The 2025 NICE Heart Failure guideline includes new recommendations for this “borderline” category, where patients
It had previously been unclear whether this group would benefit from the normal range of treatments for heart failure with reduced ejection fraction (HF-REF) or should be treated as heart failure with preserved ejection fraction (HF-PEF).
NICE recommends to consider an ACE inhibitor, beta-blocker, MRA and SGLT2 inhibitor in combination for this group.
Evidence in this area is limited, has some uncertainty, and is drawn from a variety of sources.
The table below shows some useful figures from the NICE evidence review1.
| Drug | Benefit – Absolute Risk Reduction | Type of evidence | Evidence Quality |
| ACE inhibitor | 2% ARR in total mortality
over 5 years |
Subgroup analysis from 1 trial
2512 patients |
VERY LOW |
| ARB (angiotensin receptor blocker) | 2% ARR in first hospitalisation
6% ARR in repeat hospitalisations over 3 years |
Subgroup analysis from 1 trial
1332 patients |
MODERATE |
| Beta-blocker | 2% ARR in cardiovascular mortality*
over 1.3 years |
Subgroup from IPD meta-analysis
570 patients |
LOW |
| MRA | 0.5% ARR in hospitalisation
2% ARR in cardiovascular mortality** over 3 years |
Meta-analysis of subgroups from 2 trials
2692 patients
|
VERY LOW |
| 8% ARI (absolute risk increase) in hyperkalaemia | MODERATE | ||
| SGLT2 inhibitor | 2% ARR in cardiovascular mortality
over 18 months |
Meta-analysis of 8 trials
9,635 patients |
MODERATE |
* this 2% ARR figure is a rough, illustrative approximation from an individual-patient-data meta-analysis which informed the NICE evidence review2. The nature of this kind of study means you can’t draw out truly accurate absolute risk estimates, but this figure can serve as a guide. However, this meta-analysis suggests that overall the relative benefits of beta-blockers in HFmrEF are similar to those seen for HF-PEF.
** this figure just failed to reach statistical significance
References
1)National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and management 2025 [Internet]. [London]: NICE; 2025. (NICE guideline [NG106])
2) Cleland JGF, Bunting KV, Flather MD et al; Beta-blockers in Heart Failure Collaborative Group. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials. Eur Heart J. 2018 Jan 1;39(1):26-35.
People who have an adverse event
People whose adverse event is prevented by treatment
People who were never going to have an adverse event anyway
Graphics and NNTs are rounded to the nearest integer
These three statistical terms offer three different ways of looking at the results of trial data.
Absolute Risk Reduction
This tells you how many people out of 100 who take a treatment have an adverse event prevented.
MoreThe value of the ARR changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the greater the absolute chance of benefit.
You need to think about over what time the trial data show this benefit, as it is usually assumed that more absolute risk reduction is gained over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Number Needed to Treat
This tells you how many people need to take the treatment in order for one person to avoid an adverse event.
The lower the number, the more effective the treatment.
MoreThe value of the NNT changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the smaller the NNT.
You need to think about over what time the trial data show benefit, as it is usually assumed that more benefit is gained over time and therefore the NNT will drop over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Relative Risk Reduction
This tells you the proportion of adverse events that are avoided if the entire population at risk is treated.
MoreThe value of the RRR is usually constant in people (or populations) at varying degrees of risk.
It is also usually assumed to stay constant over time.
This can be helpful, especially when thinking about population outcomes, but can be misleading for an individual person:
For example, a RRR of 25% in someone with a baseline risk of 40% would give them an ARR of 10% and an NNT of 10.
A RRR of 25% in someone with a baseline risk of 4% would give them an ARR or 1% and an NNT of 100.
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If you are a patient/member of the public, do feel free to look around, but please don’t make any changes to your treatments based on information here. If you find something which seems relevant to you, you could show this website to your healthcare professional to help a discussion.