Previous changes

April 2026 — minor update. Updated the recommendation for alternative first-line management of heart failure with reduced ejection fraction to angiotensin receptor-neprilysin inhibitors (ARNIs).

March 2026 — minor update. Typographical error corrected.

September 2025 — minor update. Updated management and prescribing recommendations in line with the NICE guideline Chronic heart failure in adults: diagnosis and management (2025), including prescribing information for angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). Added prescribing information sections for mineralocorticoid receptor antagonists (MRAs) and ARNIs. 

May 2025 — minor update. Updated QOF indicators in line with the NHS England Quality and Outcomes Framework guidance for 2025/26.

February 2025 — minor update. Added intestinal angioedema as an adverse effect of candesartan, in line with the manufacturer's Summary of Product Characteristics (SPC).

August 2024 — minor update. Updated wording on monitoring estimated glomerular filtration rate (eGFR) and creatinine after initiating or titrating renin–angiotensin system antagonists.

May 2024 — minor update. Clarified advice on fluid restriction for people with severe symptomatic heart failure and signs of fluid overload.

March 2024 — minor update. Added genital infections as an adverse effect of dapagliflozin, in line with the manufacturer's SPC.

January 2024 — minor update. Typographical error corrected. Added reference to the furosemide SPC.

October 2023 — minor update. Clarified recommendations in the management sections.

July 2023 — minor update. Added information that dapagliflozin is recommended by NICE as an option for treating symptomatic chronic heart failure with preserved or mildly reduced ejection fraction.

June 2023 — minor update. Added information that dapagliflozin is an option for treating symptomatic chronic heart failure with preserved or mildly reduced ejection fraction, on the advice of a heart failure specialist, in line with the NICE technology appraisal Dapagliflozin for treating chronic heart failure with preserved or mildly reduced ejection fraction. Also made minor structural changes to the prescribing information section.

January 2023 — minor update. Updated the quality standards in line with the revised NICE Quality standard Chronic heart failure in adults [QS9].

November 2022 — minor update. Added information advising that concomitant use of losartan and grapefruit juice should be avoided, as grapefruit juice decreases its therapeutic effect.

September 2022 — minor update. Added information on the use of empagliflozin for treating chronic heart failure with reduced ejection fraction. Also added a prescribing section on managing sodium-glucose cotransporter-2 (SGLT2) inhibitor.

July 2022 — minor update. Clarified prognostic information on lymphocytes. Also added information on platelet to lymphocyte ratio and poorer prognostic outcome. 

February 2022 — reviewed. A literature search was conducted in January 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. 

August 2021 — minor update. Added advice to include iron studies as part of the assessment of people with heart failure and to manage comorbid hypertension, based on the European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic heart failure.

May 2020 – minor update. Added prescribing information in response to the NICE COVID-19 rapid evidence summary: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in people with or at risk of COVID-19.

August 2019 — minor update. Updated the topic in line with the NICE guideline Chronic heart failure in adults: diagnosis and management.

January 2017 — reviewed. Updated the topic to include recommendations from the Scottish Intercollegiate Guidelines Network (SIGN) guideline Management of chronic heart failure.

December 2016 — minor update. Added information on a possible interaction between ACE inhibitors and mammalian target of rapamycin (mTOR) inhibitor therapy, which may increase the risk of angioedema [ABPI, 2016].

July to November 2015 — reviewed. A literature search was conducted in November 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. Text changes include alterations to the classification of heart failure as 'heart failure with reduced ejection fraction' and 'heart failure with preserved ejection fraction'.

May 2015 — minor updates:

• Clarified the Medicines and Healthcare products Regulatory Agency (MHRA) warning regarding the concomitant use of renin-angiotensin system (RAS) blocking agents.
• Updated information on the increased risk of hyperkalaemia with concurrent use of spironolactone and nonsteroidal anti-inflammatory drugs, in line with the SPC for spironolactone.
• Added a drug interaction section for spironolactone.

December 2014 — minor updates. Removed information on cilazapril following its discontinuation.

July 2014 — two minor updates:

• Added an MHRA warning that combining different classes of RAS blocking agents is not recommended because of an increased risk of hyperkalaemia, hypotension, and renal impairment.
• Text has been updated to replace the Liverpool Care Pathway with new standards of care that have been issued by the Leadership Alliance for the Care of Dying People.

March 2014 — minor update. Updated contraindications for ivabradine to clarify that it is contraindicated only in people with acute or unstable heart failure.

December 2013 — minor update. Updated the prescribing information for perindopril in line with the SPC.

July 2013 — minor update. Updated links to the Driver and Vehicle Licensing Agency (DVLA) website.

June 2013 — minor update. Added the 2013 QOF options for local implementation.

February 2013 — minor update. Added the 2013 QIPP options for local implementation.

January 2013 — minor update. Removed the black triangle status from losartan and valsartan. Updated the recommended dose of losartan following publication of the ESC guidelines on acute and chronic heart failure.

October 2012 — minor update. Added the 2012 QIPP options for local implementation.

April 2012 — minor update. Added the 2012/2013 QOF indicators. 

February 2012 — minor update. Minor typographical error corrected in Prescribing Information. 

January 2012 — minor update. Updated prescribing information for bisoprolol to include asthenia as a common adverse effect in people with chronic heart failure, in line with the SPC.

July 2011 — minor update. Updated prescribing information for candesartan to include cough as a very rare adverse effect, in line with the SPC for Amias®. Issued in September 2011.

June 2011 — minor update. Added the 2011/2012 QOF indicators and the 2010/2011 QIPP options for local implementation. 

August to November 2010 — topic updated. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.
The topic was updated to reflect the publication of the NICE guideline Chronic heart failure: national clinical guideline for diagnosis and management in primary and secondary care. The diagnostic and management scenarios and the evidence sections have been rewritten or updated.

New evidence

Evidence-based guidelines

No changes in evidence-based guidelines since 1 May 2026.

HTAs (Health Technology Assessments)

No new HTAs since 1 May 2026.

Economic appraisals

No new economic appraisals relevant to England since 1 May 2026.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 May 2026.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 May 2026.

New policies

No new national policies or guidelines since  1 May 2026.

New safety alerts

No new safety alerts issued since  1 May 2026.

Changes in product availability

No changes in product availability since  1 May 2026.

Basis for recommendation

This information is based largely on the National Institute for Health and Care Excellence (NICE) guideline Chronic heart failure in adults: diagnosis and management [NICE, 2025b] and the European Society of Cardiology (ESC) 2026 Guidelines for the diagnosis and treatment of acute and chronic heart failure [Køber, 2026].

