Key Points
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All patients diagnosed with heart failure due to left ventricular systolic dysfunction should be considered for an ACEI
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This advice applies to monitoring of pharmacotherapy in clinically stable patients; it does NOT apply to patients with intercurrent acute illness
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Please ensure patient has a genuine AKI (rapidly deteriorating renal function) before prognostic medication is discontinued
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If prognostic medication is stopped due to AKI/acutely unwell patient, please consider restarting if renal function recovers
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Abbreviations
Guideline rationale
Evidence from clinical trials suggest that patients with, or at risk of developing heart failure show an improvement in symptoms and a reduction in morbidity and mortality when treated with an ACEI. Therefore, all patients diagnosed with heart failure due to left ventricular systolic dysfunction should be considered for an ACEI.
This advice applies to monitoring of pharmacotherapy in clinically stable patients; it does NOT apply to patients with intercurrent acute illness.
Contra-indications
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Bilateral renal artery stenosis, refer patients for advice
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Aortic or mitral valve stenosis or obstructive cardiomyopathy, refer patients for advice
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Known hypersensitivity to ACEI or excipients or to any other ACEI
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History of angioedema of any cause
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Pregnancy
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Baseline potassium > 5.5 mmol/L
Cautions
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Hypotension (systolic blood pressure (BP)< 90mmHg)
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Patients with a documented intolerance of ACEI due to symptomatic hypotension - consider re-challenging with a longer acting ACEI (such as ramipril). Care if asymptomatic hypotension (systolic BP< 90mmHg)
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Patients on high dose diuretics (i.e., furosemide > 80mg daily) – increased risk of hypotension and renal dysfunction
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Breast feeding
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Moderate to severe renal impairment: creatinine >150μmol/L or eGFR< 50ml/min
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Baseline potassium > 5 to 5.5mmol/l
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Patients on haemodialysis
Consider referral prior to initiation
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Hypertrophic cardiomyopathy
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Hyponatraemia (<130mmol/L)
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Symptomatic or severe asymptomatic hypotension (systolic BP<90mmHg
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Significant renal dysfunction/renovascular disease, e.g., creatinine > 150 μmol/l or eGFR < 50ml/min or hyperkalaemia (K>5.0mmol/L)
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Renovascular disease (diagnosed as well as undiagnosed and clinically silent disease), e.g., PVD or severe generalised atherosclerosis
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Patients undergoing dialysis/extracorporeal treatments or having desensitisation with wasp or bee venom
Initiation and monitoring
Check pre-treatment blood chemistry (serum creatinine, urea, potassium, sodium and eGFR) and blood pressure.
Use the immediate pre-treatment serum creatinine concentration as the baseline.
Stop potassium supplements/potassium sparing diuretics (except spironolactone or eplerenone) and review need for concomitant nephrotoxic drugs, e.g., NSAIDs.
Review dose of diuretic therapy.
Start with the lowest recommended dose of ACEI and titrate as suggested below. Aim for the target dose, failing that, the maximum tolerated dose. Some ACEI is better than no ACEI.
ACEI are disease modifying drugs in patients with HFrEF which improve patient outcomes. The risk of stopping or reducing dose is, in general, likely to be of greater detriment to a patient’s prognosis than a modest increase in serum creatinine, or mild hyperkalaemia.
Amongst patients with heart failure and normal ejection fraction (HFpEF or diastolic heart failure), there is no convincing evidence that ACEI alter prognosis. If renal function deteriorates significantly with their use, consider stopping them altogether and using an alternative agent.
For HFmrEF, ACE inhibitors may be considered as additional therapy to reduce mortality and hospitalisation
Dose Titration
BP and blood chemistry (e.g., serum creatinine, urea, potassium, sodium and eGFR) should be checked within one to two weeks of initiation or change of dose.
When maximum tolerated dose or target dose achieved; measure serum creatinine, urea, potassium and eGFR monthly for 3 months, then a minimum of every 6 months and at any time the person becomes acutely unwell.
Reduce dose/stop according to “worsening renal function” and “symptomatic hypotension” in “problem solving” below.
ACEI dose can be doubled at no less than 2 weekly intervals if appropriate. Smaller increments may be more clinically suitable for certain patients.
RAMIPRIL is the first choice ACE inhibitor (Initial dose 1.25mg, target dose 10mg).
Problem Solving
Angioedema
Rare but life threatening. Stop therapy and seek immediate advice from accident and emergency.
Asymptomatic low blood pressure
Does not usually warrant a change in therapy.
Symptomatic low blood pressure
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Consider dehydration and address as appropriate.
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Review diuretic dose with a view to decreasing dose if patient free of symptoms suggestive of fluid retention.
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If dizziness and light-headedness and/or confusion occur, consider stopping nitrates, calcium channel blockers and other vasodilators first, and then consider reducing dose of beta-blocker. Monitor closely and allow longer intervals between dose titrations. Consider reduction of ACEI dose to the previous tolerated dose.
Seek specialist advice if measures do not resolve symptomatic hypotension.
Persistent dry cough
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Review aetiology of cough, e.g., due to smoking, worsening heart failure/pulmonary oedema, respiratory disease or ACEI therapy.
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Review cough tolerability versus benefits of an ACEI. Some patients may tolerate restarting the ACEI after a drug free period.
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Rarely requires stopping treatment. If significantly affecting the patient’s quality of life, please consider ARNI or ARB licensed for heart failure.
