Black Country and West Birmingham STP

Cardiovascular Disease Pathway

Approved for use in Walsall: October 2019Review Date: October 2022

Cardiovascular Disease Management Pathway

(Please note: This guideline does not cover management of PVD)

Cardiovascular Risk Assessment

Myocardial Infarction Acute Coronary Syndrome Angioplasty (see Black country STP guideline)

Angina

IHD/CHD

Heart Failure

• Diagnosis of Heart Failure

• Overview of Pharmacological management of Heart Failure

• Prescribing LOOP DIURETICS in heart failure (all heart failure patients)

• Prescribing ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACE-I) in patients with LVSD/HFrEF (LVEF≤40%)

• Prescribing BETA BLOCKERS (BB) in patients with LVSD/HFrEF (LVEF≤40%)

• Prescribing ANGIOTENSIN-II RECEPTOR BLOCKERS (ARB) for patients with LVSD/HFrEF (LVEF≤40%)

• Prescribing MINERALOCORTICOID RECEPTOR ANTAGONISTS (MRA)/ALDOSTERONE ANTAGONISTS (AA) in patients with LVSD/HFrEF (LVEF≤40%)

Stroke (anticoagulation and dual antiplatelet therapy refer to Black Country and West Birmingham STP guidelines)

Hypertension (see Black Country and West Birmingham STP hypertension guidelines)

Lipid management (see individual CCG guidelines – no Black Country and West Birmingham STP lipid management guidelines)

Scope of Guidance Introduction

• This pathway is intended to provide information on the management of people with cardiovascular conditions to reduce their risks and to identify, prevent or delay the progression of associated co-morbid vascular and metabolic conditions.

• It is also intended to identify people who are deemed to be at high risk of developing cardiovascular disease and promote activemanagement of these people to reduce or mitigate individual modifiable risk factors to reduce their overall level of risk.

Inclusion Criteria

• Myocardial Infarction Acute Coronary Syndrome Angioplasty

• Angina

• Peripheral Vascular Disease

• CVD risk >10%

Exclusion Criteria

The pathway should not be used for:

• Chest pain at time of appointment - Emergency 999 referral.

• N.B. A diagnosis of unstable angina in the past should not exclude patients who are now stable.

• Patients without CHD or found not to be at high risk of CHD following

• Risk assessment i.e. CVD risk < 10%

CV Risk StratificationAll patients who are identified as having a CVD risk of 10%, using a risk assessment tool should be added to the practice high risk of developing CVD register. These patients should then receive annual review for 5 years to enable reduction of risk

Offer atorvastatin 20 mg a day (unless contraindicated) for the primary prevention of cardiovascular disease (CVD) to people with an estimated CVD risk of 10% or more using the QRISK®2 assessment tool .Limitations of QRISK2 – underestimate risk in younger people and females – short term risk communicated onlyConsider JBS3 heart age calculator (which is not currently programmed into EMIS for the Dudley Health economy)

Consider delaying treatment if the person is committed to lifestyle interventions likely to reduce CVD risk to below 10%. Reassess CVD risk at an agreed later date.Ensure the decision to start drug treatment has been made after an informed discussion with the person about the risks and benefits of statin treatment, taking into account additional factors such as comorbidities, potential benefits from lifestyle interventions, the person's preferences, polypharmacy, general frailty and life expectancy.Take baseline blood tests. For details of this and other aspects of lipid modification treatments, see Dudley Lipid guidelinesFor people aged 85 years or older (beyond the QRISK®2 range for inclusion) consider atorvastatin 20 mg which may be of benefit in reducing the risk of non-fatal myocardial infarction. But, take into account factors that may make treatment inappropriate such as comorbidities, polypharmacy, general frailty, and life expectancy.Age is a strong independent risk factor for cardiovascular disease, older age should not be reason to withhold lipid lowering therapies – need to review on a patient by patient basis and assess individual need.

Offer antihypertensive drug treatment for the primary prevention of CVD, if appropriate: For more information on when antihypertensive drug treatment is appropriate, see the Dudley Hypertension guidelines which covers hypertension.For risk prediction in those without a pre-existing vascular diagnosis the use of an assessment tool is required. The tool given in this pathway to calculate CVD risk is QRISK2

QRISK®3 includes more factors than QRISK®2 to help enable doctors to identify those at most risk of heart disease and stroke.These are a measure of systolic blood pressure variabilityChronic kidney disease, which now includes stage 3 CKD Migraine Corticosteroids Systemic lupus erythematosus (SLE) atypical antipsychotics severe mental illness erectile dysfunction QRISK3 risk assessment tool is accessible at https://qrisk.org/three/

The QRISK®2 calculator is available on practice system software in all practices by Dudley CCG. Over the coming years the QRISK®3 calculator will be incorporated into GP clinical systems in Dudley.