Interpretation of natriuretic peptide levels

• N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a serum natriuretic peptide released in response to myocardial stretch and wall stress [Myhre, 2024].
  • Serum natriuretic peptide levels support the diagnosis of heart failure but do not differentiate between heart failure with preserved, mildly reduced, and reduced ejection fraction.
  • Higher serum natriuretic peptide levels are associated with more advanced heart failure and a poorer prognosis, and rising levels may indicate worsening heart failure.
• Serum natriuretic peptide levels may be reduced in [NICE, 2025b]:
  • People living with obesity.
  • People of African or African-Caribbean ethnic background.
  • People taking any of the following: 
    • A diuretic.
    • An angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor-neprilysin inhibitor (ARNI), or angiotensin II receptor blocker (ARB).
    • A beta-blocker.
    • A mineralocorticoid receptor antagonist (MRA).
• Serum natriuretic peptide levels may be elevated in conditions other than heart failure, including [NICE, 2025b]:
  • Pulmonary disease, such as chronic obstructive pulmonary disease.
  • Renal disease.
  • Liver disease, such as cirrhosis.
  • Systemic disease.
  • Sepsis.
  • Diabetes.

Basis for recommendation

These recommendations are based largely on the National Institute for Health and Care Excellence (NICE) guideline Chronic heart failure in adults: diagnosis and management [NICE, 2025b] and the European Society of Cardiology (ESC) 2026 Guidelines for the diagnosis and treatment of acute and chronic heart failure [Køber, 2026].

• The recommendation to urgently assess pregnant or postpartum women with suspected heart failure is based on the ESC guideline, which highlights the importance of early recognition and specialist assessment of peripartum cardiomyopathy. In addition, some medicines used to treat heart failure, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), are contraindicated during pregnancy.

Basis for recommendation

This information is taken from the National Institute for Health and Care Excellence (NICE) guideline Chronic heart failure in adults: diagnosis and management [NICE, 2025b], the European Society of Cardiology (ESC) 2026 Guidelines for the diagnosis and treatment of acute and chronic heart failure [Køber, 2026].

How should I manage a person with newly diagnosed or established heart failure?

• Start (or continue) drug treatment according to the type of heart failure and the person's clinical circumstances.
  • Heart failure treatments may be initiated in primary or secondary care depending on the type of heart failure, local service arrangements, and shared care pathways. 
• Review prescribed and over-the-counter medicines and, if appropriate, reduce or stop any medicines that may cause or worsen heart failure.
• Ensure that the person has been offered a personalized, exercise-based cardiac rehabilitation programme. The programme may be incorporated within an existing cardiac rehabilitation programme and should: 
  • Follow an assessment to ensure that it is suitable for the person.
  • Be provided in a format and setting (at home, in the community, or in hospital) that is easily accessible for the person.
  • Incorporate psychological and educational components.
  • Provide information on support available from healthcare professionals during the programme.
• Identify and manage, as appropriate:
  • Underlying causes and risk factors, such as hypertension and diabetes.
  • Complications, such as chronic kidney disease and depression. 
• Consider whether antiplatelet or statin therapy is indicated, taking into account the person's cardiovascular disease and risk factors. 
  • For more information, see the CKS topics on Antiplatelet treatment, CVD risk assessment and management, and Lipid modification - CVD prevention.
• Offer a loop diuretic, such as furosemide, to relieve congestive symptoms and fluid retention. 
• Assess nutritional status.
  • If the body mass index (BMI) is under 18.5 kg/m², consider referring for dietetic advice.
  • If the BMI is over 30 kg/m², give advice on achieving a healthy weight. For more information, see the CKS topic on Obesity.
• Ensure the person has been offered an annual influenza vaccine and a once-only pneumococcal vaccination.
  • For more information, see the CKS topics on Immunizations - seasonal influenza and Immunizations - pneumococcal.
• In people with heart failure with reduced ejection fraction (HFrEF), assess iron status and check for anaemia.
  • Measure transferrin saturation (TSAT), serum ferritin, and haemoglobin.
  • Consider iron sucrose, ferric carboxymaltose, or ferric derisomaltose for people with haemoglobin less than 150 g/L if they have iron deficiency (defined as TSAT less than 20% or serum ferritin less than 100 nanograms/mL).
  • If iron deficiency anaemia is identified, consider alternative causes rather than assuming it is related to heart failure. For more information, see the CKS topic on Anaemia - iron deficiency.
• In people of childbearing potential, discuss contraception and pregnancy.
  • Advise the person to continue effective contraception until they have received pre-conception counselling from a cardiologist and an obstetrician. For further information, see the CKS topic on Contraception - assessment.
  • If pregnancy is planned or occurs, seek specialist advice.
  • Ensure people who become pregnant receive joint care from a cardiologist and an obstetrician.
• Give general information and advice on heart failure.
  • Provide a self-management plan, or review the person's existing plan.
  • If appropriate, offer a discussion about advance care planning and advance decisions. For more information, see the section on advance planning in the Scenario: End-stage heart failure and the section on important communication issues in the CKS topic on Palliative care - general issues.
• Arrange appropriate review in primary care.
  • People with heart failure should be reviewed every few days to 2 weeks following changes in clinical status or treatment, and at least every 6 months when clinically stable.

What drug treatments are recommended for people with chronic heart failure?

• Mineralocorticoid receptor antagonists and SGLT2 inhibitors are recommended for all symptomatic patients with HF, regardless of LVEF. Other agents can be used in selected patients.
• For people with heart failure with reduced ejection fraction (HFrEF):
  
  • Initial treatment should include an angiotensin-converting enzyme (ACE) inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a sodium-glucose cotransporter-2 (SGLT2) inhibitor.
    • If symptoms persist despite the maximum tolerated doses, switching from an ACE inhibitor to an angiotensin receptor-neprilysin inhibitor (ARNI) may be considered on specialist advice.
    • If an ACE inhibitor is not tolerated (other than because of angioedema), an ARNI may be used in combination with a beta-blocker, MRA, and SGLT2 inhibitor. 
    • If there is a history of ACE inhibitor-associated angioedema or an ARNI is not tolerated, an angiotensin II receptor blocker (ARB) may be considered.
    • If symptoms persist despite optimal treatment, specialist treatments may be considered, including ivabradine, hydralazine in combination with a nitrate, and digoxin.
• For people with heart failure with preserved ejection fraction (HFpEF):
  • An MRA and an SGLT2 inhibitor may be considered.

How should I follow up a person with chronic heart failure?

People with heart failure should be reviewed every few days to 2 weeks following changes in clinical status or treatment, and at least every 6 months when clinically stable.

 At each follow-up appointment:

• Review current treatments.
  • Assess adherence to heart failure treatments and ask about adverse effects.
  • Adjust diuretic doses according to symptoms and fluid status.
  • For people taking amiodarone, review for adverse effects and the need to continue treatment.
  • Review other prescribed and over-the-counter medicines and, where appropriate, reduce or stop any that may cause or worsen heart failure.
• Assess symptoms, signs, and functional status.
  
