Heart failure with reduced ejection fraction (HFrEF)

The type of heart failure in which the left side of the heart is weak and cannot pump enough blood out. NHLBI says it is diagnosed when the left ventricle pushes out 40% or less of its blood on each beat. Three medicine trials in this atlas (DAPA-HF, EMPEROR-Reduced and PARADIGM-HF) enrolled people with an ejection fraction of 40% or less. A registry of US outpatients with this type found that many were not prescribed each recommended medicine class or were not taking target doses.

Also called HFrEF · Systolic heart failure

Condition
In this atlas

Overview

Technical summary

Defined here by the trial entry rule of an ejection fraction of 40% or less (DAPA-HF, EMPEROR-Reduced and PARADIGM-HF abstracts) and by the NHLBI diagnosis page, which also says 40% or less. NHLBI says long-term conditions that harm the heart muscle, for example coronary heart disease and heart attack, are the main cause of this type. NHLBI lists diuretics and aldosterone antagonists, ACE inhibitors or ARBs, beta blockers and other medicines as commonly used for it. The MeSH heading Heart Failure, Systolic (D054143) is wider than this record and is a broad match.

Classification codes

MeSH read 2026-10-14 D054143

Burden

No burden claims are published.

Claims and evidence

No claims are published for this condition yet.

Clinical links

Each link reports what one cited claim says about one population. "Evaluated for" means studied, not shown to work. These links do not show that anything is effective or right for you.