Exclusions from Risk EstimationsThe following are already deemed to have high risk of CVD status conferred by pre- existing vascular diagnoses and therefore risk calculation is not required:•People with CVD•People with type 1 or type 2 diabetes aged >40 years

•People with type 1 or type 2 diabetes aged 18-39 years who have been diagnosed with one or more of the following:• retinopathy• nephropathy, including persistent microalbuminuria persistent poor glycaemic control (HbA1c >9%)• Elevated blood pressure requiring antihypertensive therapy• total serum cholesterol ≥6mmol/l• features of metabolic syndrome (central obesity and fasting triglycerides• >1.7mmol/l (non fasting >2.0mmol/l) and/or HDL cholesterol <1.0mmol/l in men or <1.2mmol/l in womenfamily history of premature CVD in a first degree relative•People with an elevated single risk factor/s, e.g. total cholesterol >6.0mmol/l.These people should be considered for lipid lowering therapy without formal risk calculation. Risk in these cases will be underestimated when using any CVD risk assessment tool.For further information on the assessment of CVD risk see the NHS Dudley Health Check Pathway and Dudley Hyperlipidaemia guideline

Screening for Transient Ischaemic Attack, Diabetes, CKD and Peripheral Arterial Disease

Diabetes Screen

A fasting plasma glucose request should be included in the blood tests required for annual review. Any fasting result of 6.1 mmol/l should be managed according to the Dudley Diabetes Management Guidelines for Adults with Type 2 Diabetes.

Transient Ischaemic Attack (TIA) Screen

TIA is defined as transient episode of focal neurological dysfunction. Focal symptoms include:

Hemiparesis, hemisensory loss

Visual symptoms such as unilateral blindness or diplopia Aphasia, dysphasia

Dysarthria, Ataxia

Asphyxia

The symptoms typically show a sudden onset and rapid resolution. For patients experiencing a TIA:

5% will have a stroke within 48 hours

10% will have a stroke within one week.

20% will have a stroke within one month.

The FAST test is a simple way of assessing suspected anterior circulation strokes, and can be used by the general public. This is being publicised locally and nationally, and the public are advised to dial 999 if they suspect they

or someone they know has had a stroke/TIA. Any of the following symptoms should prompt attention:

F Facial weakness

A Arm (and/or leg) weakness

S Speech Problems

T Time to call 999

Give patient information on the FAST test and answer any questions.

•Where TIA/ previous TIA is suspected, refer to acute services using the TIA referral form in the Stroke/TIA pathway.

•Calculate the ABCD2 score to assist appropriate referral by determination of the level of risk using the Rapid Access TIA referral form. High risk patients will be seen by acute services within 24 hours, therefore the date and time

of the event must be completed along with patient contact details – telephone number etc.

Record on the clinical system using Read code – G65%

Chronic Kidney Disease Screen

A request for urea and electrolytes should be included in the blood test requests for annual review. Estimated glomerular filtration rate (eGFR) is calculated by the pathology dept. from serum creatinine results. An eGFR result of

< 90mls/min/1.75m2 should be managed according to the NICE Chronic Kidney Disease Pathway.

Peripheral Arterial Disease Screen (Lower limb)

The annual review should include an assessment for possible peripheral arterial disease.

Symptoms

Any report of claudication of the calf muscles, thigh or buttock when walking a particular distance, which resolves on resting for approximately 5 minutes and is reproducible, should prompt investigation.

Note the distance typically walked before claudication pain is experienced.

Signs

Muscle atrophy

Loss of hair to the extremity

Thickened toe nails

Examination

Peripheral pulse palpation up to the abdominal aorta, noting for absence and/or bruits – USS Doppler to confirm

Measurement of segmental and ankle brachial pressures, comparison to the ankle brachial pressure index (ABI)

For the management of peripheral arterial disease or suspected peripheral arterial disease see NICE CG147: Lower Limb Peripheral Arterial Disease

Medical Management of Ischaemic Heart Disease

Stable anginaStable angina is pain or constricting discomfort that typically occurs in the front of the chest (but may radiate to the neck, shoulders, jaw or arms) and is broughton by physical exertion or emotional stress. Some people can have atypical symptoms, such as gastrointestinal discomfort, breathlessness or nausea. Angina isthe main symptom of myocardial ischaemia and is usually caused by atherosclerotic obstructive coronary artery disease restricting blood flow and thereforeoxygen delivery to the heart muscle.

