Heart Failure Nurse Specialist: Pharmacological Management of Heart Failure

Transcription

1 Heart Failure Nurse Specialist: Pharmacological Management of Heart Failure Author(s) & Designation Lead Clinician if appropriate In consultation with To be read in association with Ratified by Linda Edmunds, SOPT Consultant Nurse Tracey Worland, Clinical and Operational Lead Heart Failure Team Tanshin Lim, Community Services Pharmacist Mary Lewis, Director of Nursing and Therapies Heart Failure Specialist Nurses British National Formulary (most up to date version or NICE guidelines for management of Chronic Heart Failure CG108 (2010) European society cardiology guidance on treatment of chronic heart failure (2016) The Scottish Intercollegiate Guidelines Network Management of chronic heart failure (SIGN 2016) Guideline 147 Medicines Management Group Re-issue/Ratification date October 2016 Version 3 Review date October 2018 This policy supports compliance with the CQC 5 Domains: Safe, Caring, Effective, Responsive, Well Led NHSLA Risk Management Standard(s): If you require this document in a different format, please contact the Quality and Governance team on

2 Contents 1. Introduction 3 2. Purpose / Objective of the Document 3 3. Responsibilities 3 4. Process 3 5. Training Requirements Monitoring of Compliance with the Policy including frequency References Associated Documents Appendices 44 Appendix 1 Checklist with initiating Sacubitril / Valsartan 45 Appendix 2 Equality Impact Assessment 49 Type of Document Guidance Guidance Guidance Title Author Date Version Ratifying Committee Heart Failure Specialist Nurse Service: Pharmacological Management of Heart Failure Heart Failure Specialist Nurse Service: Pharmacological Management of Heart Failure Heart Failure Specialist Nurse Service: Pharmacological Management of Heart Failure Jo Topps/ Linda Edmunds 18/02/14 1 Medicines Management Committee Jo Topps 20/05/14 2 Medicines Management Committee Tracey Worland 22/09/16 3 medicines Management Committee

3 1. Introduction Heart failure is a syndrome and can be defined as an abnormality of cardiac structure or function leading to failure of the heart to deliver oxygen at a rate in line with the requirements of the metabolising tissues, despite normal filling pressures (or only at the expense of increased filling pressures). North Somerset Community Partnership s Heart Failure Specialist Nurses (HFSN) Service is commissioned to assist with the management and care of patients diagnosed with heart failure with reduced ejection fraction (HFrEF), within the area of North Somerset. These guidelines may also assist GPs to manage Heart Failure patients in primary care. 2. Purpose / Objective of the Document To support the Heart Failure Specialist Nurse Service to achieve the following: To relieve symptoms with evidence based treatment, therefore improving quality of life and delaying disease progression. To monitor the effects of treatment to ensure delivery of safe and appropriate medication therapy To empower patients through education about the disease process and their consequent treatment Please note: pregnant and breastfeeding women are outside the scope of these guidelines and must be referred to a Consultant Cardiologist 3. Responsibilities Wherever possible the medicines prescribed or recommend by the HFSN should be those included in the Bristol, North Somerset and South Gloucestershire (BNSSG) Medicines Formulary. The HFSN should seek advice from Consultant Cardiologists or other specialist whenever further advice is required to optimise patient care. In individual patient cases and on the advice of a cardiologist the Heart Failure Specialist Nurses may use an accelerated version of these guidelines or alter treatment pathway according to patient clinical status and need. 4. Process Whilst on the Heart Failure Specialist Nurse s caseload the service should: Confirm diagnosis of heart failure caused by left ventricular systolic dysfunction Define the precise underlying cardiac cause of heart failure. Assess clinical status to enable monitoring of treatment effect

4 Initiate/recommend initiation of appropriate pharmacological and non-pharmacological treatment Monitor treatment effect and amend or recommend amendment to pharmacological and non-pharmacological treatment as necessary according to clinical status All Patients referred to the Heart Failure Service must have a confirmed diagnosis of Heart Failure with reduced Ejection Fraction (HFrEF) confirmed on Echocardiogram (Echo). Identification of Causes of Heart Failure Once the diagnosis of Heart Failure is confirmed, it is important to define the precise underlying cardiac cause, particularly if this is correctable; potential causes of heart failure are listed in Table 1. A clinical history, results of echocardiogram (Echo) and electrocardiogram (ECG) in addition to the following blood tests (sodium, potassium, calcium, urea/blood urea nitrogen, creatinine, egfr, liver enzymes, bilirubin, ferritin/tibc, thyroid function, full blood count) are usually sufficient to establish a working theory of cause of heart failure. Specialist Cardiologist advice and specialist diagnostic tests may be required to establish cause in a very small number of cases. Assess clinical status/decompensation to enable monitoring of treatment effect Symptoms and signs are important in monitoring a patient s response to treatment and stability over time. Persistence of symptoms despite treatment usually indicates the need for additional therapy; worsening of symptoms is a serious development placing the patient at risk of urgent hospital admission and death. All patients should be classified using the New York Heart Association (NYHA) Classification of Heart Failure Symptoms (Table 2) this is a functional, symptomatic classification not a classification of disease severity. Symptoms and signs are important in monitoring a patient s response to treatment and stability over time. (Table 3)

5 Table 1 Aetiology of Heart Failure Table 2 New York Heart Association (NYHA) Classification

6 Class I Class II Class III Class IV No limitation of physical activity. Ordinary physical activity does not cause undue breathlessness, fatigue or palpitations. Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue, or palpitations. Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in undue breathlessness, fatigue, or palpitations. Unable to carry on any physical activity without discomfort. Symptoms at rest can be present. If any physical activity is undertaken, discomfort is increased. Table 3 Symptoms and signs typical of Heart Failure Treatment Options for HFrEF