  • Ask about breathlessness, palpitations, oedema, fatigue, exercise tolerance, and syncopal or presyncopal symptoms.
    • If the person has syncope or presyncope (unless clearly due to postural hypotension), refer to a cardiologist, as this may indicate ventricular tachycardia, particularly in people with reduced ejection fraction. 
  • Check pulse rate and rhythm, and examine for heart murmurs or other abnormal heart sounds.
    • If an arrhythmia is suspected, arrange a 12-lead ECG or 24-hour ECG monitoring. For further information, see the CKS topic on Palpitations.
    • If symptoms have deteriorated and the pulse is regular, consider arranging an ECG to assess for atrial tachycardia.
  • Assess functional capacity using the New York Heart Association (NYHA) functional classification.
  • Assess fluid status by checking for:
    • Changes in body weight.
    • Oedema (abdomen, sacrum, genitalia, and ankles).
    • Raised jugular venous pressure.
    • Fine lung crepitations. 
    • Hepatomegaly.
    • Postural drop in blood pressure — a decrease in systolic blood pressure of more than 20 mmHg may indicate hypovolaemia.
• Arrange appropriate blood tests.
  • Check renal function, iron status, and haemoglobin at every clinical review.
  • For people taking amiodarone, offer liver and thyroid function tests.
• Review comorbidities and wider health needs.
  • Assess cognitive function and psychosocial wellbeing, including symptoms of anxiety and depression. For further information, see the CKS topics on Generalized anxiety disorder and Depression.
  • Assess nutritional status.
    • If the body mass index (BMI) is under 18.5 kg/m², consider referring for dietetic advice.
    • If the BMI is over 30 kg/m², give advice on achieving a healthy weight. For more information, see the CKS topic on Obesity.
• Review ongoing management.
  • Check that the person has been offered, or has completed, a personalized, exercise-based cardiac rehabilitation programme. 
  • Ensure immunizations are up to date.
  • Review contraception and pregnancy advice where relevant.
  • Provide a self-management plan, or review the person's existing plan.
  • Ensure the person and their carers or family have access to appropriate information and advice.
• Refer for specialist review if symptoms persist despite optimal treatment or if management is complicated by comorbidities or adverse effects.
  • Specialist treatment options may include:
    
    • Pharmacological treatment, such as ivabradine, digoxin, or hydralazine in combination with a nitrate.
    • Cardiac resynchronization therapy or an implantable cardioverter-defibrillator (ICD).
    • Cardiac transplantation for severe refractory symptoms or refractory cardiogenic shock.
  • Specialists may consider measuring NT-proBNP as part of treatment optimization in people aged under 75 years with heart failure with reduced ejection fraction and an estimated glomerular filtration rate (eGFR) greater than 60 mL/min/1.73 m².

What information and advice should I give to a person with chronic heart failure?

• Provide information on heart failure, including the nature of the condition, the importance of treatment adherence, and the need for regular follow-up.
  • Useful sources of information include:
    • NHS A-Z — www.nhs.uk. 
    • British Heart Foundation — Living with heart failure.
    • European Society of Cardiology — Heart failure matters.
    • British Society for Heart Failure — http://www.bsh.org.uk.
• Provide safety-netting and self-management advice:
  • Explain the symptoms and signs of worsening heart failure, including increasing breathlessness, fatigue, ankle or abdominal swelling, and rapid weight gain. 
    • Advise the person to seek medical advice if symptoms or signs of worsening heart failure develop, and urgent medical advice if symptoms are severe or deteriorate rapidly.
  • Consider home monitoring of body weight to detect fluid retention.
    • Advise weighing at the same time of day, if possible, and agree how frequently weight should be monitored.
    • Explain what action to take if there is a sudden and sustained weight gain (for example, more than 2 kg over 3 days). This may include adjusting the diuretic dose where previously agreed or seeking medical advice.
    • Explain that worsening heart failure may occur without weight gain.
  • Advise increased fluid intake during episodes of diarrhoea or vomiting to reduce the risk of dehydration.
    • Explain sick day rules, including temporarily stopping angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), diuretics, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors during dehydrating illness. The Medicine sick day guidance leaflet may be used to support this advice.
    • Advise the person to seek medical advice if diarrhoea or vomiting persists, or if heart failure becomes severe or uncontrolled, as their medication, renal function, and electrolytes may need to be reviewed.
• Provide advice on lifestyle and practical issues, including: 
  • Diet — advise the person to eat a healthy diet and maintain a healthy weight.
  • Salt and fluid restriction — do not routinely advise people with heart failure to restrict their sodium or fluid consumption.
    • Consider fluid restriction in people with dilutional hyponatraemia or severe symptomatic heart failure with fluid overload.
    • Review the need for fluid restriction regularly.
    • Advise against potassium-containing salt substitutes.
    • Advise increased fluid intake during hot weather to reduce the risk of dehydration.
  • Smoking cessation — encourage people who smoke to stop, and consider referral to smoking cessation services.
    • For more information, see the CKS topic on Smoking cessation.
  • Alcohol — advise that it is safest not to drink more than 14 units a week on a regular basis. 
    • People who drink up to 14 units per week should spread this evenly over 3 days or more.
    • People with alcohol-related heart failure should abstain from alcohol. 
    • For more information, see the CKS topic on Alcohol - problem drinking. 
  • Physical activity — encourage regular physical activity appropriate to the person's functional capacity.
    • Advise people with New York Heart Association (NYHA) class III or IV heart failure to avoid water-based exercise.
  • Sexual activity — reassure people with stable heart failure that they can usually undertake normal sexual activity provided it does not provoke symptoms.
  • Driving — advise the person to check the Driver and Vehicle Licensing Agency (DVLA) medical standards and ensure that their motor insurance remains valid.
  • Travel — explain that most people with heart failure can travel by air if clinically stable. Advise the person to:
    • Continue taking regular medicines and carry an adequate supply for the duration of the trip, together with extra medication in case of delays. 
    • Carry medicines in hand luggage when travelling by air.
    • Carry a written summary of their medical history and current medicines.
    • Maintain adequate fluid intake and avoid dehydration, particularly during flights and in hot climates. 
    • Be aware that some medicines (for example, amiodarone) may increase sensitivity to sunlight.
    • Inform the airline in advance if they require special assistance or in-flight oxygen.

When should I suspect end-stage heart failure?

• Suspect end-stage heart failure in people with advanced symptoms despite optimal treatment, recurrent decompensation, progressive functional decline, and limited treatment options.
• Common symptoms include:
  • Pain.
  • Breathlessness.
  • Persistent cough.
  • Fatigue.
  • Limitation of physical activity.
  • Depression and anxiety.
  • Constipation.
  • Loss of appetite and nausea.
  • Oedema.
  • Insomnia.
  • Cognitive impairment.
• Features that may indicate a person is approaching the end of life include:
  • Frequent hospital admissions.
  • Persistent symptoms despite optimal treatment, including severe breathlessness at rest (New York Heart Association [NYHA] class IV).
  • Cardiac cachexia.
  • Low serum albumin.
  • Progressive deterioration in estimated glomerular filtration rate (eGFR) and hypotension limiting the use of drug treatments.
  • Acute deterioration and increasingly frequent hospital admissions from comorbid conditions (such as a chest infection).
  • Poor quality of life and dependence on others for most activities of daily living.
  • Heart transplantation and mechanical circulatory support are no longer treatment-appropriate options.
  • Clinical judgement that the person is approaching the end of life.
• Do not use prognostic risk tools to determine referral to palliative care services. Referral should be guided by clinical judgement, taking into account symptom burden, functional decline, and the person's overall clinical condition.

