Rationale and impact
These sections briefly explain why the committee made the recommendations and how they might affect practice.
Treatment combinations for heart failure with reduced ejection fraction
Recommendations 1.4.1 to 1.4.4
Why the committee made the recommendations
Evidence showed adding a sodium-glucose cotransporter-2 (SGLT2) inhibitor to existing treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), beta-blocker and mineralocorticoid receptor antagonist (MRA) reduced mortality and hospitalisation for heart failure without important increases in adverse events. The committee agreed that treatment combinations for people with heart failure with reduced ejection fraction should now include an SGLT2 inhibitor.
Similar benefits were seen when adding an MRA to existing treatment with an ACE inhibitor or ARB and beta-blocker although there was an increased risk of hyperkalaemia. The committee agreed an MRA should remain part of the treatment combination for people with heart failure with reduced ejection fraction.
Economic modelling based on the clinical trials and real-world data suggested that early use of an MRA and SGLT2 inhibitor in combination with ACE inhibitor and beta-blocker would be cost-effective. For this reason and because the correct sequencing of medicines will vary from 1 person to another, the committee agreed to move away from a set of recommendations that include a sequence for introducing each medicine and instead listed treatment combinations for different scenarios.
Evidence comparing treatment with an ACE inhibitor, beta-blocker and MRA against treatment with an angiotensin receptor-neprilysin inhibitor (ARNI), beta-blocker and MRA showed reduced all-cause and cardiovascular mortality for the group of people taking the treatment combination with an ARNI. More falls were seen in those taking an ARNI, while hyperkalaemia was more common among those taking an ACE inhibitor. The committee agreed that an ARNI can replace an ACE inhibitor in people who remain symptomatic when receiving the combination of ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor. However, where this combination is providing symptomatic improvement, switching to an ARNI is not advised because it is not as cost effective as an ACE inhibitor. The committee was aware that there should be a period of at least 36 hours between taking the last dose of an ACE inhibitor and the first dose of an ARNI.
Economic modelling showed that ARNIs were cost effective compared to ARBs. The committee agreed that an ARNI should be offered instead of an ACE inhibitor to people who have symptoms of intolerance to ACE inhibitors (other than angioedema). The previous first choice in this situation was an ARB. The committee agreed that an ARB can still be used for people with angioedema after taking an ACE inhibitor, or who have symptoms of intolerance to ARNIs.
How the recommendations might affect practice
Growing numbers of people with heart failure with reduced ejection fraction are being prescribed an SGLT2 inhibitor or ARNI and these recommendations are likely to accelerate this trend. There is likely to be a reduction in hospitalisation for heart failure as a result of this change in prescribing.
Intravenous iron therapy for heart failure with reduced ejection fraction
Recommendations 1.4.5 to 1.4.7
Why the committee made the recommendations
Evidence showed intravenous (IV) iron (iron sucrose, ferric carboxymaltose or ferric derisomaltose) improved exercise tolerance and quality of life in the first year for people with heart failure with reduced ejection fraction 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.
There was evidence that IV iron therapy is cost-effective in people with heart failure with reduced ejection fraction and iron deficiency and so the committee focused on this population. They agreed to define iron deficiency according to the definition used in the trials.
To support the recommendation on when to consider IV iron, the committee made a recommendation to assess iron status with blood tests for transferrin saturation (TSAT) and serum ferritin, as well as measuring haemoglobin to check for anaemia.
The committee highlighted the importance of considering alternative causes of iron deficiency anaemia when it is identified, but also the need to get the correct balance against over-investigating.
As only 1 small trial was available for the mildly reduced or preserved ejection fraction population, the committee made a recommendation for research on use of IV iron therapy in adults with iron deficiency and heart failure with mildly reduced or preserved ejection fraction.
How the recommendations might affect practice
The use of IV iron therapy to treat iron deficiency in people with heart failure with reduced ejection fraction is quite common. In some places this might be a change in practice. With increased use of IV iron therapy there could be a reduction in hospitalisation.
Treatment combinations for heart failure with mildly reduced ejection fraction
Recommendations 1.5.1 and 1.5.2
Why the committee made the recommendations
Evidence suggested each of the following medicines reduce hospitalisation for heart failure, and possibly mortality, in people with heart failure with mildly reduced ejection fraction: angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), beta-blocker and mineralocorticoid receptor antagonist (MRA). In practice, an ACE inhibitor and ARB would not be prescribed together because of the lack of additional benefit and risk of adverse events. There was no cost-effectiveness evidence for these medicines, but all are relatively cheap in their generic form.