7 Diuretics to relieve symptoms and signs of congestion IF LVEF <35% despite OMT or a history of symptomatic VT/VF, implant ICD Therapy with ACE-I and beta-blocker (Up-titrate to maximum tolerated evidence-based doses) Still Symptomatic and LVEF <35% No Yes Add MR antagonist (up-titrate to maximum tolerated evidence-based dose) Yes Still Symptomatic and LVEF 35% No Yes Able to tolerate ACEI (or ARB) Sinus rhythm QRS duration >130 msec Sinus Rhythm, HR >70 bpm ARNI to replace ACE-I Evaluate need for CRT Ivabradine These above treatments may be combined if indicated Resistant symptoms Consider digoxin or H-ISDN No further action required consider reducing diuretics Therapeutic algorithm for a patient with symptomatic heart failure with reduced ejection fraction. ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; ARNI = angiotensin receptor neprilysin inhibitor; BNP = B-type natriuretic peptide; CRT = cardiac resynchronization therapy; H-ISDN = hydralazine and isosorbide dinitrate; HR = heart rate; ICD = implantable cardioverter defibrillator; LBBB = left bundle branch block; LVEF = left ventricular ejection fraction; MR = mineralocorticoid receptor; NT-proBNP = N-terminal pro-b type natriuretic peptide; NYHA = New York Heart Association; OMT = optimal medical therapy; VF = ventricular fibrillation; VT = ventricular tachycardia. Symptomatic = NYHA Class II-IV. If ACE inhibitor not tolerated/contra-indicated, use ARB. Adapted from ESC guidelines 2016

8 ACE INHIBITORS IN HEART FAILURE ACE inhibitors (ACE-I) improve symptoms and exercise capacity, reduce the risk of Heart Failure hospitalisation, and increase survival. Clinical judgement should be used to determine whether an ACE-I or beta blocker should be started first. Indications: Potentially all patients with HF (NYHA II-IV) and an EF <40% First-line treatment (along with beta-blockers); start as early as possible in the course of disease. ACE inhibitors are also of benefit in patients with asymptomatic HFrEF (NYHA class I) Contraindications: History of angioedema (hereditary, idiopathic or previously with ACE I or AIIRA) Known bilateral renal artery stenosis Known severe stenosis of artery supplying a single functioning kidney Current angiotensin II receptor blocker therapy (do not combine an ACE-I and AIIRA) Cautions: Use with care or avoid with aortic or mitral valve stenosis Increased risk of first dose hypotension in patients taking high doses of diuretic, on a low sodium diet, on dialysis, dehydrated or with decompensated heart failure Correct volume depletion before initiation Peripheral vascular disease or generalised atherosclerosis due to risk of clinically silent renovascular disease Hepatic impairment discuss with cardiologist. Moderate renal insufficiency and/or a relatively low BP are not contraindications to ACE inhibitor treatment, but patient may require a reduced dose at initiation and a slow dose titration with careful monitoring of U&E s. Seek specialist advice before initiation: Aortic valve stenosis Hyponatraemia (Na+ <133mol/L) Hyperkalaemia (K+ >5.5 mmol/l or trend of increasing potassium with unknown cause) Renal dysfunction (creatinine >200 μmol/l or egfr <30 ml/min/1.73 m2) Symptomatic or severe asymptomatic hypotension (systolic BP <100 mmhg) Important Interactions (see BNF for full information): Avoid non-steroidal anti-inflammatory drugs (NSAIDs) Avoid preparations that may contribute to a serum potassium rise e.g. Trimethoprim, cotrimoxazole, K+ supplements, Low-salt substitutes with a high K+ content, K+sparing diuretics (amiloride, co-amilofruse, co-amilozide). Care with aldosterone antagonists (spironolactone, eplerenone). Avoid renin inhibitors (Aliskiren) Vasodilator therapy (such as Isosorbide Mononitrate) may need to be reviewed before ACE-I initiation.

9 Potential side effects: Cough, hypotension, syncope, renal insufficiency, hyperkalaemia, angioedema, cerebral hypoperfusion, rash, pancreatitis, upper respiratory tract symptoms, gastro intestinal disturbance, altered liver function tests, blood disorders, headache, dizziness, fatigue, taste disturbance. ACE Inhibitor titration regime (BNSSG Formulary choices): (slower titration may be appropriate depending on clinical condition) Perindopril Dose & Ramipril Lisinopril Erbumine frequency Week mg OD 2.5 mg OD 2 mg OD Week mg BD 5 mg OD 4 mg OD Week mg BD 10 mg OD Week 7 5mg BD 20 mg OD Week 9 Week 11 Formulary across BNSSG Yes 1 st line 30 mg OD 35 mg OD Yes 1 st line Yes 2 nd line only Target dose 5mg BD 20 35mg OD 4mg OD Ace Inhibitor titration regime (Non-Formulary) Patients who are symptomatic on a non-formulary ACE-I should be switched to a formulary choice. Roughly equivalent doses are shown in the table below although be aware of intra patient variation. Consider switching to a lower equivalent dose to ensure patient tolerates the new medication. Ramipril Enalapril Trandolapril Captopril 1.25mg od 2.5mg od 2.5mg 0.5mg od 6.25mg tds bd 2.5mg od 5mg bd 1mg od 12.5mg tds 2.5mg bd 10mg bd 2mg od 25mg tds 5mg bd 20mg bd 4mg od 50mg tds

10 If unable to switch to BNSSG formulary choice, titrate current medication: Dose & frequency Enalapril Trandolapril Captopril Week 1 2.5mg OD 500 micrograms OD 6.25 mg TDS Week 3 2.5mg BD 1mg OD 12.5 mg TDS Week 5 5mg BD 2mg OD Week 7 10mg BD 4mg OD 12.5 mg mane 12.5 mg 2pm 25 mg nocte 25 mg mane 12.5 mg 2pm 25 mg nocte Week 9 20mg BD 25 mg TDS Week 11 Week mg mane 25 mg 2pm 50 mg nocte 50 mg mane 25 mg 2pm 50 mg nocte Week 15 Formulary across BNSSG 50 mg TDS No No No Target dose mg BD 4 mg OD 50 mg TDS Advice to patient Explain expected benefits of treatment Explain symptoms should improve a few weeks to a few months after drug initiation Explain details of possible adverse effects Advise patients to report adverse effects Explain the necessity for blood test monitoring Advise patients to avoid NSAIDs including purchased and salt substitutes high in K+ Remind patient not to discontinue medication without seeking medical advice Explain rare risk of angioedema and what to do if this happens Monitoring: Baseline blood pressure and U&Es Recheck U&Es 7-10 days after starting ACE-I and after each dose increase (if potassium > 5.1 mmol/l ensure potassium is rechecked in 7 days) See table below to manage changes in egfr and potassium