How should I manage a person with end-stage heart failure?

• Coordinate care with the multidisciplinary team (MDT), which may include community nurses, heart failure specialist nurses, a palliative care team, occupational therapists, physiotherapists, dietitians, out-of-hours services, and hospice care.
  • Information on available resources for healthcare professionals caring for people receiving end-of-life care is available in the CKS topic on Palliative care - general issues.
• Review current treatments, including over-the-counter medicines.
  • If appropriate, reduce or stop treatments that are no longer providing symptomatic benefit or that may cause harm.
  • Liaise with a cardiologist to ensure that all appropriate treatment options have been considered, including planned deactivation of implantable cardioverter-defibrillators (ICDs), where appropriate. 
    
    • This may require an MDT decision.
    • Reassure the person and their family that ICD deactivation is not expected to result in immediate death, whereas repeated ICD shocks during the terminal phase can be distressing.
    • For patient information, see the British Heart Foundation's leaflet on Deactivating the shock function of an implantable cardioverter defibrillator towards the end of life.
• Discuss goals of care with the person and, where appropriate, their family or carers.
  
  • Explore the person's understanding of their condition.
  • Discuss prognosis sensitively and agree realistic goals of care, taking into account preferences for place of care, place of death, and resuscitation.
  • Revisit goals of care regularly, recognizing that preferences may change as the condition progresses, and that some people may choose not to, or may not be able to, express a preference (for example, because of depression or cognitive impairment).
• Assess and manage symptoms.
  • Assess symptoms regularly using clinical assessment and, where appropriate, a validated tool, such as the Numeric Rating Scale, the Edmonton Symptom Assessment Scale (ESAS or ESAS-HF), or the Integrated Palliative Care Outcome Scale.
  • Provide appropriate symptom relief, including management of:
    
    • Breathlessness — optimize standard treatment. For further information on managing breathlessness in palliative care, see the CKS topic on Palliative care - dyspnoea.
    • Pain — assess and manage the underlying cause where possible. For information on managing cardiac ischaemic pain, see the CKS topic on Angina. For generalized pain, see the CKS topic on Palliative cancer care - pain. 
    • Anxiety and depression. For more information, see the CKS topics on Generalized anxiety disorder and Depression, and the section on Assessing and managing psychological needs in the CKS topic on Palliative care - general issues. 
    • Insomnia. For more information, see the CKS topic on Insomnia.
    • Constipation, nausea, and loss of appetite. For more information, see the CKS topics on Palliative care - constipation and Palliative care - nausea and vomiting.
• Offer advance care planning.
  • An advance care plan should be reviewed regularly and may include:
    • Anticipatory prescribing and crisis planning.
    • Psychological and spiritual support.
    • Support for family and carers.
    • Discussion of prognosis.
    • Preferred place of care.
    • Cardiopulmonary resuscitation (CPR) decisions, where appropriate.
    • Communication of these decisions to out-of-hours and ambulance services.
  • Discuss advance decisions, which allow a person with capacity to specify treatments they would not want to receive if they subsequently lose capacity to make that decision. For more information on advance decisions, see the CKS topic on Dementia.

Dose, titration, and monitoring of angiotensin-converting enzyme inhibitors

• The angiotensin-converting enzyme (ACE) inhibitors licensed in the UK for the treatment of heart failure are captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, and ramipril [BNF, 2026].
  • The recommended doses are [BNF, 2026]:
    • Captopril: initially 6.25mg to 12.5 mg 2–3 times daily, increased gradually at intervals of at least 2 weeks if tolerated to a maximum of 150 mg daily in divided doses.
    • Enalapril: initially 2.5 mg once daily, increased gradually over 2–4 weeks if tolerated to 10 mg to 20 mg twice daily.
    • Fosinopril: initially 10 mg once daily, increased gradually if tolerated to 40 mg once daily.
    • Lisinopril: initially 2.5 mg once daily, increased in steps of up to 10 mg at intervals of at least 2 weeks, to a maximum of 35 mg daily.
    • Perindopril erbumine: initially 2 mg once daily for at least 2 weeks, taken in the morning, then increased if tolerated to 4 mg once daily.
    • Perindopril arginine: initially 2.5 mg once daily for 2 weeks, increased if tolerated to 5 mg once daily, taken in the morning.
    • Quinapril: initially 2.5 mg daily, increased gradually if tolerated to 10 mg to 20 mg daily in 1–2 divided doses, to a maximum of 40 mg daily.
    • Ramipril: initially 1.25 mg once daily, increased gradually at intervals of 1–2 weeks if tolerated to 10 mg daily in 1–2 divided doses, preferably in 2 divided doses.
• Before initiating an ACE inhibitor [NICE, 2025b]:
  
  • Check renal function and serum electrolytes.
    • If the person's estimated glomerular filtration rate (eGFR) is 45 ml per minute per 1.73 m² or less, consider lower starting doses and smaller dose increments.
    • If the person's eGFR is less than 30 ml per minute per 1.73 m², seek advice from a renal specialist.
    • Do not routinely initiate an ACE inhibitor in adults with chronic kidney disease (CKD) if the pre-treatment serum potassium concentration is greater than 5.0 mmol/L [NICE, 2021b].
  • Review other contraindications and cautions, and consider adverse effects and drug interactions. For more information, see the section on Angiotensin-converting enzyme inhibitors in the CKS topic on Hypertension. 
• When initiating treatment:
  • Start at the recommended initial dose and titrate to the target dose, or the highest tolerated dose.
  • Advise the person about the possibility of first-dose hypotension, particularly if they are taking a diuretic or are volume depleted. 
  • Advise the person to follow sick day guidance during episodes of diarrhoea or vomiting, including:
    • Maintaining adequate fluid intake.
    • Temporarily stopping the ACE inhibitor until they have recovered and are eating and drinking normally.
    • Seeking medical advice if symptoms persist.
• During treatment [NICE, 2025b]:
  • Check renal function and serum electrolytes 1–2 weeks after starting treatment, 1–2 weeks after each dose increase, every 3–6 months once the maximum tolerated dose has been established, and whenever renal function may be compromised.
    • Consider earlier or more frequent monitoring in people at increased risk of renal impairment or electrolyte disturbances, including those aged 60 years or over, those with CKD stage 3 or above, diabetes, or peripheral arterial disease, and those taking medicines such as a diuretic or mineralocorticoid receptor antagonist.
    • If serum creatinine increases by more than 50% or serum potassium increases to more than 5.5 mmol/L, follow local guidelines.
  • Check blood pressure, or ask the person to check their blood pressure, before and after each dose increase.
    • If the person has symptoms of postural hypotension, measure blood pressure according to recommendations in the National Institute for Health and Care Excellence (NICE) guideline on Hypertension in adults. 