Evidence comparing use of an angiotensin receptor-neprilysin inhibitor (ARNI) with use of an ARB for treating heart failure with mildly reduced ejection fraction showed no difference in mortality rates. Economic evidence also showed that ARNIs were not cost effective for this population group and so were not recommended.
The committee did not review the evidence for sodium-glucose cotransporter-2 (SGLT2) inhibitors because the NICE technology appraisals 929 and 902 already recommend them as treatment options for people with heart failure with mildly reduced ejection fraction. The committee therefore agreed they should be considered alongside the other medicines.
How the recommendations might affect practice
Although this is a new recommendation for NICE, most people in this population will already be receiving a combination of these medicines, if not contraindicated and depending on comorbidities. Where there is an impact, it will include extra staff time for consultations to establish the correct combination and dose of each of medicine. However, there should be a reduction in hospitalisation for heart failure.
Treatment combinations for heart failure with preserved ejection fraction
Why the committee made the recommendation
Evidence showed treatment with a mineralocorticoid receptor antagonist (MRA) reduced hospitalisation for heart failure and may also improve all-cause and cardiovascular mortality in people with heart failure with preserved ejection fraction. However, there was an increased risk of hyperkalaemia. Although this requires careful monitoring and management the committee agreed this should not prevent them from recommending MRAs for this population group.
The committee did not review the evidence for sodium-glucose cotransporter-2 (SGLT2) inhibitors because the NICE technology appraisals 929 and 902 already recommend them as treatment options for people with heart failure with preserved ejection fraction. The committee therefore agreed they should be considered alongside MRAs.
How the recommendation might affect practice
This is a significant change in practice. The impact will include staff time for consultation to establish the correct dose of MRA and treatment of hyperkalaemia. However, there is likely to be a reduction in hospitalisation for heart failure.
Starting and monitoring medicine use
Recommendations 1.7.1 and 1.7.2, recommendations 1.7.3 to 1.7.5 and 1.7.7 and 1.7.8 and recommendations 1.7.10, 1.7.11 and 1.7.13
Why the committee made the recommendations
The order in which the medicines should be prescribed should be based on the presenting symptoms, comorbidities and past medical history and the preferences of the person, for example, expected side effects.
It is not necessary to optimise the dose of a medicine before introducing another. How quickly to introduce the medicines depends on a number of factors including symptoms, frailty, blood pressure and renal function.
Based on their experience and expertise, the committee proposed that ARNIs could be prescribed by primary care prescribers on the advice of a heart failure specialist to avoid unnecessary delays to treatment.
Evidence showed that angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor-neprilysin inhibitors (ARNIs), angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor antagonists (MRAs) can affect renal function and electrolyte levels. However, these risks can be managed by measuring a person's electrolyte levels and renal function at baseline and at regular intervals or after increasing their dose. Local guidelines should be followed rather than automatically discontinuing a medicine if there is a rise in serum creatinine of more than 50% or potassium concentrations increase to more than 5.5 mmol per litre.
The importance of measuring blood pressure after each dose increment was also stressed by the committee as postural hypotension is a common cause of hospital admission in older people.
Beta-blockers can affect heart rate and rhythm. The committee agreed, based on their expertise and experience, that a 12-lead ECG should be undertaken in anyone with a heart rate of less than 60 beats per minute before prescribing them a beta-blocker.
The committee supported the current clinical practice of not offering a beta blocker if a person has second- or third-degree heart block or bradycardia, that is a heart rate of less than 50 beats per minute. They discussed using beta blockers in symptomatic people with bradycardia, and agreed that repeating a 12-lead ECG after each dose increment was a reasonable safety measure to ensure early detection of any new arrhythmias or conduction abnormalities that could indicate intolerance to the increased dose.
How the recommendation might affect practice
The recommendations reflect current practice but might increase prescribing of ARNIs by dropping the requirement that these medicines should be initiated by a heart failure specialist.
Return to recommendations 1.7.1 and 1.7.2
Return to recommendations 1.7.3 to 1.7.5 and 1.7.7 and 1.7.8