peripheral vasodilators and related drugs
    Most peripheral vasodilators are considered less suitable for prescribing by the BNF and are not recommended for prescribing in the Leicestershire community.  NICE TA223 recommends naftidrofuryl as an option for treatment.  This is not routinely stocked at UHL but is available on request.
    Link   NICE CG 147: Lower limb peripheral arterial disease: guidance
    Link   NICE TA 223: Peripheral arterial disease
    02.07 Sympathomimetics
    02.07.01 Inotropic sympathomimetics

    • For prescribing in hospital only.

    • Inotropic sympathomimetics increase cardiac contractility, but they are haemodynamically different. In addition, the main effects of dopamine depend on the dose administered. In low doses, cardiac stimulation and renal vascular dilation occur and in larger doses vasoconstriction occurs. See Cardiology Handbook 2015 for further information.

    • Increased heart rate and arrhythmias may occur but dobutamine may be slightly less chronotropic and arrhythmogenic than dopamine used at a higher dose.
    First Choice:
    Caution in severe hypotension.
    IV Guide available through ’Injectable Medicines Guide’ link on front page of INsite.
    Second Choice:
    Dopamine Hydrochloride 
    Contra-indicated in patients with tachyarrhythmias or phaeochromocytoma. IV Guide available through ’Injectable Medicines Guide’ link on front page of INsite.
    02.08 Anticoagulants and protamine
    Link   NICE CG 144: Venous thromboembolic diseases
    02.08.01 Parenteral anticoagulants

    • Unfractionated heparin (UFH) is also known as standard heparin. It is useful for the treatment of very short term anticoagulation or in patients where there is a high risk of bleeding and in renal impairment as it has a short duration of action and can also be fully reversed by protamine.

    • Subcutaneous low molecular weight heparins LMWH such as dalteparin are preferred for routine use.

    • Flushing intravenous catheters: Sodium chloride 0.9% is recommended to maintain the patency of standard IV lines although heparinised solutions are used for indwelling central lines.
    Link   NICE CG 92: Venous thromboembolism: reducing the risk
    Link   NPSA alert: Risks with Intravenous Heparin Flush Solutions
    Link   UHL Guidelines: Skin Tunnelled Catheter Procedure Manual
    First Choice:
    Heparin Sodium 
    IV full anticoagulation. Prophylaxis
    First Choice:
    Heparin Sodium 
    For flushing of lines
    Restricted Drug  Argatroban 
    Specialist renal use only.
    For treatment of HIT or suspected HIT in patients with renal impairment (CrCl <20 ml/min) For CrCl 20-50 ml/min, discuss with an haemostasis and thrombosis clinician
    02.08.01 Low molecular weight heparins

    • Low molecular weight heparins (LMWH) are the usual first choice for anticoagulation as they are easier to administer than unfractionated heparin (UFH) and do not require APTT monitoring.

    • For prevention of VTE, all in-patients and day case surgery patients should be risk assessed using the appropriate risk assessment tool and prescribed dalteparin 5000units daily if indicated and if there are no contraindications. In patients with creatinine clearance<30ml/min reduce the dose to 2,500units daily.

    • Therapeutic doses should be calculated according to patient weight and renal function. The prescriber should document the weight of the patient on the prescription.
    Link   NICE CG 92: Venous thromboembolism: reducing the risk
    Link   NPSA alert: Reducing treatment errors with LMWH
    Link   RCOG Guidance: Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium
    Link   UHL Guidance: Dalteparin Administration Guide
    First Choice:
    Dalteparin Sodium  (Fragmin®)
    Second Choice:
    Enoxaparin Sodium  (Clexane®)
    For acute coronary syndromes.
    02.08.02 Oral anticoagulants

    • Warfarin is a competitive antagonist of vitamin K (phytomenadione), involved in the production of clotting factors. Its anticoagulant effect takes 36-48 hours to develop fully and is monitored using the international normalised ratio (INR). For treatment of VTE, heparin should continue for at least 5 days following warfarin initiation and not stopped until the INR has been in the therapeutic range for two consecutive tests.

    • Guidance on indications and target INRs are listed in the UHL Guidelines on Initiation of Oral Anticoagulation

    • The Anticoagulation (Warfarin) Induction Pack should be used for all new patients starting therapy with warfarin.

    • The Anticoagulation Initiation Pack for Oral Direct Factor Xa Inhibitors and Thrombin Inhibitors should be used for all new patients starting on either rivaroxaban, apixaban or dabigatran. 

    • The recommended inpatient dosing time for warfarin is 2pm and the INR should be measured between 8-10am the following morning.

    • Both vitamin K (phytomenadione) and prothrombin complex concentrate product are used for the emergency reversal of warfarin. Administration must not be delayed.

