Prescribing recommendations for heart failure: guideline in a nutshell

The recent update to NICE’s guideline on the management of heart failure focuses predominantly on prescribing, and recognises the increasing body of evidence for the benefits of SGLT2 inhibitors in reducing mortality and hospitalisations for heart failure

HEART FAILURE WITH REDUCED EJECTION FRACTION (HFrEF)

NICE now recommends adding an SGLT2 inhibitor to existing treatment with an ACE inhibitor or angiotensin receptor blocker (ARB), beta-blocker for patients with heart failure with reduced ejection fraction (HFrEF). Adding an SGLT2 inhibitor improves outcomes, without causing important increases in adverse events.

Reductions in mortality and hospitalisations were also seen when a mineralocorticoid receptor antagonist (MRA) was added to existing treatment with an ACE inhibitor or ARB and beta-blocker, and although this combination has been shown to increase the risk of hyperkalaemia, NICE suggests that an MRA should remain part of the regimen for patients with HFrEF.

For people on the maximum tolerated dose of each of these four medicines who continue to experience symptoms, NICE suggests switching the ACE inhibitor to an angiotensin receptor-neprilysin inhibitor (ARNI).

Where people with HFrEF have symptoms of intolerance to ACE inhibitors, other than angioedema), offer an ARNI, beta-blocker, MRA and SGLT2 inhibitor. If the person is intolerant of an ARNI, the alternative strategy is to offer a beta-blocker, MRA and SGLT2 inhibitor and to consider adding an ARB.

Economic modelling using both clinical trial and real-world data indicated that starting an MRA and SGLT2 inhibitor early, alongside an ACE inhibitor and beta-blocker, would be cost-effective. As individual patients may need different sequences of medications, the committee decided not to provide step-by-step recommendations for introducing each drug. Instead, they outlined various treatment combinations tailored to different situations.

The guideline development committee (GDC) noted that evidence showed a reduction in both all-cause and cardiovascular mortality for patients treated with an ARNI, beta-blocker, and MRA compared to those taking an ACE inhibitor, beta-blocker, and MRA. However, people on an ARNI experienced more falls, while hyperkalaemia was reported more often with ACE inhibitors. The committee concluded that an ARNI can substitute for an ACE inhibitor in individuals who continue to have symptoms despite being on an ACE inhibitor, beta-blocker, MRA, and SGLT2 inhibitor combination. If this regimen is already improving symptoms, replacing the ACE inhibitor with an ARNI isn’t recommended due to lower cost-effectiveness. Clinicians are also reminded to allow at least 36 hours between the last ACE inhibitor dose and the first ARNI dose.

These recommendations are not expected to make a significant difference to current practice, as many patients with HFrEF are already being prescribed an SGLT2 inhibit or ARNI. However, the recommendations may accelerate this trend. The increase in prescribing costs is likely to be offset by a reduction in the number of hospital admissions.

HEART FAILURE WITH MILDLY REDUCED (HFmrEF)

NICE’s recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) echo those for people with HFrEF. Treatment should include an ACE inhibitor, a beta-blocker, an MRA and an SGLT2 inhibitor. Where an ACE inhibitor is not tolerated, consider an ARB.

The two recommended SGLT2 inhibitors are empagliflozin and dapagliflozin.

Although this is a new recommendation for NICE, most people in this population will already be receiving a combination of these medicines. The main impact of formalising their use is that consultations may need to be extended to establish the correct combination and dose of each drug.

HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFpEF)

The two medications recommended for the treatment of heart failure with preserved ejection fraction (HFpEF) are an MRA and an SGLT2 inhibitor – either empagliflozin or dapagliflozin.

There is evidence that treatment with an MRA reduces hospitalisation for heart failure and may also improve all-cause and cardiovascular mortality in people with HFpEF. MRA treatment is associated with an increased risk of hyperkalaemia, but although this requires careful monitoring and management, the GDC agreed this should not prevent them from recommending MRAs for this population group.