11 Managing adverse effects and worsening symptoms: Cough Exclude cough due to heart failure or other concomitant disease e.g. respiratory disease or pulmonary oedema. A cough that is clearly related to the ACE inhibitor could be substituted for an Angiotensin II receptor antagonist following consultation. Cerebral hypo-perfusion presents as dizziness, blackouts, light-headedness etc. Can be resolved by a reduction in concomitant medication i.e. diuretics, nitrates, beta-blockers and calcium-channel blockers following medical consultation. Asymptomatic Hypotension does not usually require any change in therapy. Symptomatic Hypotension consider reduction/discontinuation of other antihypertensives, nitrates and other vasodilators. If no signs of fluid overload consider reducing diuretic dose. Renal dysfunction small increases in urea, creatinine and potassium are common and acceptable. See table below for acceptable limits. Changes in U&Es following ACE-inhibitor initiation and titration: Potassium Significant change in renal function Moderate change in renal function Monitoring Action Investigate causes Potassium Stop ACE-I New medication >6.5mmol/L (e.g Potassium Stop ACE-I. spironolactone, >6.0mmol/L Recheck in 24 eplerenone, hours. amiloride, K + supplements). Lo-salt Potassium mmol/L Creatinine >200 umol/l (or increase by >30%) egfr <30mL/min (or decrease by > 25%) Creatinine increase by <30% egfr decrease by <25% Recheck in 24 hours Stop ACE-I. Recheck in 24 hours Do not modify ACE-I dose. Monitor closely (repeat U&Es weekly) Overdiuresis or dehydration. Concomittant medication (e.g. NSAIDS) Further action Seek urgent advice or admit Seek advice about restarting ACE-I at lower dose. If remains elevated seek advice Seek advice about restarting ACE-I at lower (or previously tolerated dose) Seek advice if progressive decline in egfr If the patient has not tolerated ACE inhibitor therapy, consider Angiotensin II receptor antagonist as an alternative therapy.

12 ACE INHIBITOR GUIDELINES Yes Consider contraindications, cautions and interactions is patient suitable for ACE-I treatment? No Week 1: Advise patient about treatment Discuss with Consultant Cardiologist Complete clinical assessment: check U&Es, weight, symptoms, heart rate, blood pressure. Is Systolic BP <100mmHg OR Creatinine >200umol/L OR Potassium >5.5mmol/L? Yes No Do not initiate treatment. Discuss with Consultant Cardiologist Initiate 1 st dose of first line ACE inhibitor. Arrange for U&Es to be checked in 7-10 days (if baseline K+ > 5.1 mmol/l - check in 7 days) WEEK 3 Clinical assessment of patient. If patient tolerating dose, increase to next titration dose. Inform patient of dose change. Arrange for U&Es to be checked in 7-10 days. WEEK 5 Clinical assessment of patient. If patient tolerating dose, increase to next titration dose. Inform patient of dose change. Arrange for U&Es to be checked in 7-10 days. EVERY TWO WEEKS UNTIL PATIENT REACHED MAXIMUM DOSE OR MAXIMUM TOLERATED DOSE. Clinical assessment of patient. If patient tolerating dose, increase to next titration dose. Inform patient of dose change. Arrange for blood test in 7-10 days. HFSN to check blood results on final visit. Inform GP of need to monitor bloods 6 monthly or more frequently if clinically indicated

13 THE USE OF ANGIOTENSIN II RECEPTOR ANTAGONISTS Indications: Angiotensin II receptor antagonists (AIIRA) also known as angiotensin receptor blockers (ARB) may be used as an alternative to ACE inhibitors only if the patient is intolerant of an ACE inhibitor due to persistent cough. Contraindications: Renal artery stenosis or stenosis of the artery to a single functioning kidney Angioedema during previous Angiotensin II receptor antagonist therapy or previous ACE inhibitor therapy Severe hepatic impairment Current ACE-inhibitor therapy (do not combine an ACE-I and AIIRA) Cautions Increased risk of first dose hypotension in patients taking high dose of diuretic, on a low sodium diet, on dialysis, volume depleted or with decompensated heart failure Use with care in peripheral vascular disease or generalised atherosclerosis owing to the risk of clinically silent reno-vascular disease Renal function should be monitored before and during treatment. A reduced dose in renal impairment may be required. (Moderate renal insufficiency and a relatively low BP are not contraindications to treatment but may require close monitoring) Volume depletion should be corrected before starting treatment Use with care or avoid with aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy Seek specialist advice before initiation: Severe heart failure (NYHA class IV) Aortic valve stenosis Hypovolaemia Hyponatraemia (Na+ <133mmol/L) Hyperkalaemia (K+ >5.5mmol/L or trend of increasing potassium with unknown cause) Renal dysfunction (creatinine >200 μmol/l or egfr <30 ml/min/1.73 m2) Symptomatic or severe asymptomatic hypotension (systolic BP <100 mmhg) High dose diuretic therapy (e.g. > 80mg Furosemide daily or equivalent) Important Interactions (see BNF for full information): Avoid non-steroidal anti-inflammatory drugs (NSAIDs) Avoid preparations that may contribute to a serum potassium rise e.g. Trimethoprim, cotrimoxazole, K+ supplements, Low-salt substitutes with a high K+ content, K+sparing diuretics (amiloride, co-amilofruse, co-amilozide). Care with aldosterone antagonists (spironolactone, eplerenone) Avoid renin inhibitors (Aliskiren) Vasodilator therapy (such as Isosorbide Mononitrate) may need to be reviewed before ACE-I initiation.