    • There is currently no product available for the emergency reversal of apixaban, dabigatran or rivaroxaban

    • All patients discharged from hospital on anticoagulants should be referred to the UHL anticoagulant clinic for counselling.

    • Rivaroxaban for preventing adverse outcomes after acute management of acute coronary syndrome is available for use by consultant cardiologists on request. Use only in line with NICE TA 335.  Decision added June 16. Traffic light status is red for this indication.
    Link   Initiation Pack for Oral Direct Factor Xa Inhibitors and Thrombin Inhibitors in AF for Primary Care
    Link   MHRA Advice: Dabigatran (Pradaxa): contraindicated in patients with prosthetic heart valves.
    Link   NICE CG 172: MI secondary prevention
    Link   NICE CG 180: Atrial Fibrillation
    Link   NICE TA 157:Dabigatran etexilate for the prevention of venous thromboembolism after hip or knee replacement surgery in adults
    Link   NICE TA 170: Rivaroxaban for the prevention of venous thromboembolism after total hip or total knee replacement in adults
    Link   NICE TA 249: Dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation
    Link   NICE TA 256: Rivaroxaban for the prevention of stroke and systemic embolism in people with atrial fibrillation
    Link   NICE TA 261: Venous thromboembolism (treatment and long term secondary prevention) - rivaroxaban
    Link   NICE TA 275: Apixaban for preventing stroke and systemic embolism in people with nonvalvular atrial fibrillation
    Link   NICE TA 287: Rivaroxaban in Pulmonary Embolism
    Link   Safety: Make Medicines Safe - Vitamin K
    Link   UHL Guidelines: Dabigatran Bleeding Protocol
    Link   UHL Guidelines: Initiation of Oral anticoagulation
    Link   UHL Guidelines: Management of Bleeding Complications in patients on Apixaban & Rivaroxaban
    Link   UHL Guidelines: Management of Bleeding Complications in patients on Dabigatran
    Link   UHL Guidelines: Management of warfarin overdose
    Link   UHL Initiation Pack for Oral Direct Factor Xa Inhibitors and Thrombin Inhibitors in AF for non specialists.
    Link   UHL Prescriber Checklist for Oral Direct Factor Xa Inhibitors and Thrombin Inhibitors
    Within UHL give 1mg tablets to all patients initiated on warfarin.
    Patients already established on warfarin should receive the strengths of tablets they are used to.
    For Atrial Fibrillation (AF) use in line with the Leicestershire Algorithms.

    Date of entry of decision to Formulary: August 2012
    For Atrial Fibrillation (AF) use inline with the Leicestershire Algorithms.

    Date of entry of decision to Formulary: May 2013
    Dabigatran etexilate 
    For Atrial Fibrillation (AF) use inline with the Leicestershire Algorithms.
    For Atrial Fibrillation (AF) use inline with the Leicestershire Algorithms.

    Date of entry of decision to formulary: November 2015
    Restricted Drug  Rivaroxaban 
    For DVT and PE use in line with SCA. Patients should be referred to the anticoagulant clinic for counselling.

    Date of entry of decision to Formulary:
    PE - September 2013
    DVT - October 2012
    Restricted Drug  Apixaban 
    For DVT and /or PE use in line with NICE TA 341 only

    Date of entry of decision to formulary: September 2015
    Restricted Drug  Dabigatran etexilate  
    Available on request for DVT and PE.
    Use in line with NICE TA 327

    Date decision added to Formulary: February 2015
    Restricted Drug  Edoxaban 
    Available on request for treating and preventing DVT and PE in line with NICE: TA 354

    Date of entry of decision to formulary: October 2015
    Restricted Drug  Acenocoumarol 
    Red traffic light status for new patients but existing patients can continue to be supplied by primary care
    Restricted Drug  Fondaparinux Sodium 
    For HIT
    02.08.03 Protamine sulphate
    Protamine injection can be given to reverse the effect of heparin if an immediate effect is required.
    Link   UHL Guidance: Unfractionated Heparin (UFH) Adult Infusion
    Protamine sulphate 
    IV Monograph available through ’Injectable Medicines Guide’ link on front page of INsite.
    02.09 Antiplatelet drugs

    • Use of low dose aspirin for the primary prevention of heart attacks and strokes in people without cardiovascular disease including diabetic patients is no longer recommended as the increased risk of bleeding outweighs any vascular benefits.

    • Prescribing of antiplatelets for secondary prevention should be line with appropriate UHL or LMSG Guidelines.

    • Patients with mild to moderate dyspeptic symptoms taking aspirin should be prescribed a PPI or H2 antagonist before switching to clopidogrel (which may also cause gastro-intestinal adverse effects).