Monitoring stable anginaAssess for:Unstable angina / ACS (STEMI/NSTEACS)There are no identifiable triggers or pattern to the chest pain and it can happen when the heart is resting. Symptoms are more severe and pain tends to last

longer. Chest pain lasts for at least 15 minutes and can be felt in the arms back or jaw. There may be nausea and/or vomiting, sweating or breathlessness or any combination of the above.ACS is inclusive of UA, NSTEMI and STEMI

Treatment • Offer a short acting nitrate e.g. sublingual GTN spray and either a beta blocker (first line: Bisoprolol 1.25mg daily) or calcium channel blocker (Amlodipine

5mg daily) as first line therapy• If beta blockers are not tolerated /contraindicated consider a calcium channel blocker and vice-versa.• If beta blockers and calcium channel blockers are not tolerated / contraindicated, consider long acting nitrate monotherapy e.g Isosorbide mononitrate • If symptom control not achieved, consider adding a long acting nitrate e.g. Isosorbide Mononitrate 30-60mg daily

Ischaemic Heart Disease (For treatment of NSTEACS and STEACS – see Black Country STP guidance)

The guidance does NOT override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.

Angina is the main symptom of myocardial ischaemia and is usually caused by atherosclerotic obstructive coronary artery disease restricting blood flow and therefore oxygen delivery to the heart muscle.

Management

The aim of management is to stop or minimise symptoms, and to improve quality of life and long-term morbidity and mortality. Management options include lifestyle advice, drug treatment and revascularisation using percutaneous or surgical techniques. Overarching Principles of Management 1. Explore and address issues according to the person's needs, which may include: • Self-management skills such as pacing their activities and goal setting • Concerns about the impact of stress, anxiety or depression on angina • Advice about physical exertion including sexual activity 2. Offer a short-acting nitrate for preventing and treating episodes of angina 3. Offer people optimal drug treatment for the initial management of stable angina. Optimal drug treatment consists of one or two anti-anginal drugs as necessary plus drugs for secondary prevention of

cardiovascular disease. 4. Offer either a beta blocker or a calcium channel blocker as first-line treatment for stable angina. • Do not routinely offer other anti-anginal drugs as first-line treatment for stable angina • Review the person's response to treatment, including any side effects, 2–4 weeks after starting or changing drug treatment 5. Consider revascularisation (coronary artery bypass graft [CABG] or percutaneous coronary intervention [PCI]) for people with stable angina whose symptoms are not satisfactorily controlled with optimal

medical treatment 6. Offer aspirin dispersible 75 mg daily for people with stable angina taking into account the risk of bleeding and comorbidities.

7. Offer statin treatment in line with Dudley hyperlipidaemia guidelines8. Offer treatment for high blood pressure in line with Dudley hypertension guidelines9. Consider angiotensin-converting enzyme (ACE) inhibitors for people with stable angina and diabetes. Offer or continue ACE inhibitors for other conditions, in line with relevant NICE guidance. 10. Do not: • Exclude people from treatment based on their age alone • Investigate or treat symptoms differently based on gender or ethnic group • Offer vitamins or fish oil. Inform people there is no evidence that they help stable angina • Offer transcutaneous electrical nerve stimulation (TENS), enhanced external counterpulsation (EECP) or acupuncture to manage stable angina

For more information on managing stable angina, including the advice, information and support which should be offered to patients see: https://www.nice.org.uk/guidance/cg126

Optimising Prescribing for Chronic Stable Angina (IHD)

**Ivabradine: requires specialist initiation but may be useful in symptomatic patients where heart rate remains > 60bpm despite optimal dose of beta-blocker or rate controlling calcium channel blocker; or where these rate controlling agents are contra-indicated or not tolerated

***Ranolazine: requires specialist initiation but may be useful in patients where the use of other options is limited by bradycardia or hypotension

The Medicines and Healthcare products Regulatory Agency (MHRA) has issued drug safety updates for ivabradine and nicorandil

Therapies to improve prognosis: - Start aspirin dispersible 75mg daily - Start a statin and manage lipids in line with local CCG guidelines.- Manage blood pressure in line with local CCG guidelines

Therapies to prevent episodes of angina FIRST LINE: Offer a beta-blocker, such as bisoprolol 5mg daily*

Aim to increase dose to achieve a heart rate between 50-60 beats per minute (bpm) *Note: A lower starting dose maybe appropriate in specific patient groups, such as the elderly or those with hypotension

If beta-blocker contraindicated or not tolerated consider a rate-controlling calcium channel blocker (diltiazem or verapamil)

If symptoms are not satisfactorily controlled, consider adding a long-acting nitrate, nicorandil, ivabradine** or ranolazine***

If rate-controlling calcium channel blocker is contraindicated or not tolerated consider a dihydropyridine calcium channel blocker (amlodipine)