14 Potential side effects: Side effects are usually mild, symptomatic hypotension may occur, particularly in patients with intra vascular volume depletion. Hyperkalaemia occurs occasionally, angioedema has also been reported. Licensing and titration: Drug Licensed BNSSG Formulary Candesartan Yes Yes first line Losartan Yes Yes first line Valsartan Yes No Irbesartan No hypertension only No AIIRA titration regime (BNSSG Formulary choices): (Slower titration may be appropriate depending on clinical condition) Dose & Candesartan Losartan frequency Week 1 4mg od 12.5mg od Week 3 8mg od 25mg od Week 5 16mg od 50mg od Week 7 32mg od 100mg od Week 9 150mg od Target dose 32mg OD 150mg OD Advice to patient: Explain expected benefits of treatment Explain symptoms should improve a few weeks to a few months after drug initiation Explain details of possible adverse effects Advise patients to report adverse effects Explain the necessity for blood test monitoring Advise patients to avoid NSAIDs (including OTC) and salt substitutes high in potassium (e.g. Lo-salt) Remind patient not to discontinue medication without seeking medical advice Explain rare risk of angioedema and what to do if this happens Monitoring: Baseline blood pressure and U&Es Recheck U&Es 7-10 days after starting AIIRA and after each dose increase (if baseline potassium is > 5.1 mmol/l, ensure potassium checked in 7 days) See table below to manage changes in egfr and potassium

15 Managing adverse effects and worsening symptoms: Cerebral hypo-perfusion Presents as dizziness, blackouts, light-headedness etc. Can be resolved by a reduction in concomitant medication i.e. diuretics, nitrates, beta-blockers and Calcium-channel blockers following medical consultation. Symptomatic Hypotension Consider reduction/discontinuation of other antihypertensives, nitrates, calcium channel blockers and other vasodilators. If no signs of fluid overload, consider reducing diuretic dose. Asymptomatic Hypotension Does not usually require any change in therapy Renal dysfunction Small increases in urea, creatinine and potassium are common and acceptable. See table below for acceptable limits. Changes in U&Es following AIIRA initiation and titration: Potassium Significant change in renal function Moderate change in renal function Monitoring Action Investigate causes Potassium Stop AIIRA New medication >6.5mmol/L (e.g Potassium Stop AIIRA. spironolactone, >6.0mmol/L Recheck in 24 eplerenone, hours. amiloride, K + supplements). Lo-salt Potassium mmol/L Creatinine >200 umol/l (or increase by >30%) egfr <30mL/min (or decrease by > 25%) Creatinine increase by <30% Recheck in 24 hours Stop AIIRA. Recheck in 24 hours Do not modify AIIRA dose. Monitor closely (repeat U&Es weekly) Overdiuresis or dehydration. Concomitant medication (e.g. NSAIDS) Further action Seek urgent advice or admit Seek advice about restarting AIIRA at lower dose. If remains elevated seek advice Seek advice about restarting AIIRA at lower (or previously tolerated dose) Seek advice if progressive decline in egfr

16 ANTGIOTENSIN II RECEPTOR ANTAGONIST GUIDELINES Yes Consider contraindications, cautions and interactions is patient suitable for AIIRA treatment? No Week 1: Advise patient about treatment Discuss with Consultant Cardiologist Complete clinical assessment: HR, BP, check U&Es, weight Is Systolic BP <100mmHg OR Creatinine >200umol/L OR Potassium >5.5mmol/L Yes No Do not initiate treatment. Discuss with Consultant Cardiologist Initiate 1 st dose of first line AIIRA Arrange for U&Es to be checked in 7-10 days (if baseline K+ > 5.1 mmol/l - check in 7 days) WEEK 3 Clinical assessment of patient. If patient tolerating dose, increase to next titration dose. Inform patient of dose change. Arrange for U&Es to be checked in 7-10 days. WEEK 5 Clinical assessment of patient. If patient tolerating dose, increase to next titration dose. Inform patient of dose change. Arrange for U&Es to be checked in 7-10 days EVERY TWO WEEKS UNTIL PATIENT REACHED MAXIMUM DOSE OR MAXIMUM TOLERATED DOSE. Clinical assessment of patient. If patient tolerating dose, increase to next titration dose. Inform patient of dose change. Arrange for blood test in 7-10 days. HFSN to check blood results of final visit. Inform GP of need to monitor bloods 6 monthly or more frequently if clinically indicated

17 BETA-BLOCKERS IN HEART FAILURE Beta-blockers licensed for use in heart failure should be offered to all patients with stable, symptomatic HFrEF. Clinical judgement should be used to decide whether to start a betablocker or ACE inhibitor first. Patients who develop heart failure due to HFrEF and who are already on beta-blocker treatment should be switched to a beta-blocker licensed for heart failure. Indications: Potentially all patients with mild or moderate systolic heart failure (EF < 40%) Clinically stable - no recent admission to hospital with heart failure or episode of decompensation within the last 4 weeks No recent adjustment to cardiac medication in the last two weeks Heart rate >60 bpm, systolic blood pressure >100 mmhg Beta-blockers are also of benefit in patients with asymptomatic LV systolic dysfunction (NYHA class I) Contraindications: Decompensated heart failure Severe bradycardia (heart rate <60 bpm) 2nd or 3rd degree AV block Sick sinus syndrome (including Sino atrial block) Cardiogenic shock Documented adverse reaction to specific beta-blockers previously Severe peripheral vascular disease Prinzmetals angina Diabetics with frequent episodes of hypoglycaemia Phaeochromocytoma Cautions: COPD: Consider for all patients with COPD without reversibility. Diabetes: Beta-blockers may cause hypoglycaemia, mask the symptoms of hypoglycaemia and also enhance the hypoglycaemic effects of Insulin. Monitor blood glucose regularly, and adjust hypoglycaemic medication as necessary. Renal Impairment: Reversible deterioration of renal function during beta-blocker therapy can occur in patients with systolic blood pressure below 100mmHg, ischaemic heart disease, or underlying renal insufficiency (monitor electrolytes) Seek specialist advice before initiation: Severe hypotension (systolic blood pressure below 100mmHg) Patients already taking a non-selective beta blocker Asthma: a cardio selective beta-blocker (bisoprolol or nebivolol) should be selected and initiated at a low dose by a specialist and the patient closely monitored for adverse effects Severe heart failure (NYHA class IV) beta blocker may need to be initiated in hospital Concurrent use of rate limiting calcium-channel blockers (verapamil, diltiazem) (consideration should be given to stopping these in heart failure patients after discussion with Cardiologist)