Worsening renal function
ACEI are disease modifying drugs in patients with HFrEF so they improve patient outcomes. The risk of stopping or reducing dose is, in general, likely to be of greater detriment to a patient’s prognosis than a modest increase in serum creatinine, or mild hyperkalaemia.
These guidelines are generally for management of CKD.
An increase in urea, creatinine and K+ is to be expected after initiation/titration of ACEI. If the increase is small and asymptomatic, no action is necessary. Please see the table below for recommended actions.
Please ensure patient has a genuine AKI (rapidly deteriorating renal function) before prognostic medication is discontinued.
If prognostic medication is stopped due to AKI/acutely unwell patient, please consider restarting if renal function recovers. Please liaise with the heart failure team for further advice.
Potassium
Mild hyperkalaemia (5.5 – 5.9mol/L)
Management depends on clinical context.
If the patient is acutely unwell, or has AKI, stop the ACEI and consider referral to hospital.
If the patient is clinically stable (i.e. the test was done as a routine check, and there is no AKI warning stage test result), undertake medication review.
If hyperkalaemia is unexpected, consider arranging a repeat test within 3 days, taking steps to minimise any of the factors that can cause artifactual hyperkalaemia.
(a) Look for and remove other contributors to hyperkalaemia, including trimethoprim/co-trimoxazole, potassium supplements, potassium-sparing diuretics, salt substitutes e.g. ‘LoSalt’, NSAIDs, non-selective beta-blockers, digoxin toxicity.
(b) Review the patient clinically: reduce/stop diuretics if evidence of over-diuresis.
(c) Consider halving dose of ACEI, and review indications (NB patients should not be treated with combinations of ACEI and ARB).
Provide patients with a diet advice sheet on reduction of potassium intake.
If problems with hyperkalaemia persist, refer for dietetic advice.
Consider seeking advice from local heart failure specialist team if the indication for treatment was HFrEF.
Moderate hyperkalaemia (6.0-6.4mmol/L)
Management depends on clinical context.
Stop ACEI.
If the patient is acutely unwell, or has AKI refer to hospital for immediate assessment.
If the patient is clinically stable (i.e., the test was done as a routine check rather than for acute illness, and there is no AKI warning stage test result), undertake medication review within 1 working day of the result.
Re-start at lower dose once serum K≤5.5 mmol/L and continue to monitor.
If patient on combination of ACEI and/or ARB, or (ARNI) with MRA, only restart one of these drugs at a time.
If hyperkalaemia is unexpected, consider arranging a repeat test the following day taking steps to minimise any of the factors that can cause artefactual hyperkalaemia.
Look for and remove other contributors to hyperkalaemia as indicated in ‘mild hyperkalaemia’.
Review the patient clinically reduce/stop diuretics if evidence of over diuresis.
Severe hyperkalaemia (≥ 6.5 mmol/L)
Refer to hospital (via A&E) for immediate assessment and treatment.
Creatinine
Creatinine ↑ > 15% but <30% from initial baseline
Continue, but repeat U&Es in a further 1 to 2 weeks.
(a) Arrange clinical review including assessment of fluid status and blood pressure.
(b) Try to continue ACEI treatment.
(c) Reduce or stop other BP lowering drugs (e.g., calcium channel blockers, alpha blockers) if SBP <120 mmHg.
(d) Reduce concurrent diuretics if there is clinical evidence of hypovolaemia/over diuresis.
If the patient is acutely unwell, or has AKI consider stopping the ACEI.
Creatinine increases at any point by ≥ 30% from initial baseline
Arrange clinical review including assessment of fluid status and blood pressure. Consider:
(a) Try to continue ACEI treatment;
(b) Reduce or stop other BP lowering drugs (eg. calcium channel blockers, alpha blockers) if SBP <120 mmHg;
(c) Reduce concurrent diuretics if there is clinical evidence of hypovolaemia/overdiuresis;
(d) Re-check renal function within 5-7 days.
If the patient is acutely unwell, or has AKI, consider stopping the ACEI and referral to hospital.
If serum creatinine remains >30% from initial baseline with above measures
(a) Stop the ACEI or reduce the dose to a previously tolerated dose and re-check renal function in 5-7 days; add an alternative antihypertensive medication if required.
(b) Obtain advice from local heart failure specialist team if the indication for treatment was HFrEF: continuing an ACEI in HFrEF may be beneficial even if serum creatinine rises by >30%.
(c) Consider obtaining advice from nephrology, even if serum creatinine returns to baseline.
If the patient is acutely unwell, or has AKI, stop the ACEI and consider referral to hospital.
References
Think Kidneys, the Renal Association and the British Society for Heart Failure (2017) Changes in kidney function and serum potassium during ACEI/ARB/ diuretic treatment in primary care: A position statement from Think Kidneys, the Renal Association and the British Society for Heart Failure. Available at: https://www.thinkkidneys.nhs.uk/aki/wp-content/uploads/sites/2/2017/10/Changes-in-Kidney-Function-FINAL.pdf (Accessed 07.03.22)
National Institute for Health and Care Excellence (2018). Chronic Heart Failure in Adults: Diagnosis and Management. NICE Clinical Guideline CG106. Available at: https://www.nice.org.uk/guidance/ng106 (Accessed 07.03.22)
Theresa A McDonagh et al, 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC, European Heart Journal, Volume 42, Issue 36, 21 September 2021, Pages 3599–3726, https://doi.org/10.1093/eurheartj/ehab368 (Accessed 07.03.22).
Correction published 21 December 2021, https://doi.org/10.1093/eurheartj/ehab670
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