If symptoms are not satisfactorily controlled, consider adding: • a long acting nitrate or • nicorandil or • ivabradine** If dihydropyridine calcium channel blocker is contraindicated or not tolerated consider adding a long-acting nitrate, nicorandil, ivabradine** or ranolazine***

If additional anti-anginal therapy is required add a dihydropyridine calcium channel blocker, such as amlodipine 5 - 10 mg daily

If both beta-blockers and calcium channel blockers are contraindicated or not tolerated consider monotherapy with: • a long-acting nitrate or • nicorandil or • ivabradine** or • ranolazine***

Provide sublingual GTN for use as required Medical

Therapy for Management of Chronic Stable Angina (IHD)

If symptoms are not adequately controlled, consider referral for revascularisation; an additional antianginal may be added whilst awaiting cardiology review

Medical Management of Heart Failure

Diagnosis and Identification of Heart Failure Measure N-terminal pro-B-type natriuretic peptide (NT-proBNP) in people with suspected heart failure. [2018]

Evidence shows that very high levels of NT-proBNP carry a poor prognosis, refer people with suspected heart failure and an NT-proBNP level above 2,000 ng/litre

(236 pmol/litre) urgently, to have specialist assessment and transthoracic echocardiography within 2 weeks. [2018]

Refer people with suspected heart failure and an NT-proBNP level between 400 and 2,000 ng/litre (47 to 236 pmol/litre) to have specialist assessment and

transthoracic echocardiography within 6 weeks. [2018]

Be aware that: NT-proBNP level less than 400 ng/litre (47 pmol/litre) in an untreated person makes a diagnosis of heart failure less likely.

The level of serum natriuretic peptide does not differentiate between heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. [NICE 2018]

Class / Read code

Patient Symptoms

Class I (Mild)

662f.

No limitation of physical activity. Ordinary physical activity does not cause

undue fatigue, palpitation, or dyspnoea (shortness of breath).

Class II (Mild)

662g.

Slight limitation of physical activity. Comfortable at rest, but ordinary physical

activity results in fatigue, palpitation, or dyspnoea.

Class III (Moderate)

662h.

Marked limitation of physical activity. Comfortable at rest, but less than

ordinary activity causes fatigue, palpitation, or dyspnoea.

Class IV (Severe)

662i.

Unable to carry out any physical activity without discomfort. Symptoms of

cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is

increased.

Read code is G5yy9 for ‘LVSD’ or 585f for ‘echocardiogram shows left ventricular systolic dysfunction’(linked to QOF HF004 in terms of beta-blocker and ACEI for prognostic benefits in Left Ventricular Systolic Dysfunction)

If remains symptomatic seek specialist advice, consider:• Digoxin• Sacubitril/Valsartan• Ivabradine• Hydralazine + Nitrate

This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient , in consultation with the patient/carer/guardian. These guidelines are for primary care management of heart failure once a diagnosis has been made.

Manage comorbid conditions – Hypertension, IHD, Diabetes Mellitus, cardiac rehabilitation and education.

N.B: Patients require diuretics at any stage of treatment (dependent on symptoms)

HFpEF (Heart failure with preserved Ejection Fraction) left ventricular ejection fraction (LVEF) >40%

HFrEF (Heart failure with reduced ejection fraction/LVSD (left ventricular systolic dysfunction) (LVEF ) < 40%

No evidence for disease modifying therapies in HFpEFDiuretics to relieve symptoms & signs of congestion and management of co-morbidities

1st Line – Angiotensin Converting enzyme (ACE-I e.g. Ramipril) and Beta-Blocker e.g. BisoprololConsider Angiotensin II Receptor Blocker (ARB e.g. Candesartan) if intolerant to ACEI (up-titrate to maximum tolerated dose of both drugs)

If remains SYMPTOMATIC despite maximal therapy with ACEI/ARB and BB2nd line – MINERALOCORTICOID RECEPTOR ANTAGONIST (MRA) or ALDOSTERONE ANTAGONIST (AA) e.g. spironolactone/eplerenoneUp-titrate to maximum tolerated dose

Heart Failure Management

Most patients with heart failure require treatment with a loop diuretic for symptom control

Establish fluid status: Blood pressure (BP), Heart Rate (HR), Jugular Venous Pressure (JVP) and Weight

Fluid overload One or more of the following: weight ↑>1.5kg above dry weight/rapid weight gain over 2-3 days ↑ Dyspnoea/ ↑ peripheral oedema or sacral oedema/orthopnoea and/or paroxysmal nocturnal dyspnoea (PND)

DehydrationTwo or more of the following:Weight ↓ >1.5kg below dry weight over 2-3 days No symptoms of ↑dyspnoea or peripheral oedemaSymptoms of thirst, dizziness or confusion