18 Important Interactions (see BNF for full information): Digoxin: Serum digoxin levels may increase. Monitor and adjust digoxin levels as necessary during titration period. Hypotensive agents: The effects of beta-blockers may potentiate the hypotensive effects of other cardiac drugs. Extreme care required with rate controlling medication such as amiodarone, ivabradine, verapamil and diltiazem (risk of bradycardia, AV block and myocardial depression). Discuss with cardiologist before using concurrent treatment to determine if rate controlling medication can be modified. Potential side effects (most common): Bradycardia, worsening of heart failure symptoms, hypotension, fatigue, gastrointestinal disturbances, conduction disorders, peripheral vasoconstriction, bronchospasm, sleep disturbances, sexual dysfunction. Beta-blockers may cause hypoglycaemia and mask symptoms of hypoglycaemias in diabetics. Drug choice and titration regime: Drug Licensed BNSSG Formulary Cardio-selective Bisoprolol Any stage of heart failure First line Yes Carvedilol with ACE-I and diuretics Second line No Nebivolol Mild to moderate heart failure in patients > 70 years Only to be used on advice from Consultant Cardiologist Beta blocker titration regime (BNSSG Formulary choices): (Slower titration may be appropriate depending on clinical condition) Yes Dose & Bisoprolol Carvedilol Nebivolol frequency Week mg od 3.125mg bd 1.25mg od Week 3 2.5mg od 6.25mg bd 2.5mg od Week mg od 12.5mg bd 5mg od Week 7* 5mg od 25mg bd 10mg od Week 11* 7.5mg 50mg bd (if weight > 85kg) Week 16 10mg od Target dose 10mg od 25mg bd (50mg bd if weight > 85kg) 10mg od

19 *Note above bisoprolol 5mg daily, doses should be titrated every 4 weeks Patient Advice: Explain the known benefits of the therapy, but that it may be some time before they feel the real benefits They may feel worse initially and what they should do if they feel unwell (if bronchospasm is suspected seek immediate medical help) Advise patient to report any deterioration in symptoms Advise not to drive if feeling faint or dizzy Warn patients who wear contact lenses of possible dry eyes Encourage patient never to stop beta-blockers before seeking advice If patient is diabetic, advise on the risk of masking symptoms of hypoglycaemia with beta blockers. Monitoring: Baseline blood pressure, heart rate, U&Es, weight and electrocardiogram (unless results available from recent ECG (within 2 months) and patient clinically stable). Check U&Es when patient has reached maximum dose or maximum tolerated dose. Managing adverse effects and worsening symptoms: Worsening symptoms: (Increased dyspnoea, fatigue, oedema, weight gain of >2kg in 2 weeks or less) Do not further up titrate beta-blocker dose until symptoms stable Consider increasing dose of diuretic therapy; check U&Es and review patient in 2 days Consider decreasing dose of beta-blocker if increasing dose of diuretic not effective If marked fatigue consider temporarily reducing beta-blocker Review patient in one week if no improvement discuss with Cardiologist If serious deterioration in condition half or stop dose and seek advice from Cardiologist Bradycardia: (<50 bpm) Do not increase beta-blocker dose further If bradycardic with worsening symptoms halve dose or, severe deterioration in symptom stop beta- blocker. Discuss with consultant cardiologist. Discuss role of other rate limiting drugs (Diltiazem, Verapamil, Digoxin, Amiodarone) with Consultant to consider if these could be stopped or reduced If patient taking digoxin, consider checking Digoxin plasma level If heart rate <50 bpm record ECG to exclude heart block Symptomatic hypotension: (<100 mmhg associated with dizziness, fainting, confusion) Check U&Es to exclude other causes for symptoms. Consider reducing diuretic. Consider stopping any vasodilating drugs (nitrates, calcium-channel blockers) after discussion with Cardiologist If unresolved reduce dose or stop beta-blocker after seeking advice Wait four weeks before considering further titration or re- introduction of beta blockers

20 Non-symptomatic hypotension: (<100mmHg) Do not increase beta-blocker dose until blood pressure improves If beta blocker dose is not optimised monitor blood pressure and up titrate if blood pressure allows in future Diabetics If masking of hypoglycaemic symptoms occurs discuss with patients diabetes specialist to facilitate diabetic review. A temporary reduction in beta blocker dose may be required to maintain patient s immediately safety.

21 BETA-BLOCKER GUIDELINES Yes Consider contraindications, cautions and interactions is patient suitable for beta-blocker treatment? No WEEK 1 Discuss treatment with patient. Complete clinical assessment, ECG, baseline U&Es, HR>60bpm, BP, Symptoms, Weight Initiate 1 st dose Discuss with appropriate Consultant Cardiologist Week 3 - Patient tolerating dose. Increase dose. Inform patient of change to drug dosage Week 5 Patient tolerating dose. Increase dose. Inform patient of change to drug dosage Week 7 Patient tolerating dose. Increase dose. Inform patient of change to drug dosage CONTINUE UNTIL TOLERATED / TARGET DOSE ACHIEVED Patient not tolerating dose. Consider reducing dose to previous dose or stopping beta blocker. Patient at target or maximum tolerated dose. Check U&Es and inform patient s GP of current treatment and monitoring plan. NOTE: In IHD if beta-blockers are to be stopped, a gradual reduction in the beta-blocker dose is advisable in order to avoid exacerbation of angina