This recommendation is considered a significant change to current practice, and its impact will include extra clinician time to establish the correct dose of MRA, and treatment of hyperkalaemia.

IRON DEFICIENCY

Iron deficiency is common in heart failure, occurring in about 50% of patients. NICE has therefore added a recommendation to assess iron status and check for anaemia in people with heart failure with all of the following blood tests:

• Transferrin saturation (TSAT)
• Serum ferritin
• Haemoglobin

Patients with haemoglobin of less than 150g/L and a TSAT of less than 20% or serum ferritin of less than 100 µg/L should be referred for intravenous iron therapy. However, if iron deficiency anaemia is identified, it should not be assumed to be related to heart failure and clinicians should consider investigating for alternative causes – while aiming for a balance against over-investigation.

The recommended preparations are iron sucrose, ferric carboxymaltose or ferric derisomaltose.

Evidence shows IV iron improves exercise tolerance and quality of life in the first year for people with HFrEF and iron deficiency. Some trials also showed reduced hospitalisation for heart failure. One study showed a significant risk of hypophosphatemia with ferric carboxymaltose. As hypophosphatemia can be monitored and treated, the committee agreed that the risk of this did not outweigh the expected benefits of IV iron.

The use of IV iron therapy is already fairly common practice, but it is not universal. Wider adoption might help to reduce hospitalisations. An addition to this guideline update is the recommendation to include an assessment of iron status and haemoglobin at each clinical review.

INITIATING AND MONITORING TREATMENT

As NICE no longer recommends a particular sequence for the introduction of drugs for the treatment of heart failure, the choice of which specific medicines and combinations to use will depend on the individual’s medical history, and findings from their clinical assessment, frailty status, prognosis and the patient’s preferences.

Clinicians should also consider the order and timing for initiating each medicine, the initial dose of each medicine, and any subsequent dose increases, as well as how to optimise the dose of each drug.

NICE recommends that primary care prescribers should take advice from a heart failure specialist before initiating an ARNI.

Before prescribing any of the treatment classes for heart failure, clinicians should measure the patient’s renal function and electrolyte levels. These should also be reviewed 1 – 2 weeks after starting treatment or each dose increase, and every 3 – 6 months once the maximum tolerated dose has been established.

DO NOT DO

Do not withhold treatment with a beta-blocker because of a patient’s age, or the presence of peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease or chronic obstructive pulmonary disease (COPD). Check heart rhythm, heart rates and for conduction abnormalities using a 12-lead ECG before deciding to offer a beta-blocker.

Do not prescribe a beta-blocker to people with second- or third-degree heart block who do not have a pacemaker, or to people with a heart rate of less that 50 bpm (bradycardia).

Do not routinely advise people with heart failure to restrict their sodium or fluid intake. However, consider fluid restriction for people with dilutional hyponatraemia and reducing intake for people with high levels of salt or fluid consumption. Advise people to avoid salt substitutes than contain potassium.

CLINICAL REVIEW

Patients with heart failure should be monitored regularly – at least twice a year, and more frequently if they have comorbidities or are on multiple medications. If their clinical condition, or their medication, has changed monitor at least every 2 weeks.

The review should include:

• Clinical assessment of functional capacity
• Fluid status
• Cardiac rhythm (pulse check as minimum)
• Cognitive and nutritional status
• Review of medication, including the need for changes and any side effects
• Renal function assessment
• Iron status and haemoglobin measurement

WHEN TO REFER

Seek specialist advice for patients with persistent symptoms. Consider:

• Ivabradine if sinus rhythm and heart rate of 75 bpm or more and ejection fraction is 35% or less
• Digoxin for worsening or severe heart failure despite optimised treatment combinations
• Cardiac resynchronisation therapy if QRS interval of 120 or more and ejection fraction is 35% or less
• Hydralazine and nitrate instead of an ACE inhibitor for patients with symptoms of intolerance to ACE inhibitors, ARNIs and ARBs

SOURCE

NICE NG106. Chronic heart failure in adults: diagnosis and management; last updated September 2025. https://www.nice.org.uk/guidance/ng106