Baseline checks: BLOODS – U&Es (Urea, Creatinine, K+, Na+) eGFR

Start Furosemide 40mg daily or increase diuretic dose (see below)

Decrease diuretic dose

Prescribing ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACE-I) in patients with LVSD/HFEF (LVEF<40%)B

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Start at LOWEST dose and titrate up (some ACE-I better than no ACE-I):• Ramipril 1.25mg daily*• LISINOPRIL 2.5-5mg daily• ENALAPRIL 2.5mg BD

*ACE-I of choice in LVSD -If already on an ACE-I switch to one licensed for LVSD (LVEF <40%)

Aim for TARGET dose or maximum tolerated dose • RAMIPRIL 5mg BD or 10mg OD• LISINOPRIL 30-35mg daily• ENALAPRIL 10-20mg BD

• Double the dose at 2-4 weekly intervals-see suggested up-titration schedule• repeat baseline checks in 1-2 weeks of initiation and before/after dose changes

Bloods – U&Es (Ur, Cr, K+, Na+), eGFRBPReview other medications such as NSAIDs/nephrotoxics drugs/diuretics/ K+ sparing diureticsStop K+ supplements.Counsel on “sick day guidance” – where appropriate (see Dudley Sick Day guidance)

Suggested up-titration schedule

DRUG/Week WEEK 0-2 Week 2-4 Week 4-6 Week 6-8 Week 8-12

RAMIPRIL 1.25mg OD 1.25mg BD 2.5mg BD 5mg BD

LISINOPRIL 2.5mg OD 5mg OD 10mg OD 20mg OD 30-35mg OD

ENALAPRIL 2.5mg BD 5mg BD 10mg BD 20mg BD

In stable Heart Failure, 6 monthly U&Es

But more frequent monitoring may be required if patient is on combined loop and thiazide diuretic or MRA/AA or when there are concerns regarding the person’s clinical condition or comorbidities

ACE-I should be offered to all patients with LVSD (LVEF<40%) – see contraindications in later slide

Prescribing Beta Blockers in patients with LVSD/HFrEV (LVEF <40%)(read code G5yy9 or 585f)

BB should be offered to all patients with LVSD (LVEF<40%)DO NOT START Beta Blocker IF there are SIGNS OF FLUID overload

• HR• BP• Absence of fluid overload• ECG if HR <60bpm

Patient Information• May take weeks/months to notice benefit• Expect temporary fatigue/SOB• Self weigh daily report >1.5kg over 3-4 days increase in symptoms of fluid overload• DO NOT STOP SUDDENLY WITHOUT CARDIOLOGY ADVICE

Ensure patient stableStart at lowest dose and titrate as tolerated to achieve HR of 50-60 bpm, if in sinus rhythm or 70-80bpm if patient has AF- Bisoprolol 1.25mg daily- Carvedilol 3.125mg twice daily

Increase every 2-4 weeks to achieve target or maximum tolerated dose Repeat baseline checks before each dose change

NOTE: IF BB HAS BEEN STOPPED FOR MORE THAN 2 WEEKS , RE-INTRODUCE CAUTIOUSLY. CONSIDER STARTING FROM INITIATION DOSE

STABLE DOSE – 6 MONTHLY REVIEW

Drug Week 0-2 Week 2-4 Week 4-6 Week 6-8 Week 8-10 Week 10-12

Bisoprolol 1.25mg daily 2.5mg daily 3.75mg daily 5mg daily 7.5mg daily 10mg OD

Carvedilol 1.125mg BD 6.25mg BD 12.5mg BD 25mg BD* 50mg BD**

Nebivolol*** 1.25mg daily 2.5mg daily 5mg daily 10mg daily

*Maximum dose in patients with severe heart failure or those <85kg

**Maximum dose for bodyweight >85kg

*** Note: Nebivolol is not available as a 2.5mg tablet (needs to be halved for administration)

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Note: BB should not be stopped abruptly unless necessary due to possible rebound effects (increase risk of Myocardial ischaemia/infarction and arrhythmiaBB LICENSED FOR LVSD:1st Line: preferred agent in Dudley CCG: Bisoprolol2nd Line: more effective in reducing Blood Pressure: Carvedilol3rd Line: consider for patients over 70 years: Nebivolol

Prescribing ANGIOTENSIN – II RECEPTOR BLOCKERS (ARB) FOR PATIENTS WITH LVSD/HFReF (LVEF<40%)

N.B ARBs should be used ‘second line’ in patients with LVSD (LVEF<40%) who are intolerant or ACE-I