Dose, titration, and monitoring of angiotensin II receptor blockers

• The angiotensin II receptor blockers (ARBs) licensed in the UK for the treatment of heart failure are candesartan, losartan, and valsartan [BNF, 2026].
  • The recommended doses are [BNF, 2026]:
    • Candesartan: initially 4 mg once daily, increased at intervals of at least 2 weeks to a target dose of 32 mg once daily, or the maximum tolerated dose.
    • Losartan: initially 12.5 mg once daily, increased at weekly intervals if tolerated to a maximum of 150 mg once daily.
    • Valsartan: initially 40 mg twice daily, increased at intervals of at least 2 weeks to a maximum of 160 mg twice daily.
• Before initiating an ARB [NICE, 2025b]:
  
  • Check renal function and serum electrolytes.
    • If the person's estimated glomerular filtration rate (eGFR) is 45 mL per minute per 1.73 m² or less, consider lower starting doses and smaller dose increments.
    • If the person's eGFR is less than 30 ml per minute per 1.73 m², seek advice from a renal specialist.
    • Do not routinely initiate an ARB in adults with chronic kidney disease (CKD) if the pre-treatment serum potassium concentration is greater than 5.0 mmol/L [NICE, 2021b].
  • Review other contraindications and cautions, and consider adverse effects and drug interactions. For more information, see the section on Angiotensin-II receptor blockers in the CKS topic on Hypertension.
• When initiating treatment:
  • Start at the recommended initial dose and titrate to the target dose, or the highest tolerated dose.
  • Advise the person about the possibility of first-dose hypotension, particularly if they are taking a diuretic or are volume depleted. 
  • Advise the person to follow sick day guidance during episodes of diarrhoea or vomiting, including:
    • Maintaining adequate fluid intake.
    • Temporarily stopping the ARB until they have recovered and are eating and drinking normally.
    • Seeking medical advice if symptoms persist.
• During treatment [NICE, 2025b]:
  • Check renal function and serum electrolytes 1–2 weeks after starting treatment, 1–2 weeks after each dose increase, every 3–6 months once the maximum tolerated dose has been established, and whenever renal function may be compromised.
    • Consider earlier or more frequent monitoring in people at increased risk of renal impairment or electrolyte disturbances, including those aged 60 years or over, those with CKD stage 3 or above, diabetes, or peripheral arterial disease, and those taking medicines such as a diuretic or mineralocorticoid receptor antagonist.
    • If serum creatinine increases by more than 50% or serum potassium increases to more than 5.5 mmol/L, follow local guidelines.
  • Check blood pressure, or ask the person to check their blood pressure, before and after each dose increase.
    • If the person has symptoms of postural hypotension, measure blood pressure according to recommendations in the National Institute for Health and Care Excellence (NICE) guideline on Hypertension in adults. 

Dose, titration, and monitoring

• The angiotensin receptor-neprilysin inhibitor (ARNI) licensed in the UK for the treatment of heart failure is sacubitril/valsartan (Entresto®).
  • The recommended doses are [BNF, 2026]:
    
    • For people not currently taking an angiotensin-converting enzyme (ACE) or angiotensin II receptor blocker (ARB), or stabilised on low doses of either: initially 50 mg twice daily for 3–4 weeks (using the 24/26 mg strength tablet) increased if tolerated to 100 mg twice daily for 3–4 weeks (using 49/51 mg strength tablet), then increased if tolerated to 200 mg twice daily (using the 97/103 mg strength tablet). 
    • For people currently stabilised on an ACE inhibitor or ARB: initially 100 mg twice daily for 2–4 weeks, then increased if tolerated to 200 mg twice daily. If systolic blood pressure is between 100–110 mmHg, consider an initial dose of 50 mg twice daily for 2–4 weeks, then increase to 100 mg twice daily for 2–4 weeks, then increase if tolerated to 200 mg twice daily. 
  • If switching from an ACE inhibitor, allow a 36-hour washout period before starting the ARNI to reduce the risk of angioedema.
• Before initiating an ARNI [NICE, 2025b; BNF, 2026]:
  • Check blood pressure.
    • Do not initiate sacubitril/valsartan (Entresto®) if systolic BP less than 100 mmHg.
  • Check renal function and serum electrolytes.
    • If the person's estimated glomerular filtration rate (eGFR) is 45 mL per minute per 1.73 m² or less, consider lower starting doses and smaller dose increments.
    • If the person's eGFR is less than 30 mL per minute per 1.73 m², seek advice from a renal specialist.
    • Do not initiate sacubitril/valsartan (Entresto®) if serum-potassium concentration is above 5.4 mmol/L.
  • Check liver function.
    • If the person has moderate hepatic impairment, or hepatic transaminases exceed twice the upper limit of normal, start with 50 mg twice daily.
  • Review other contraindications and cautions, and consider adverse effects and drug interactions.
• When initiating treatment:
  • Start at the recommended initial dose and titrate to the target dose, or the highest tolerated dose.
  • Advise the person about the risk of hypotension, particularly if they are taking a diuretic or are volume depleted.
  • Advise the person to follow sick day guidance during episodes of diarrhoea or vomiting, including:
    • Maintaining adequate fluid intake.
    • Temporarily stopping the ARNI until they have recovered and are eating and drinking normally.
    • Seeking medical advice if symptoms persist.
• During treatment [NICE, 2025b]:
  
  • Check renal function and serum electrolytes 1–2 weeks after starting treatment, 1–2 weeks after each dose increase, every 3–6 months once the maximum tolerated dose has been established, and whenever renal function may be compromised.
    • Consider earlier or more frequent monitoring in people at increased risk of renal impairment or electrolyte disturbances, including those aged 60 years or over, those with CKD stage 3 or above, diabetes, or peripheral arterial disease, and those taking medicines such as a diuretic or mineralocorticoid receptor antagonist.
    • If serum creatinine increases by more than 50% or serum potassium increases to more than 5.5 mmol/L, follow local guidelines.
  • Check blood pressure, or ask the person to check their blood pressure, before and after each dose increase.
    • If the person has symptoms of postural hypotension, measure blood pressure according to recommendations in the National Institute for Health and Care Excellence (NICE) guideline on Hypertension in adults. 

Contraindications and cautions

• Do not prescribe sacubitril/valsartan (Entresto®) to:
  • People with [EMC, 2025a; BNF, 2026]:
    • Diabetes who are taking an aliskiren-containing medicine.
    • An estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m² who are taking an aliskiren-containing medicine.
    • A history of angioedema related to previous treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB).
    • Hereditary or idiopathic angioedema.
    • Severe hepatic impairment, biliary cirrhosis, or cholestasis.
    • Systolic BP less than 100 mmHg — limited data available.
    • Serum-potassium concentration above 5.4 mmol/L — may increase risk of hyperkalaemia. 
  • Pregnant women in the second and third trimesters — ARB exposure is associated with fetal and neonatal toxicity.
• Avoid sacubitril/valsartan (Entresto®) [EMC, 2025a]:  
  • In end-stage renal disease — due to lack of clinical experience in this population.
  • During the first trimester of pregnancy — reproductive toxicity has been demonstrated in animal studies.
  • During breastfeeding — sacubitril and its active metabolite are excreted in breast milk in small amounts.
• Use sacubitril/valsartan (Entresto®) with caution in [EMC, 2025a] [BNF, 2026]:
  
  • Renal impairment — increased risk of hypotension; dose adjustment is needed. 
  • Moderate hepatic impairment, or hepatic transaminase levels greater than twice the upper limit of normal — dose adjustment is needed. 