22 LOOP DIURETICS IN HEART FAILURE Loop diuretics should be routinely used for the relief of congestive symptoms and fluid retention in patients with heart failure, and titrated (up and down) according to need following the initiation of subsequent heart failure therapies. Diuretic therapy should be continually reviewed to ensure patient is maintained on the lowest dose of diuretic that controls symptoms. Indications: Confirmed diagnosis of Left Ventricular Systolic Dysfunction on echocardiogram or angiogram Clinical assessment shows signs of fluid oedema Contraindications: Anuria Severe hypokalaemia (potassium < 3.5 mmol/l) Severe hyponatraemia (sodium < 133 mmol/l) Liver cirrhosis Cautions: Hypotension Liver failure Prostatic enlargement Ensure adequate hydration Volume depletion Seek specialist advice before initiation: Renal dysfunction: discuss with specialist if creatinine > 200 μmol/l or egfr < 30 ml/min Important Interactions (see BNF for full information): Enhanced hypotensive effect when given with antihypertensive agents (e.g. ACE-I, alphablockers calcium channel blockers) Increased risk of postural hypotension when given with tricyclic antidepressants (e.g. amitriptyline) Increased risk of nephrotoxicity with NSAIDs and antagonism of diuretic effect. Risk of hypokalaemia with diuretics can increase risk of arrhythmias with digoxin, amisulpride, pimozide. Potential side-effects: Electrolyte disturbance (Hypokalaemia, Hyponatremia, Hypomagnesaemia), Hyperuricaemia /Gout, hypovolaemia, Renal impairment, Hypoglycaemia(less common than thiazide diuretics)

23 Licensing and titration Drug Licensed BNSSG Formulary Furosemide Yes First line Bumetanide Yes Second line Initial Dose 40mg od (20mg od in elderly) 1mg od (500 micrograms od in elderly) Dose increments 20 40mg daily 500 micrograms 1mg daily Usual daily dose 20mg od 80mg bd (higher doses may be required in renal impairment) 500microgram od 5mg od (higher doses may be required in renal impairment) Patient Advice: Time of taking the loop diuretic is not fixed, however it is better to avoid taking after 4pm as this can lead to nocturia. Report dizziness/light headedness as this may be indicative of over treatment Encourage patient to weigh themselves daily and report sudden sustained weight increase or decrease (more than 1kg over 3 days) to specialist nurse. Report other symptoms of fluid overload i.e. increased breathlessness, frothy sputum, and peripheral oedema to specialist nurse. Diarrhoea, vomiting, and poor fluid intake exacerbate dehydration contact specialist nurse if these persist for > 48 hours. Gout can occur (advise patient about symptoms) Monitoring: Baseline blood pressure and U&Es Check U&Es 5-7 days after initiation and each dose change Managing adverse effects and Worsening Symptoms; Worsening Symptoms: (increased dyspnoea, fatigue, oedema, weight gain) There is anecdotal evidence that Bumetanide induces greater diuresis than Furosemide in patients with intra-abdominal oedema. Consider changing to Bumetanide in patients with intra-abdominal oedema due to its higher bioavailability. (Furosemide 40mg is equivalent to Bumetanide 1mg). Consider increasing dose of diuretic if the patient shows a weight gain that is sustained for >3 days and is a significant increase in weight (1-2 kgs or more) above dry weight, especially if this is accompanied by an increase in peripheral oedema, JVP or symptoms of breathlessness. Review in one week, if no improvement, consider further dose increase or discuss with cardiologist. Discuss possible plan with patient for increasing medication in future if clinically needed

24 Symptomatic Hypotension: (systolic BP <100mmHg with dizziness, fainting, confusion) Check U&Es to exclude other causes for symptoms Consider reduction in diuretic therapy if clinically stable Review patient within 7 days after reduction in dose to monitor response If no improvement in one week discuss with cardiologist LOOP DIURETIC GUIDELINES Yes Consider contraindications, cautions and interactions is patient suitable for loop diuretic? No Discuss treatment with patient. Complete clinical assessment, weight, HR, BP, oedema, JVP, baseline U&Es. Discuss with Consultant Cardiologist Consider loop diuretic (Furosemide 20-40mg od or Bumetanide 500mcg - 1mg od) Review in 7 days Assess response to treatment Repeat U&Es. Adequate response (Improved symptoms weight reduction 0.5kg/day) Inadequate response (no improvement in symptoms; weight stable or increased) Renal function stable Renal function stable Significant deterioration in renal function Maintain dose Consider increasing dose Discuss with Consultant Cardiologist Review of diuretic dose (up or down) at each consultation depending on clinical symptoms. Check U&Es 7 10 days after each dose increase.

25 THIAZIDE DIURETICS IN HEART FAILURE In patients with resistant oedema, bendroflumethiazide may be added to a loop diuretic to improve diuresis. Extreme caution must be used as this can cause a dramatic diuresis and resulting disturbance of fluid and electrolyte balance. This is usually a temporary measure under the guidance of a Consultant Cardiologist. (In resistant oedema consider checking serum Albumin and urinary Albumin Creatinine Ratio (ACR) to exclude Nephrotic Syndrome) Indications: Confirmed diagnosis of left ventricular systolic dysfunction Patients with resistant oedema despite treatment with adequate dose and duration of loop diuretic Check baseline blood pressure and U&Es (care if creatinine > 200umol/L) Frail elderly patients or those living alone may not be suitable for the addition of a thiazide due the risk of hypotension (consider arranging support to maintain patient safety) Contraindications: Refractory hypokalaemia (potassium < 3,5mmol/l) Hyponatraemia (sodium < 133mmol/l) Hypercalcaemia (corrected calcium > 2.6mmol/l) Symptomatic Hyperuricaemia (symptoms of gout) Addison s Disease Severe liver Disease Cautions: Close monitoring of electrolytes is required during treatment due to the risk of hypokalaemia May exacerbate diabetes and gout Renal impairment Hepatic impairment mild to moderate May exacerbate Systemic Lupus Erythematosus Important Interactions (see BNF for full information): Enhanced hypotensive effect when given with antihypertensive agents Increased risk of postural hypotension when given with tricyclic antidepressants (e.g amitriptyline) NSAIDs increased risk of nephrotoxicity and antagonism of diuretic effect Risk of Hypokalaemia caused by diuretics can lead to Arrhythmias with Digoxin, Amisulpride, Pimozide. Potential side effects: Mild gastro-intestinal disturbances, postural hypotension, Hypokalaemia, Hypomagnesaemia, Hyponatraemia, Hypercalcaemia, impotence, Hypochloraemic alkalosis, Hyperuricaemia, gout, altered plasma lipid concentrations, altered plasma glucose levels.