BASELINE INITIATION UP-TITRATION MONITORING

• BLOODS – U&Es (Ur, Cr, K+, Na+,, eGFR

• BP

Start at lowest dose and titrate up - Candesartan 2mg daily- Losartan 25mg daily- Valsartan 40mg BD

Review other medications such as NSAIDs/nephrotoxic drugs/ diuretics/K+ sparing diuretics etc.Stop K+ supplements

Aim for TARGET dose or Maximum Tolerated Dose Double dose at 2-4 weekly intervals- Candesartan 32mg daily- Losartan 150mg daily- Valsartan 160mg twice daily (max. dose 80mg daily if

mild/moderate hepatic impairment without cholestasis)

SEE SUGGESTED UP-TITRATION SCHEDULE- Repeat baseline checks within 1-2 weeks of initiation

and before/after any dose changes - More frequent monitoring may be required if patient is

on combined loop and thiazide diuretic or MRA/AA.

SUGGESTED UP-TITRATION SCHEDULESome ARB is better than no ARBARB licensed for LVSD1st Line: preferred agent in Dudley: CANDESARTAN Note: Losartan has evidence in HF at doses >100mg daily 2nd Line: LOSARTAN 3rd Line: VALSARTANIf already on an ARB switch to one licensed for LVSD

Drug/week Week 0-2 Week 2-4 Week 4-6 Week 6-8 Week 8-10

CANDESARTAN 4mg daily 8MG DAILY 16mg daily 32mg daily

LOSARTAN 12.5mg daily 25mg daily 50mg daily 100mg daily 150mg daily

VALSARTAN 40mg BD 80mg BD 160mg BD

6 monthly review

Suggested up-titration schedule

CONTRAINDICATIONS

•History of hypersensitivity to ARB or any excipients •Pregnancy and breastfeeding •Severe hepatic impairment and/or cholestasis; biliary cirrhosis •Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption •Patient on both an ACE-I and MRA/AA •Baseline serum K+> 5.5 mmol/L CAUTIONS •Symptomatic or severe asymptomatic hypotension (systolic BP <90 mmHg) •Moderate to severe renal impairment i.e. serum creatinine >150 micromol/L or eGFR < 50 ml/min. See individual SPCs for dose adjustment requirements •Patients with volume depletion such as those on high dose diuretics may lead to symptomatic hypotension therefore volume should be restored prior to administration •Bilateral renal artery stenosis, or renal artery stenosis in a single functioning kidney •Patients on haemodialysis •Kidney transplant recipients •Hepatic impairment •Haemodynamically relevant aortic or mitral valve stenosis •Hypertrophic cardiomyopathy •Primary aldosteronism •Patients taking potassium supplements or other drugs that may increase potassium •Baseline serum K+ between 5 to 5.5 mmol/L •Drug interactions – see BNF for list Seek specialist advice prior to initiation: •Concomitant therapy with an ACE-I – The triple combination of an ACE-I, ARB, and an MRA/AA or other potassium-sparing diuretic is not recommended due to the risk of adverse events, especially renal impairment and hyperkalaemia. Further checks of blood chemistry should be made every 4 weeks for 3 months and then 3 monthly for one year and then at least 6 monthly, but more frequently if clinically indicated. •Suspected or confirmed aortic or mitral valve disease •Primary aldosteronism •Hypertrophic cardiomyopathy •Hyponatraemia (serum Na+ <135 mmol/L) •Symptomatic or severe asymptomatic hypotension (systolic BP<90 mmHg) •Significant renal dysfunction / renovascular disease e.g. creatinine > 150 micromol/L or eGFR<50 ml/min or hyperkalaemia (serum K+ >5.0 mmol/L) •Renovascular disease (diagnosed, undiagnosed

BOX 1: FOR IMPORTANT INFORMATION AND CONTRAINDICATIONS ARBs have a more limited evidence base than ACE-I and have not shown superiority over ACE-I in any large robust clinical trial. There are currently no compelling indications for the use of ARBs routinely first line in HF. ARBs should only be considered second line in patients intolerant to ACE-I.

•Angioedema: Rare but life threatening. Discontinue therapy and seek urgent medical advice. •Asymptomatic hypotension: Does not usually warrant a change in therapy. Do not increase dose if systolic BP < 90 mmHg •Symptomatic hypotension: Consider dehydration and address as appropriate - review diuretic dose with a view to decreasing dose if patient free of symptoms suggestive of fluid retention If dizziness, light-headedness and/or confusion occur in the setting of low BP, reduce dose of ARB (back to last tolerated dose), and review use of other vasodilators (e.g. nitrates, CCB). Monitor closely and allow longer intervals between dose titrations Aim to maintain treatment with both ARB and beta-blockers, at a reduced dose if necessary Seek specialist advice if measures do not resolve symptomatic hypotension •Worsening renal function: An increase in serum urea, creatinine and K+ is to be expected after initiation/titration of ARB. If the increase is small and asymptomatic, no action is necessary. See BOX 3 for recommended actions.