For comprehensive information on contraindications and cautions for sacubitril/valsartan (Entresto®), see the British National Formulary (BNF) and the relevant Summary of Product Characteristics (SmPC).

Adverse effects

• Common adverse effects of sacubitril/valsartan (Entresto®) include [EMC, 2025a] [BNF, 2026]:
  • Anaemia
  • Asthenia
  • Cough
  • Diarrhoea, nausea, and gastritis
  • Dizziness, headache, syncope, and vertigo
  • Electrolyte imbalance and hypoglycaemia
  • Hypotension
  • Renal impairment
• Other reported adverse effects include [EMC, 2025a] [BNF, 2026]:
  • Angioedema
  • Skin reactions
  • Hallucinations
  • Paranoia
  • Sleep disorders

For comprehensive information on the adverse effects of sacubitril/valsartan (Entresto®), see the British National Formulary (BNF) and the Summary of Product Characteristics (SmPC).

Drug interactions

• Important drug interactions with sacubitril/valsartan (Entresto®) include [Preston, 2026]:
  • Angiotensin-converting enzyme (ACE) inhibitors — concurrent use is contraindicated because of an increased risk of angioedema. Allow a washout period of at least 36 hours when switching between an ACE inhibitor and sacubitril/valsartan.
  • Aliskiren — concurrent use is not recommended because of an increased risk of hypotension, renal impairment, and hyperkalaemia. Concurrent use is contraindicated in people with diabetes or moderate to severe renal impairment.
• For information on interactions associated with the valsartan component of sacubitril/valsartan (Entresto®), see the section on Drug interactions with angiotensin-II receptor blockers (ARBs) in the CKS topic on Hypertension.

For comprehensive information on drug interactions with sacubitril/valsartan, see the British National Formulary (BNF) and the Summary of Product Characteristics (SmPC).

Choice of beta-blocker

• The beta-blockers licensed in the UK for the treatment of heart failure are bisoprolol, carvedilol, and nebivolol.
  • The recommended doses are [BNF, 2026]:
    • Bisoprolol: initially 1.25 mg once daily in the morning for 1 week, increased if tolerated to 2.5 mg once daily for 1 week, then 3.75 mg once daily for 1 week, then 5 mg once daily for 4 weeks, then 7.5 mg once daily for 4 weeks, and then 10 mg once daily if tolerated.
    • Carvedilol: initially 3.125 mg twice daily with food, increased at intervals of at least 2 weeks if tolerated to 6.25 mg twice daily, then 12.5 mg twice daily, then 25 mg twice daily, up to the highest tolerated dose. The maximum dose is 25 mg twice daily in people with severe heart failure or body weight less than 85 kg, and 50 mg twice daily in people weighing 85 kg or more.
    • Nebivolol (adults aged 70 years and over): initially 1.25 mg once daily for 1–2 weeks, increased if tolerated to 2.5 mg once daily for 1–2 weeks, then 5 mg once daily for 1–2 weeks, and then 10 mg once daily if tolerated.
  • If a person already taking a beta-blocker for a comorbidity, such as angina or hypertension, is clinically stable and develops heart failure with reduced ejection fraction, switch them to a beta-blocker licensed for heart failure.
• Before initiating a beta-blocker:
  • Ensure the person is clinically stable, without fluid overload or symptomatic hypotension.
  • Assess heart rhythm, heart rate, and conduction abnormalities using a 12-lead ECG.
  • Do not offer a beta-blocker to people with second-degree or third-degree heart block who do not have a pacemaker or to people with bradycardia (heart rate of less than 50 beats per minute). 
  • Do not withhold treatment with a beta-blocker solely because of age or the presence of peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease, or chronic obstructive pulmonary disease.
  • Review other contraindications and cautions, and consider adverse effects and drug interactions. For more information, see the section on beta-blockers in the CKS topic on Hypertension.
• When initiating treatment:
  • Start at the recommended initial dose and titrate slowly to the target dose, or the highest tolerated dose.
  • Advise the person:
    • That symptoms may temporarily worsen during initiation or dose titration but may improve gradually over 3–6 months.
    • To seek medical advice if symptoms worsen significantly or persist, for example increasing tiredness, fatigue, weight gain, or breathlessness.
    • Not to stop the beta-blocker without consulting a healthcare professional, as abrupt withdrawal can cause rebound worsening of myocardial ischaemia.
• After each dose increase, monitor heart rate, blood pressure, and clinical status. 
  
  • If bradycardia develops:
    • Review the need for other medicines that slow heart rate, such as digoxin, amiodarone, diltiazem, or verapamil.
    • Consider reducing the beta-blocker dose.
    • In people with symptoms, consider repeating a 12-lead ECG.
    • Seek specialist advice if there is severe clinical deterioration or concern about heart block.
  • If symptomatic hypotension develops:
    • Review other medicines that may contribute to hypotension, such as nitrates, calcium-channel blockers, or other vasodilators.
    • Consider reducing the diuretic dose if there are no signs of fluid overload.
    • Seek specialist advice if symptoms persist.
  • If heart failure symptoms worsen during titration:
    • Assess fluid status and review treatment.
    • Consider increasing the diuretic dose if there is evidence of fluid overload.
    • Consider reducing the beta-blocker dose if symptoms remain problematic.
    • Seek specialist advice if symptoms are severe or do not improve.