26 Licensed doses and titration: Drug Bendroflumethiazide Indapamide Metolazone Licensed Yes for oedema No Only unlicensed stock available BNSSG Formulary Yes (for hypertension) (for use in combination with Loop diuretic) Discuss use with consultant cardiologist Initial Dose 2.5-5mg od (or alternate days) Dose increments 2.5mg od Usual daily dose 2.5-5mg two or three times weekly n/a n/a n/a n/a n/a n/a Patient Advice: Time of taking the thiazide diuretic is not fixed, however it is better to avoid taking after 4pm as this can lead to Nocturia Warn patient of likely increase in diuresis Report dizziness/light-headedness as this may be indicative of over treatment Encourage patient to weigh themselves daily and report sudden sustained weight increase or decrease (more than 1kg over 3 days) to specialist nurse. Report other symptoms of fluid overload i.e. increased breathlessness, frothy sputum, and peripheral oedema to specialist nurse. Diarrhoea, vomiting, and poor fluid intake exacerbate dehydration contact specialist nurse if these persist for > 48 hours. Monitoring: Check baseline U&Es and weight Review patient and weight after 72 hours of initiation and dose changes Monitor U&Es 7 days after each dose change Review patient to monitor clinical response to thiazide and withdraw or reduce therapy as appropriate Managing adverse effects and worsening symptoms: Worsening Symptoms: (increased dyspnoea, fatigue, oedema, weight gain) Consider increasing dose of diuretic (after discussion with Consultant cardiologist) if the patient shows a weight gain that is sustained for >3 days and is a significant increase in weight (1-2 kgs or more) above dry weight, especially if this is accompanied by an increase in peripheral oedema, JVP or symptoms of breathlessness. Discuss possible plan with patient for increasing medication in future if clinically needed

27 Symptomatic Hypotension: (systolic BP <100mmHg with dizziness, fainting, confusion) Check U&Es to exclude other causes for symptoms Consider reduction in diuretic therapy if clinically stable Review patient 1 week after reduction in dose to monitor response If no improvement in one week discuss with Consultant cardiologist Renal dysfunction: U&Es should be checked at least weekly on initiation of treatment Some deterioration in renal function is commonly seen during the addition of a thiazide to loop diuretic but renal function generally returns to baseline after treatment If creatinine increases to >200umol/L, seek advice from Consultant cardiologist

28 Thiazide Diuretics guidelines Consider contra-indications, cautions and interactions Is patient suitable for thiazide diuretic? Yes No Discuss treatment with cardiologist Discuss care with consultant cardiologist for next steps Is patient on optimised dose of loop diuretic? Yes Start thiazide diuretics No Consider if increase of loop diuretic appropriate Review in 7 days with repeat U&E s Adequate response Yes No Reduce diuretic therapy if clinically stable Discuss care with consultant cardiologist for next steps

29 Mineralocorticoid Receptor Agonists (MRA) Patients with Heart Failure with reduced Ejection Fraction (HFrEF) and LVEF 35% that remain moderate-severely symptomatic (NYHA Class II-IV) despite optimal therapy should be considered for an Aldosterone antagonist licensed for heart failure (Spironolactone or Eplerenone). Spironolactone should be used first line. Eplerenone is classified as TLS Amber in BNSSG and therefore patients who are symptomatic and intolerant of Spironolactone should be discussed with cardiologist for consideration of Eplerenone. See BNSSG Shared Care Protocol for Eplerenone ( for further advice and monitoring. Indications: Potentially all patients with persisting symptoms (NYHA Class II IV) and have an LVEF 35% despite treatment with an ACE-I (or AIIRA) and beta-blocker Contraindications: Known allergic reaction/hypersensitivity to MRA Hyponatraemia (sodium < 133 mmol/l) Hypercalcaemia (corrected calcium > 2.6 mmol/l) Addisons disease Anuria CKD stage 4-5 Concomitant potassium sparing diuretic or potassium supplements review treatment Cautions (consider lower dose) Elderly Hepatic impairment (risk of precipitating encephalopathy) Acute porphyria Seek specialist advice before initiation: Renal impairment - creatinine > 200 umol/l (avoid if rapidly deteriorating or severe impairment) Important Interactions (see BNF for full information): Enhanced hypotensive effect when given in addition to other anti-hypertensives Risk of hyperkalaemia when use with potassium supplements and potassium sparing diuretics. Risk of severe Hyperkalaemia when concomitant use with ACE-Is, ARBs and renin inhibitors (e.g. Aliskiren) Increased risk of postural hypotension when was given concomitantly with tricyclic antidepressants. NSAIDs increased risk of nephrotoxicity and antagonism of diuretic effect Potential side effects:

30 Acute renal failure, diarrhoea and other gastro-intestinal disturbances, gynaecomastia, impotence, lethargy, headache, confusion, rashes, hyperkalaemia (discontinue), hyponatraemia, hepatoxicity. Blood disorders (see BNF), Atrial fibrillation (Eplerenone). Patient advice: Explain the known benefits of treating patients with heart failure with an Aldosterone antagonist Warn of the possible side effects particularly diarrhoea and signs of sodium and water depletion. Inform of the need for, timing and rationale of close blood chemistry monitoring during initiation, titration and ongoing monitoring. Encourage the patient not to discontinue their medication except where diarrhoea/vomiting or intercurrent illness occurs and there is risk of dehydration Monitoring: Monitor baseline U&Es and 7 days after initiation and after each dose increase Managing adverse effects and worsening symptoms: Diarrhoea If diarrhoea occurs as a side effect of an Aldosterone antagonist the drug should be stopped immediately. Gynaecomastia Spironolactone may need to be discontinued. May need to refer to Consultant Cardiologist for consideration of eplerenone Sodium and water depletion due to diarrhoea and vomiting, Intercurrent febrile illness, e.g. chest infection, inadequate fluid intake, or has been in a hot climate, perspiring excessively. Symptoms are postural dizziness/light-headedness or significant and sustained weight loss. Stop aldosterone antagonist temporarily or reduce dose Renal Dysfunction small changes in creatinine and potassium are common and acceptable. See table below for acceptable limits:

31 Changes in U&Es following spironolactone initiation and titration: Monitoring Action Investigate causes Further action Potassium > 6.5mmol/L Stop spironolactone Seek urgent advice or admit Stop Seek advice about Potassium > spironolactone. restarting 6.0mmol/L Recheck in 24 spironolactone at a hours. lower dose Potassium mmol/L Creatinine > 200 umol/l egfr < 30mL/min egfr < 20ml/min Halve dose of spironolactone. Recheck in 24 hours. Halve dose of spironolactone or reduce to previously tolerated dose Stop spironolactone immediately New medication (e.g, ACE-I/ARB, amiloride, K + supplements). Lo-salt Overdiuresis or dehydration. Concomittant medication (e.g. NSAIDS) If remains elevated seek advice Repeat U&Es after 48 hours. Seek advice Repeat U&Es after 48 hours. Seek advice

32 Mineralocorticoid Receptor Antagonist (MRA) Guidelines ACE or ARB Optimised Consider contraindications, cautions and interactions is patient suitable for aldosterone antagonist? No contraindications Contraindications identified don t commence MRA discuss cardiology Recent MI in last 2 weeks Yes No *Eplerenone Previously tried Spironolactone Yes No Tolerated? Spironolactone Yes No Spironolactone *Eplerenone Complete clinical assessment. Take baseline U&Es, HR, BP and weight Continued on next page *Discuss with cardiologist See shared care protocol

33 Continue from previous page Is patient on K+ supplements or K+ sparing diuretic No Yes Stop K+ supplements /sparing diuretic Start spironolactone 12.5 mg 25mg od (lower dose may be appropriate depending on K+, BP and renal function Check U&Es and BP in 7 days. Make appointment 1 month from initiation. Yes Review after 4 weeks Dose tolerated? Increase dose from 12.5mg to 25mg od (or 25mg to 50mg od) Ensure U&Es taken at 7 days. Make appointment for 1 month after increase No Consider reducing spironolactone dose and seek advice Review 4 weeks after increase Dose tolerated? Yes U&Es must be checked monthly for 2 more months, then every 3 months for 1 year then every 6 months No Seek medical advice

34 DIGOXIN IN HEART FAILURE Cardiac glycosides are indicated in atrial fibrillation in order to control ventricular rate and thereby improve ventricular function and any degree of symptomatic heart failure. In sinus rhythm, digoxin may reduce the risk of hospitalisation for worsening heart failure symptoms, although it has not been tested in addition to optimal therapy (ACE I, betablocker, Aldosterone antagonist). Withdrawal of digoxin in stable heart failure patients may exacerbate symptoms. Therefore digoxin is indicated for symptom control in patients already on optimal treatment to decrease the risk of hospitalisation for heart failure without impact on survival. Initiation must be discussed with a Consultant Cardiologist. Indications: Patients in sinus rhythm with worsening or severe symptomatic heart failure (NYHA class III IV) despite the optimum therapy i.e. ACE inhibitor, diuretic, aldosterone antagonist and beta-blocker therapy. Patients with atrial fibrillation requiring rate control. Contraindications: Second and third degree AV block (especially if there is a history of Stokes-Adams attacks) SVTs with accessory conduction pathways e.g. Wolff-Parkinson White syndrome Hypertrophic cardiomyopathies Hypokalaemia - must be corrected before use Ventricular tachycardia or ventricular fibrillation Myocarditis Known hypersensitivity to digoxin or other digitalis glycosides or any component of the preparation Cautions: Bradycardia heart rate <60bpm- if bradycardia and taking digoxin consider reducing the dose or stopping to allow titration of Beta blocker. Constrictive pericarditis-use in Atrial fibrillation -See BHF Hypertrophic cardiomyopathies Sick sinus syndrome Recent myocardial infarction Thyroid disease (can affect pharmacokinetics of digoxin) Reduce dose in the elderly and in renal impairment Care in hypokalaemia, hypercalcaemia, hypomagnesemia and hypoxia (risk of digoxin toxicity care with high doses of diuretics) Severe respiratory disease (increased sensitivity to digoxin) Acute kidney injury monitor pulse and U&Es carefully may need withholding or dose reduction. Seek specialist advice before initiation: All patients must be discussed with Consultant Cardiologist

35 Important Interactions (see BNF for full information): Amiodarone and dronedarone will cause a gradual increase in digoxin levels. (Half dose of digoxin and check serum concentration hours later; once amiodarone dose stable check Digoxin concentration 1-2 weeks later) Calcium channel blockers plasma concentration of digoxin increased by diltiazem, verapamil and nifedipine Colchicine possible increased risk of myopathy Erythromycin, clarithromycin and other macrolides will cause a rapid increase in digoxin levels and an alternative should be found. St John s Wort reduces plasma concentration of digoxin - avoid Digoxin induced arrhythmias common in hypokalaemic patients. Monitor blood chemistry closely. Check ECG. Beta-blocker - increased risk of AV block and bradycardia Potential side effects: Usually associated with excessive dosage: anorexia, nausea, vomiting, diarrhoea, abdominal pain, visual disturbances, headache, fatigue, drowsiness, confusion, delirium, hallucinations, depression, arrhythmias, heart block, rash, intestinal ischaemia, gynaecomastia, thrombocytopenia. Arrhythmias and conduction disturbance. Patient Advice: Explain the known benefits of digoxin therapy. Warn of possible side effects. Encourage the patient not to discontinue medication without seeking medical advice. Monitoring: Watch for signs of toxicity - anorexia, nausea and vomiting, xanthopsia (yellow tint to vision), bradycardia, ventricular arrhythmias and fatigue. In elderly patients the symptoms and signs may be less specific but may include confusion and deteriorating mobility and falls. Managing adverse effects and worsening symptoms Digoxin toxicity can arise with any dose of digoxin. If digoxin toxicity is suspected withhold dose and check levels. An urgent serum digoxin concentration should be measured along with electrolyte and renal function and advice from appropriate physician sought. Excessive Bradycardia If occurs with concomitant beta blockers and digoxin therapy, digoxin should be stopped IVABRADINE IN HEART FAILURE Ivabradine is classified as Amber on the BNSSG formulary and therefore patients who may benefit from treatment can have their prescription supplied by specialist nurse NMP. However, the agreement for this must be decided with Consultant Cardiologist. See BNSSG Shared Care Protocol for Ivabradine (accessed from for further advice and monitoring.