Blood Chemistry Action

Creatinine ↑ up to 50% above baseline or to 265 micromol/L

(whichever is smaller). OR serum K+ ↑ to ≤5.5 mmol/L

No urgent action required. Repeat blood chemistry (urea, creatinine

and K+) within 2-4 weeks

Creatinine ↑ > 50% but < 100% above baseline or between 265

micromol/L and 310 micromol/L (whichever is smaller).

OR serum K+ ↑ to ≥ 5.5 - ≤5.9 mmol/L

Review required- consider: a. Stopping concomitant nephrotoxic

drugs e.g. NSAIDs, non essential vasodilators (e.g. calcium

antagonists, nitrates) and if no signs of fluid retention, reduce the

dose of diuretic. b. Review causes of high potassium. Stop other

agents that cause hyperkalaemia e.g. potassium sparing diuretics, or

dietary intake. Recheck renal function within 2 weeks. If despite

adjusting medication the creatinine and K+ remain higher than above

the dose of ARB should be halved or stopped if at initiation dose and

the blood chemistry re-checked in 5-7days. If the response to this is

not satisfactory, seek specialist advice. Blood chemistry should be

monitored closely until K+ and Creatinine concentrations are stable

Creatinine ↑ by >100% (from baseline) or to above 310 micromol/L

OR serum K+ ≥ 6 mmol/L

Discontinue ARB and discuss with cardiologist Note: It is very rarely

necessary to stop an ARB and in patients with heart failure clinical

deterioration is likely if treatment is withdrawn; in this instance

specialist advice should be sought before treatment discontinuation.

BOX 3: ACTION TO TAKE IN WORSENING RENAL FUNCTION

Prescribing MINERALOCORTICOID RECEPTOR ANTAGONISTS (MRA/ALDOSTERONE ANTAGONISTS (AA) in patients with LVSD/HFrEF (LVEF < 40%)

IMPORTANT INFORMATION AND CONTRAINDICATIONS

MRA/AA in addition to optimal ACE-I and BB therapy, have been proven to reduce mortality and hospitalisation in selected patentswith heart failure due to LVSD.

CONRAINDICATIONS• Anuria• Acute renal impairment (Baseline serum creatinine >200micromol/L or eGFR <30ml/min)• Hyperkalaemia (serum K+ >5.0 mmol/L) at initiation • Addison’s Disease• Hypersensitivity to specific AA?MMRA or excipients • Hyponatraemia a(serum Na+ <135mmol/L)• Co-prescription of potassium sparing diuretics, potassium supplements• Co-prescribing epleronone with strong CYP3A4 enzyme inhibitors – see Box 2 for common drug interactions • Severe Hepatic Impairment (Childs Pugh Class C)• In addition to the combination of both an ACE and an A

CAUTIONS• Porphyria• Pregnancy and lactation • Hepatic impairment (child Pugh class A&B, monitor electrolytes closely)• Moderate to severe renal impairment (Cr>150 micromole/L or eGFR <50ml/min)• Diabetic microalbuminuria• Elderly – monitor K+ closely• Consider drug/food interactions

Specialist cardiologist advice recommended for:Hyponatraemia (serum Na+ <135 consider stopping and seek specialist cardiologist advice Pregnancy/lactationSymptomatic hypotension or severe asymptomatic hypotension (systolic BP<90mmHg)Significant renal dysfunction/renovascular disease e.g. creatinine >150 micromole/L or EGFR <50ml/min or hyperkalaemia

Adverse Effects• Sodium/water depletion/hypovolaemia – consider reduction in diuretic dose e.g. bumetanide or furosemide. Recheck U&Es

consider reducing the dose or stopping.• Symptomatic hypotension- measure blood biochemistry. Assess fluid intake – consider a reduction in diuretic dose or omit 1 or

2 days of therapy – advise patient to avoid abrupt postural changes – review if symptoms persist – seek specialist advice • GI Upset - reduce dose/discontinue• Hyponatraemia – serum Na+ <135mmol/L consider stopping and seek medical advice • Gynaecomastia – can occur as a side effect of spironolactone –epleronone can be considered as a suitable alternative where

patients do not tolerate spironolactone.

Interacting Drug Mechanism of Action

ACEI/ARB/Aliskiren Increased risk of hyperkalaemia. Monitor serum potassium closely if

combination therapy is used. Combination of SCE/ARB and MRA/AA are

contraindicated

Cardiac Glycosides May increase digoxin levels. Monitor for signs of digoxin toxicity. Dose

adjustment may be required.