    • The MHRA has updated its advice on the interaction between PPI’s and clopidogrel. It now recommends that use of either omeprazole or esomeprazole with clopidogrel should be discouraged. This does not include lansoprazole.
    Link   NICE CG 172: MI - secondary prevention
    Link   NICE CG 180: Atrial fibrillation
    Link   NICE CG 94: Unstable angina and NSTEMI
    Link   NICE TA 152: Drug – eluting stents for the treatment of coronary artery disease
    Link   NICE TA 210: Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events
    Link   UHL Guidelines: Acute Stroke and TIA Management
    Link   UHL Guidelines: Cardiology Handbook
    In line with guidance from the Royal College of Physicians’, LMSG recommends that clopidogrel at a dose of 75mg daily (following initial 300mg loading dose) is used for stroke and TIA patients in sinus rhythm. See link below

    Restricted Drug  Dipyridamole 
    Restricted Drug  Prasugrel 
    For ACS In line with Shared Care Agreement (SCA)and UHL guidance

    Date decision added to Formulary: September 2014
    Restricted Drug  Ticagrelor 
    For treatment ACS In line with NICE TA236 and UHL guidance.
    For prevention of atherothrombotic events in line with NICE TA420.
    On consultant cardiologist authorisation only.
    02.10 Myocardial infarction and fibrinolysis
    02.10.01 Management of myocardial infarction

    • Percutaneous Coronary Intervention (PCCI) is first line treatment of ST-segment elevation myocardial infarction (STEMI). Thrombolysis is now rarely used at UHL.

    • Further information on the management of STEMI can be found in the UHL Cardiology Handbook and UHL- ED Management of STEMI Guidelines
    Link   NICE TA 52: MI - thrombolysis
    Link   UHL Cardiology Handbook
    Link   UHL Guidelines: LRI ED Management of STEMI
    02.10.02 Fibrinolytic drugs
    • Rapid treatment with thrombolytics is essential and need to be administered within time frames specified in local and national guidelines.

    • Laboratory monitoring is necessary, initially to exclude coagulation defects and subsequently to ensure that fibrinolysis is occurring.
    • Tranexamic acid should be available to use as an antidote if necessary.
    Link   NICE CG 172: MI - secondary prevention
    Link   NICE CG 68: Stroke: Diagnosis and acute management of stroke and T.I.A.
    Link   NICE TA 52: MI - thrombolysis
    Link   UHL Guidelines: Cardiology Handbook
    Link   UHL Guidelines: LRI ED Management of STEMI
    Link   UHL Guidelines: Thrombolytic Therapy in Pulmonary Embolism
    First Choice:
    Replaces Reteplase which has been discontinued

    Treatment of STEMI
    Restricted Drug  Alteplase 
    For use in selected specialist situations including stroke and massive PE.

    Date of entry of decision to Formulary: September 2012
    02.11 Antifibrinolytic drugs and haemostatics
    First Choice:
    Tranexamic Acid 
    Inhibits activation of plasminogen. Used to prevent bleeding or treat bleeding associated with excessive fibrinolysis. Intravenous use as an antidote to thrombolytics is restricted to hospital use.
    02.11 Blood-related products
    Blood products are supplied by blood bank and NOT pharmacy.

    High cost products excluded to tariff are commissioned by NHSE in line with BCSH guidelines
    Restricted Drug  NovoSeven® 
    Available only with the agreement of the Haematology Specialist Registrar or Haematology Consultant.
    Restricted Drug  Prothrombin Complex Concentrate 
    Available only with the agreement of the Haematology Specialist Registrar or Haematology Consultant.
    Restricted Drug  Antithrombin III (Kybemin®)  
    Available only with the agreement of the Haematology Specialist Registrar or Haematology Consultant.

    Restricted Drug  Idarucizumab   (Praxbind)
    For reversal of dabigatran related bleeding only. Not suitable for other DOAC related bleeds.

    Idarucizumab is available in ED
    02.12 Lipid-regulating drugs

    Simvastatin 40mg daily is the usual first line choice for lipid lowering for the majority of patients for primary and secondary prevention except in ACS, renal transplant patients and patients on concurrent medications where there is a significant interaction and a lower dose of simvastatin or atorvastain is appropriate. 

    • Leicestershire Lipid Modification Guidance summarises the recommendations of NICE CG 66 and 67.

    • Review statin choice after six months in patients treated for ACS and follow secondary prevention pathway.

    • For patients aged 75 or older the decision to treat should be made on an individual basis.

    • Refer all patients with total serum cholesterol >10.0mmol/L or fasting serum triglycerides >10 to an appropriate specialist clinic.