Dose, titration, and monitoring

• The National Institute for Health and Care Excellence (NICE) recommends diuretics for the relief of congestive symptoms and fluid retention in people with heart failure [NICE, 2025b].
  • Options include:
    • Furosemide (most commonly used): 20 mg to 40 mg daily.
    • Bumetanide: 0.5 mg to 1 mg daily.
    • Torasemide: 5 mg to 10 mg daily.
  • If higher doses are required, check adherence to treatment, consider alternative causes, and seek specialist advice or consider admission, depending on clinical judgement.
  • Loop diuretics are not indicated in people who have never had symptoms or signs of congestion.
• Before initiating a diuretic:
  • Check serum electrolytes, serum creatinine, and blood pressure.
  • Check liver function if hepatic impairment is known or suspected.
  • Review other contraindications and cautions, and consider adverse effects and drug interactions.
  • Advise the person and their carer on how to adjust the dose according to changes in weight to avoid both fluid overload and dehydration.
    • Symptoms of fluid overload may include increasing breathlessness, oedema, and rapid weight gain.
    • Symptoms of dehydration include thirst, dizziness, and fatigue.
• During treatment:
  • Check renal function and serum electrolytes 1–2 weeks after starting treatment, 1–2 weeks after each dose increase, every 3–6 months once the maximum tolerated dose has been established, and whenever renal function may be compromised.
    • Consider earlier or more frequent monitoring in people at increased risk of renal impairment or electrolyte disturbances, including those aged 60 years or over, those with CKD stage 3 or above, diabetes, or peripheral arterial disease, and those taking an angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), or mineralocorticoid receptor antagonist.
  • Check blood pressure, or ask the person to check their blood pressure, before and after each dose increase.
    • If the person has symptoms of postural hypotension, measure blood pressure according to recommendations in the NICE guideline on Hypertension in adults. 
  • Review the loop diuretic dose and adjust as necessary once dry body weight has been achieved and other heart failure treatment has been introduced, to reduce the risk of dehydration, acute kidney injury, and electrolyte disturbances.
• If an electrolyte disturbance develops:
  • Correct the abnormality as appropriate.
  • Consider whether the person is at high risk of cardiac arrhythmias with even mild hypokalaemia, including older people, those taking digoxin or medicines that prolong the QT interval (such as amiodarone), and those with paroxysmal arrhythmias, unstable angina, or chronic liver disease.
  • Seek specialist advice if the electrolyte disturbance is severe or there is uncertainty about management.

[EMC, 2025b; NICE, 2025b; BNF, 2026] 

Contraindications and cautions

• Do not prescribe furosemide to people with [EMC, 2025b; BNF, 2026]:
  
  • Anuria.
  • Severe hypovolaemia or dehydration.
  • Severe hyponatraemia or hypokalaemia.
  • Renal failure due to nephrotoxic or hepatotoxic drugs.
  • Comatose and pre-comatose states associated with hepatic cirrhosis or encephalopathy.
• Avoid furosemide [EMC, 2025b]:
  
  • During pregnancy — furosemide crosses the placenta and should only be used during pregnancy if there are compelling medical reasons. If treatment is required, monitor fetal growth. 
  • During breastfeeding — furosemide passes into breast milk and may inhibit lactation.
• Use furosemide with caution in [EMC, 2025b; BNF, 2026]:
  • Older people — increased susceptibility to adverse effects; monitor serum sodium and potassium levels.
  • People with:
    
    • Electrolyte disturbances, particularly hypokalaemia and hyponatraemia.
    • Difficulty with micturition, including prostatic hypertrophy — increased risk of urinary retention; closely monitor people with partial occlusion of the urinary tract.
    • Diabetes — latent diabetes may become overt and insulin requirements may increase in people with established diabetes.
    • Gout — increased risk of hyperuricaemia.
    • Impaired hepatic function (during long-term therapy, especially at high doses).
    • Impaired renal function — closely monitor renal function and serum electrolytes.
    • Hypoproteinaemia (for example nephrotic syndrome) — the effect of furosemide may be reduced and the risk of ototoxicity increased; cautious dose titration is required.
    • Hepatorenal syndrome.

For comprehensive information on contraindications and cautions for furosemide and other loop diuretics, see the British National Formulary (BNF) and the relevant Summary of Product Characteristics (SmPC).

Adverse effects

• Common adverse effects of furosemide include [EMC, 2025b; BNF, 2026]:
  • Acute kidney injury.
  • Dehydration and hypovolaemia.
  • Dizziness.
  • Electrolyte disturbances, particularly hypokalaemia, hyponatraemia, hypomagnesaemia, hypocalcaemia, and metabolic alkalosis.
  • Gastrointestinal disturbances.
  • Hyperuricaemia (which may precipitate gout).
  • Hyperglycaemia or impaired glucose tolerance.
  • Hypotension.
  • Increased serum creatinine and urea.
  • Muscle cramps.
• Rare or serious adverse effects include [EMC, 2025b; BNF, 2026]:
  • Acute pancreatitis.
  • Blood dyscrasias.
  • Interstitial nephritis.
  • Severe hypersensitivity and skin reactions.

For comprehensive information on adverse effects of furosemide and other loop diuretics, see the British National Formulary (BNF) and the relevant Summary of Product Characteristics (SmPC).

Drug interactions

• Important drug interactions with furosemide include [EMC, 2025b; BNF, 2026]:
  • Medicines that affect the renin–angiotensin–aldosterone system, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) — increased risk of hypotension, renal impairment, and electrolyte disturbances.
    • Monitor renal function, serum electrolytes, and blood pressure.
  • Other antihypertensives and nitrates — increased risk of hypotension.
    • Monitor blood pressure.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) — may reduce the diuretic effect, worsen renal function, and promote sodium and fluid retention, potentially exacerbating heart failure.
    • Avoid concurrent use where possible.
  • Digoxin — furosemide-induced hypokalaemia may increase the risk of digoxin toxicity.
    • Monitor serum potassium.
  • Other diuretics — increased risk of excessive diuresis, hypotension, renal impairment, and electrolyte disturbances.
    • Monitor closely.
  • Lithium — increased risk of lithium toxicity.
    • Avoid concurrent use unless serum lithium concentrations can be monitored closely.
  • Medicines that may increase the risk of arrhythmias, such as amiodarone, disopyramide, flecainide, quinidine, and sotalol — furosemide-induced hypokalaemia may increase the risk of arrhythmias.
    • Monitor serum potassium and correct hypokalaemia as appropriate.
  • Medicines that may increase the risk of hypokalaemia, such as corticosteroids and laxatives — may further increase potassium loss when used with furosemide.
    • Monitor serum potassium and correct hypokalaemia as appropriate.

For comprehensive information on drug interactions with furosemide and other loop diuretics, see the British National Formulary (BNF) and the relevant Summary of Product Characteristics (SmPC).

Dose, titration, and monitoring

• The sodium-glucose cotransporter-2 (SGLT2) inhibitors used for the treatment of heart failure are dapagliflozin and empagliflozin.
  • The recommended doses are [BNF, 2026]:
    • Dapagliflozin: 10 mg once daily.
    • Empagliflozin: 10 mg once daily.
• Before initiating treatment:
  • Check renal function.
    • Avoid initiating dapagliflozin if the estimated glomerular filtration rate (eGFR) is less than 15 mL/min/1.73 m².
    • Avoid initiating empagliflozin if the eGFR is less than 20 mL/min/1.73 m².
  • Check hepatic function:
    • In severe impairment, start dapagliflozin at 5 mg once daily and increase to 10 mg once daily if tolerated.
    • Avoid empagliflozin in severe impairment.
  • Assess volume status, particularly in people taking a diuretic or at risk of volume depletion, such as older people (aged 65 years or older) [BNF, 2026; EMC, 2026a].
    • Correct hypovolaemia before starting treatment.
  • Review other contraindications and cautions, and consider adverse effects and drug interactions. For more information, see the section on SGLT2 inhibitors in the CKS topic on Diabetes - type 2.
• During treatment:
  • Advise the person to follow sick day guidance during episodes of diarrhoea or vomiting, including:
    • Maintaining adequate fluid intake.
    • Temporarily stopping the SGLT2 inhibitor until they have recovered and are eating and drinking normally.
    • Seeking medical advice if symptoms persist.
  • Advise the person to seek urgent medical advice if they develop:
    • Symptoms suggestive of diabetic ketoacidosis, such as nausea, vomiting, abdominal pain, excessive thirst, difficulty breathing, confusion, or unusual fatigue. 
    • Symptoms suggestive of Fournier’s gangrene, such as pain, tenderness, redness, or swelling in the genital or perineal area, particularly with fever or malaise.
       