Ciclosporin/tacrolimus Risk of hyperkalaemia and renal dysfunction. Concurrent use to be avoided, if

concurrent use is essential monitor K+ and renal function

Glucocorticoid and tetracosactide May precipitate sodium and fluid retention – monitor carefully

NSAIDs Caution with combination use, patients must be well hydrated and have

regular renal function tests.

Potassium and other potassium sparing Increased risk of hyperkalaemia – monitor serum K+

Tricyclics, antidepressants, neuroleptics, amifostine,

baclofen

Co-administration of these drugs with epleronone may potentially increase

antihypertensive effects and increase the risk of postural hypotension

Trimethoprim Increased risks of hyperkalaemia. Monitor those with impaired renal function

an elderly closely

Strong CYP3A4 inhibitors e.g. ketoconazole, itraconazole,

ritonavir, melfinavir, clarithromycin, telithromycin and

nefazodone

Risk of increased plasma concentration of epleronone. Maximum dose of

25mg epleronone.

Mild to moderate CYP3A4 inhibitors: erythromycin,

saquanivir, amiodarone, diltiazem, verapamil and

fluconazole

Risk of increased plasma concentration of epleronone. Maximum dose 35mg

of epleronone.

CYP3A4 inducers – rifampicin, carbamazepine,

phenytoin, phenobarbital, St John’s Wort

Risk of decreased epleronone effects – concomitant use is not recommended

Hypertension

http://www.dudleyformulary.nhs.uk/page/20/guidelines for further information on hypertension pathway or NICE guidelines for National guidance.

Black Country STP – Hypertension Guidelines (Treatment Summary)

If BP remains uncontrolled with either optimal or maximum tolerated doses of four drugs, check adherence and seek expert advice if not already obtained

MonitoringACEI / ARB: Check baseline renal profile; recheck within 2 weeks of initiation or dose increase and then at least annually. If serum creatinine increases by >20% (or eGFR falls by < 15%) after initiation –stop ACEI and seek specialist advice. ACEI dose should only be increased if serum creatinine increases by less than 20% (or eGFR falls by less than 15%) after each dose titration, potassium < 5.5mmol.

Common side effects: Dry cough (consider ARB such as candesartan), rash.

Calcium Channel blocker: Common side effects: Flushing and headaches at initiation, swollen ankles especially at higher dose. Amlodipine interacts with simvastatin – where statin indicated use maximum simvastatin 20mg daily in combination or consider atorvastatin. Thiazide-type diuretic: Check baseline renal profile; recheck within 2 weeks of initiation and then at least annually. If serum potassium falls below 3.5mmol/L or eGFR to <25 refer to GP for advice. Likely to increase urine output

http://www.dudleyformulary.nhs.uk/page/20/guidelines for further information on lipid management

Hyperlipidaemia

ACE-I Angiotensin Converting Enzyme Inhibitor AF Atrial Fibrillation ARB Angiotensin II Receptor Blocker AA Aldosterone Antagonist BB Beta Blocker BD Twice Daily BM Blood glucose Monitoring BNF British National Formulary BP Blood Pressure BPM Beats Per Minute CCB Calcium Channel Blocker COPD Chronic Obstructive Pulmonary Disease Cr Creatinine DM Diabetes Mellitus ECG Electrocardiogram eGFR estimated Glomerular Filtration Rate EMIS Egton Medical Information System GP General Practitioner HF Heart Failure HFNS Heart Failure Nurse Specialist HFpEF Heart Failure with preserved Ejection Fraction HFrEF Heart Failure with reduced Ejection Fraction HTN Hypertension HR Heart Rate IDDM Insulin Dependent Diabetes Mellitus IHD Ischaemic Heart Disease

IV Intravenous K+ Potassium Kg Kilogram LFT Liver Function Test LVEF Left Ventricular Ejection Fraction LVSD Left Ventricular Systolic Dysfunction Micromol/L Micromole per Litre Mg Milligram mmHg Millimetres of mercury mmol/L Millimoles per litre ml/min Millilitres per minute MRA Mineralocorticoid Receptor Blocker Na+ Sodium NICE National Institute for Clinical Excellence NSAIDs Non-Steroidal Anti-Inflammatory Drugs OD Once Daily OTC Over The Counter PND Paroxysmal Nocturnal Dyspnoea PVD Peripheral Vascular DiseaseSR Sinus Rhythm SPC Summary of Product Characteristics Ur Urea U&Es Urea and Electrolytes

1. National Institute for Health and Care Excellence 2010. Chronic Heart Failure in adults: Management. Clinical Guideline 108. Available at : https://www.nice.org.uk/guidance/cg108

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