    • Treatment of familial hypercholesterolaemia should be in line with NICE CG 71.
      For further advice contact: 
      Lipid Clinic on (0116) 287 1471 ext. 3029
      Chemical Pathology on (0116) 258 6550
    Link   Interactive Risk Calculator: QRISK2
    Link   Leicestershire Guidance: Lipid Modification
    Link   Leicestershire Statement on the use of Statins in Terminal Care
    Link   MHRA Advice: Simvastatin: updated advice on drug interactions - updated contraindications.
    Link   NICE CG 181: Lipid Modification.
    Link   NICE CG 182: Chronic Kidney disease
    Link   NICE CG 71: Familial Hypercholesterolaemia
    Link   NICE NG 28: Type 2 diabetes in adults: management (Updates and replaces NICE guidelines CG 87, CG 66, TA 248 and TA 203
    Restricted Drug  Evolocumab   (Repatha®)
    For use by the lipid clinic only.
    Approved in line with NICE TA 394 (added September 2016) for treating primary non-familial hypercholesterolaemia and mixed dyslipidaemia and primary heterozygous familial hypercholesterolaemia

    Use for homozygous familial hypercholesterolaemia is commissioned by NHS England only through established apheresis centres. UHL is not one of these so any request for treatment in this circumstance would need to be referred to one of the following: Central Manchester University Hospitals NHS Foundation Trust; Queen Elizabeth Hospital Birmingham; Royal Brompton and Harefield NHS Foundation Trust; Imperial College NHS Trust and University Hospitals Bristol NHS Foundation Trust.

    Restricted Drug  Alirocumab   (Praluent®)
    For use by the lipid clinic only.
    Approved in line with NICE TA 393 (added September 2016)for treating primary non-familial hypercholesterolaemia and mixed dyslipidaemia and primary heterozygous familial hypercholesterolaemia
    02.12 Bile acid sequestrants
    Colestyramine / Colestid are cholesterol binding resins which bind bile acids in the gut as well as ingested cholesterol to reduce LDL cholesterol. Other drugs should be taken at least 1 hour before or 4–6 hours after colestyramine to reduce possible interference with absorption.
    02.12 Ezetimibe
    Ezetimibe inhibits the intestinal absorption of dietary and biliary cholesterol.  It has a limited place in therapy and should be prescribed only in line with Leicestershire Lipid Modification Guidance and NICE TA 385
    Link   NICE TA 385: Ezetimibe for treating primary heterozygous-familial and non-familial hypercholesterolaemia (replaced TA 132)
    02.12 Fibrates
    Fibrates reduce very low density lipoprotein (VLDL), LDL cholesterol and triglycerides in addition to raising HDL. The MHRA has advised “Fibrates should only be used as first-line therapy in patients with isolated severe hypertriglyceridaemia (specialist use). In patients with mixed hyperlipidaemia, fibrates may be used only when a statin or other effective treatments are contraindicated or not tolerated.” The combination of statin with fibrate increases the risk of side effects and toxicity including serious muscle toxicity; therefore use with caution and monitor closely.
    Restricted Drug  Fenofibrate 
    200mg od dose preferred over other standard regimens as similar efficacy but lower acquisition cost.
    Restricted Drug  Bezafibrate 
    More expensive than fenofibrate.
    02.12 Statins
  • All statins act by inhibiting an enzyme involved in cholesterol synthesis. They reduce LDL with little effect on high density lipoprotein (HDL) cholesterol or triglycerides.

  • Simvastatin (alternative pravastatin) is the first line choice for lipid lowering for the majority of patients.
  • In practice, simvastatin 80mg and atorvastatin 80mg are less well tolerated compared to a 40mg dose and give minimal additional cholesterol-lowering efficacy.
  • First Choice:
    20mg once daily 1st choice in line with LMSG guidance
    Restricted Drug  Fluvastatin 
    For use in renal transplant patients only.
    Restricted Drug  Pravastatin Sodium 
    Low intensity statin with alternative metabolic pathway for use in patients who do not tolerate simvastatin.
    Also suitable for patients in allogeneic stem cell transplants due to lower level of interactions.
    Restricted Drug  Rosuvastatin 
    High intensity statin with alternative metabolic pathway for use in patients with ACS who do not tolerate atorvastatin.
    02.12 Nicotinic acid group
    Nicotinic acid reduces very low density lipoprotein (VLDL) and triglycerides and increases HDL. It is now only available as a combined product Tredaptive (nicotinic acid and laropiprant). Laropiprant suppresses the flushing associated with administration of nicotinic acid.
    Link   MHRA Advice: Tredaptive (combined niacin-laropiprant): no longer for prescribing as preliminary HPS2-THRIVE trial failed to show benefit outweighs risks.
    02.12 Omega-3 fatty acid compounds
    Restricted Drug  Omacor 
    Omacor is classified as Simple AMBER on the Leicestershire traffic light system for use in hypertriglyceridemia. Initiation is limited to the lipid clinic at UHL but may then be continued in primary care. It is classified as BLACK for other uses