Dose, titration, and monitoring

• The mineralocorticoid receptor antagonists (MRAs) licensed in the UK for the treatment of heart failure are spironolactone and eplerenone [BNF, 2026].
  • The recommended doses are [BNF, 2026]:
    • Spironolactone: initially 25 mg once daily, then adjusted according to response to 50 mg once daily.
    • Eplerenone: initially 25 mg once daily, then increased to 50 mg once daily within 4 weeks of starting treatment.
• Before initiating an MRA [NICE, 2025b]:
  • Check renal function and serum electrolytes.
    • If the person's estimated glomerular filtration rate (eGFR) is 45 mL/min/1.73 m² or less, consider a lower starting dose and smaller dose increments.
    • If the person's eGFR is less than 30 mL/min/1.73 m², seek advice from a renal specialist.
    • Do not initiate eplerenone if serum potassium is greater than 5.0 mmol/L [EMC, 2026b].
    • Do not initiate spironolactone in people with hyperkalaemia [EMC, 2026c]. 
  • Check hepatic function.
    • Do not initiate eplerenone in severe hepatic insufficiency (Child-Pugh class C).
  • Review other contraindications and cautions, and consider adverse effects and drug interactions. 
• When initiating treatment:
  • Start at the recommended initial dose and titrate to the target dose, or the highest tolerated dose.
  • Advise the person to follow sick day guidance during episodes of diarrhoea or vomiting, including:
    • Maintaining adequate fluid intake.
    • Temporarily stopping the MRA until they have recovered and are eating and drinking normally.
    • Seeking medical advice if symptoms persist.
• During treatment [NICE, 2025b]:
  • Check renal function and serum electrolytes 1–2 weeks after starting treatment, 1–2 weeks after each dose increase, every 3–6 months once the maximum tolerated dose has been established, and whenever renal function may be compromised.
    • Consider earlier or more frequent monitoring in people at increased risk of renal impairment or electrolyte disturbances, including those aged 60 years or over, those with chronic kidney disease, diabetes, or peripheral arterial disease, and those taking medicines such as a diuretic or angiotensin-converting enzyme (ACE) inhibitor.
    • If serum creatinine increases by more than 50% or serum potassium increases to more than 5.5 mmol/L, follow local guidelines.
  • Check blood pressure, or ask the person to check their blood pressure, before and after each dose increase.
    • If the person has symptoms of postural hypotension, measure blood pressure according to recommendations in the National Institute for Health and Care Excellence (NICE) guideline on Hypertension in adults. 

Contraindications and cautions

• Do not prescribe eplerenone to people with [EMC, 2026b]:
  • Serum potassium greater than 5.0 mmol/L at initiation.
  • Severe renal impairment — estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m².
  • Severe hepatic impairment — Child-Pugh class C.
• Do not prescribe spironolactone to people with [EMC, 2026c]:
  • Hyperkalaemia.
  • Acute renal insufficiency, significant renal impairment, or anuria.
  • Addison's disease.
• Avoid spironolactone [EMC, 2026c]:
  • During pregnancy — limited human data are available, and animal studies have shown reproductive toxicity related to its anti-androgenic effects. Use only if the potential benefit justifies the potential risk.
  • During breastfeeding — canrenone, an active metabolite, is excreted in human milk. If treatment is required, consider whether to discontinue breastfeeding or spironolactone, taking into account the benefits of breastfeeding and treatment.
• Use MRAs with caution in [EMC, 2026b; EMC, 2026c]: 
  • Older people.
  • People with:
    
    • Diabetes, particularly with microalbuminuria — increased risk of hyperkalaemia.
    • Mild to moderate renal impairment.
    • Mild to moderate hepatic impairment (eplerenone).
  • Pregnant women (eplerenone) — there are no adequate data from use in pregnant women. Animal studies have not shown direct or indirect reproductive toxicity; prescribe with caution.
  • Breastfeeding women (eplerenone) — it is unknown whether eplerenone is excreted in human milk. Consider whether to discontinue breastfeeding or eplerenone, taking into account the benefit of breastfeeding for the child and treatment for the woman.   

For comprehensive information on contraindications and cautions for MRAs, see the British National Formulary (BNF) and the relevant Summary of Product Characteristics (SmPC).

Adverse effects

• Adverse effects of mineralocorticoid receptor antagonists (MRAs) include [BNF, 2026] [EMC, 2026b; EMC, 2026c]: 
  • Acute kidney injury and worsening renal function.
  • Blood disorders (including agranulocytosis, leucopenia, and thrombocytopenia).
  • Confusion, dizziness, and syncope.
  • Cough.
  • Electrolyte disturbances (particularly hyperkalaemia).
  • Gastrointestinal disturbances (including nausea, vomiting, constipation, and diarrhoea).
  • Gynaecomastia and other endocrine effects (particularly with spironolactone).
  • Hepatic dysfunction.
  • Hypotension.
  • Insomnia.
  • Reduced libido and other sexual dysfunction (particularly with spironolactone).
  • Malaise and asthenia.
  • Muscle cramps or spasms.
  • Skin reactions, including severe cutaneous adverse reactions (SCARs).

For comprehensive information on other possible adverse effects of MRAs, see the British National Formulary (BNF) and the relevant Summary of Product Characteristics (SmPC).

Drug interactions

• Important drug interactions with mineralocorticoid receptor antagonists (MRAs) include [BNF, 2026] [EMC, 2026b; EMC, 2026c]: 
  • Strong CYP3A4 inhibitors (for example, ketoconazole, itraconazole, voriconazole, and clarithromycin) — markedly increase eplerenone exposure.
    • Concurrent use with eplerenone is contraindicated.
  • Moderate CYP3A4 inhibitors (for example, erythromycin) — increase eplerenone exposure.
    • Dose reduction may be required in accordance with the product licence.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) — may reduce the antihypertensive and diuretic effects of MRAs and increase the risk of renal impairment and hyperkalaemia.
    • Avoid where possible or monitor renal function and potassium closely.
  • Lithium — may increase lithium concentrations and toxicity. 
    • Avoid concurrent use where possible, or monitor lithium concentrations closely.
  • Medicines that increase serum potassium concentration (for example angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), angiotensin receptor–neprilysin inhibitors (ARNIs), potassium supplements, potassium-containing salt substitutes, trimethoprim, and other potassium-sparing diuretics)  — increased risk of hyperkalaemia.
    • Monitor serum potassium and renal function closely.

For comprehensive information on drug interactions with MRAs, see the British National Formulary (BNF) and the relevant Summary of Product Characteristics (SmPC).