Claim, not a settled fact Treated by: Dapagliflozin (Claimed to treat, seen from the other side)
Applies to Adult
- Patients with New York Heart Association class II, III or IV heart failure and an ejection fraction of 40% or less, who were taking recommended heart-failure therapy. The registry gives a minimum age of 18 years (its maximum age field reads 130 years). The abstract says findings were similar in people with and without diabetes.
- Not stated in the abstract. The registry record is not read for setting.
- Multinational: the registry lists 20 countries, including the United States, Canada, Brazil, China, India, Japan, Russia and several European countries.
- Adults, 18 years and over (registry minimum age). The abstract gives no mean age.
Follow-up Median 18.2 months (abstract). The registry gives the primary outcome time frame as up to 27.8 months.
In DAPA-HF, adults with class II, III or IV heart failure and an ejection fraction of 40% or less took dapagliflozin 10 mg once daily or placebo, in addition to recommended therapy. Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 people (16.3%) taking dapagliflozin and 502 of 2371 (21.2%) taking placebo (hazard ratio 0.74, 95% CI 0.65 to 0.85). The primary outcome was worsening heart failure, meaning a hospitalization or an urgent visit that led to intravenous heart-failure treatment, or death from cardiovascular causes. Death from cardiovascular causes occurred in 227 people (9.6%) and 273 (11.5%) respectively (hazard ratio 0.82, 95% CI 0.69 to 0.98), and death from any cause in 276 (11.6%) and 329 (13.9%) (hazard ratio 0.83, 95% CI 0.71 to 0.97). The authors report that findings in people with diabetes were similar to those in people without it, and that adverse events related to volume depletion, kidney dysfunction and low blood sugar did not differ between the groups.
Limitations. One placebo-controlled trial funded by AstraZeneca, which is also the registry lead sponsor. The numbers come from the PubMed abstract; the full text, supplementary tables and the registry results section were not read, so no subgroup counts are given and the abstract gives no counts for the adverse events it mentions. Median follow-up was 18.2 months, so the claim says nothing about longer use. Entry age, setting and exclusion criteria were not read. No certainty rating was assessed.
Claim, not a settled fact Treated by: Empagliflozin (Claimed to treat, seen from the other side)
Applies to Adult
- Patients with class II, III or IV heart failure and an ejection fraction of 40% or less, who were taking recommended therapy. The registry gives a minimum age of 18 years. The abstract says the effect on the primary outcome was consistent in people with and without diabetes.
- Not stated in the abstract. The registry record is not read for setting.
- Multinational: the registry lists many countries across several continents.
- Adults, 18 years and over (registry minimum age). The abstract gives no mean age.
Follow-up Median 16 months (abstract).
In EMPEROR-Reduced, adults with class II, III or IV heart failure and an ejection fraction of 40% or less took empagliflozin 10 mg once daily or placebo, in addition to recommended therapy. Over a median of 16 months, the primary outcome, cardiovascular death or hospitalization for worsening heart failure, occurred in 361 of 1863 people (19.4%) taking empagliflozin and 462 of 1867 (24.7%) taking placebo (hazard ratio 0.75, 95% CI 0.65 to 0.86). The authors report that the effect was consistent in people with and without diabetes. The total number of hospitalizations for heart failure was lower with empagliflozin (hazard ratio 0.70, 95% CI 0.58 to 0.85), and the yearly decline in estimated glomerular filtration rate was slower, at -0.55 against -2.28 ml per minute per 1.73 m2 of body surface area per year. Uncomplicated genital tract infection was reported more often with empagliflozin.
Limitations. One double-blind trial funded by Boehringer Ingelheim and Eli Lilly. The numbers come from the PubMed abstract; the full text, tables and registry results were not read. The abstract says patients were randomized but gives no age, setting or exclusion criteria, and no counts for infection. Median follow-up was 16 months. No certainty rating was assessed.
Claim, not a settled fact Treated by: Sacubitril/valsartan (combination) (Claimed to treat, seen from the other side)
Applies to Adult
- Patients with class II, III or IV heart failure and an ejection fraction of 40% or less, who were taking recommended therapy. The registry says randomization followed a single-blind run-in period of 5 to 10 weeks in which patients took enalapril and then LCZ696, and it gives a minimum age of 18 years. People who could not tolerate the run-in are therefore not in the randomized groups.
- Not stated in the abstract. The registry record is not read for setting.
- Multinational: the registry lists many countries across the Americas, Europe, Africa and Asia.
- Adults, 18 years and over (registry minimum age).
Follow-up Median 27 months at the early stop (abstract).
In PARADIGM-HF, adults with class II, III or IV heart failure and an ejection fraction of 40% or less took LCZ696 200 mg twice daily, a combination of sacubitril and valsartan, or enalapril 10 mg twice daily, in addition to recommended therapy. The trial was stopped early, after a median follow-up of 27 months, because the prespecified boundary for overwhelming benefit with LCZ696 had been crossed. At closure, the primary outcome, death from cardiovascular causes or hospitalization for heart failure, had occurred in 914 people (21.8%) in the LCZ696 group and 1117 (26.5%) in the enalapril group (hazard ratio 0.80, 95% CI 0.73 to 0.87). Death from any cause occurred in 711 people (17.0%) and 835 (19.8%) (hazard ratio 0.84, 95% CI 0.76 to 0.93), and death from cardiovascular causes in 558 (13.3%) and 693 (16.5%) (hazard ratio 0.80, 95% CI 0.71 to 0.89). Hypotension and nonserious angioedema were more common with LCZ696; renal impairment, hyperkalemia and cough were less common than with enalapril.
Limitations. One double-blind trial funded by Novartis, stopped early for benefit, which can overstate an effect. The comparator was enalapril and not placebo, and the abstract says the trial was designed to detect a difference in deaths from cardiovascular causes while its primary outcome was a composite. The registry says patients first completed a single-blind run-in on enalapril and then LCZ696, so people who could not tolerate either were not randomized. The numbers come from the PubMed abstract; the full text, tables and registry results were not read. The abstract says LCZ696 and does not name sacubitril; the PubMed record indexes LCZ696 as the sacubitril and valsartan drug combination. The abstract gives no counts for the adverse events. No certainty rating was assessed.

Record details

Record id: cardio:hfref
Content hash: 44d3c7379853de12657ae68aa4954a44575316494ccc554014b463fec888d067