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Medicines for heart failure with a reduced ejection fraction, explained

This guide explains the medicine classes used for heart failure with a reduced ejection fraction. It draws on a guideline summary, US government health pages, three trial reports and a registry report. It ends with questions to ask a care team.

Heart failure and ejection fraction

  • Heart failure means that the heart cannot pump enough oxygen-rich blood to meet the body's needs.1
  • It does not mean that the heart has stopped or is about to stop.2
  • NHLBI says ejection fraction is the share of the left ventricle's blood that is pumped out with each heartbeat.3, 4
  • NHLBI says an ejection fraction of 40% or less means heart failure with a reduced ejection fraction (HFrEF).5, 6
  • An ACC summary of a 2022 guideline gives the same cut-off.7
  • MedlinePlus says there is no cure for heart failure, but that treatment can help people live longer with fewer symptoms.8
  • It also says heart failure usually gets worse over time, even with treatment, so treatment is likely to be needed for life.9

The four classes in a 2022 guideline summary

  • An ACC summary of the 2022 heart failure guideline of the AHA, ACC and HFSA says guideline-directed medical therapy includes four classes of medicine.10
  • The four classes are renin-angiotensin system inhibitors, beta blockers, mineralocorticoid receptor antagonists (MRAs) and SGLT2 inhibitors.10
  • The summary says guideline-directed medical therapy should be considered for people with current or past heart failure, whatever their ejection fraction.10
  • The summary does not say that all four classes apply at every ejection fraction.10
  • In the summary, the first-choice ARNI statement and the class 1a SGLT2 inhibitor statement apply to reduced ejection fraction.11, 12
  • The summary gives no doses, no order for starting the classes, and no class of recommendation for its four-class statement.10
  • PubMed lists three corrections to the guideline, whose text this atlas has not read.10

Renin-angiotensin system inhibitors: ARNIs, ACE inhibitors and ARBs

  • This class has three types: ARNIs (angiotensin receptor-neprilysin inhibitors), ACE inhibitors and ARBs (angiotensin receptor blockers).10
  • The summary recommends an ARNI as the first-choice medicine in this class to lower illness and death in HFrEF.11
  • It says an ACE inhibitor is recommended when an ARNI is not feasible; an ARB is recommended for people who cannot take an ACE inhibitor and when an ARNI is not feasible.11
  • For people with symptoms and HFrEF who tolerate an ACE inhibitor or ARB, it also recommends switching to an ARNI for a further drop in illness and death.13
  • NHLBI lists ACE inhibitors and ARBs among medicines commonly used for HFrEF.14, 15
  • It describes them as medicines that relax the blood vessels, which it says eases the heart's pumping.15
  • NHLBI's list names ACE inhibitors and ARBs but not ARNIs.15
  • NHLBI lists low blood pressure, a cough and a short-term drop in kidney function among the possible side effects of these medicines.16

One trial of an ARNI

  • A 2014 trial enrolled 8442 people with class II, III or IV heart failure and an ejection fraction of 40% or less.17, 18, 19
  • It compared an ARNI called LCZ696 with enalapril.20
  • Both groups also received recommended therapy.21
  • The report says enalapril had improved survival in earlier studies of such patients.22
  • A company paid for the trial.23, 24
  • The trial was stopped early, after a median follow-up of 27 months, because its boundary for overwhelming benefit with the ARNI had been crossed.25, 26
  • By then, cardiovascular death or admission to hospital for heart failure had happened in 21.8% of people taking the ARNI and 26.5% of those taking enalapril.27, 28, 29
  • Low blood pressure and angioedema that was not serious were more common with the ARNI than with enalapril.30
  • Kidney impairment, high potassium and cough were less common with the ARNI.31

Beta blockers

  • NHLBI lists beta blockers among the medicines commonly used for HFrEF.32
  • It describes beta blockers as medicines that slow the heart rate, which it says makes the heart's pumping easier.32
  • For HFrEF, NHLBI adds that medicines that slow the heart rate can help keep heart failure from worsening over the long term.32
  • NHLBI's side-effect list for this group, which includes ivabradine, mentions high blood pressure, fuzzy vision, bright halos and a heart rate that is slow or irregular.33

Mineralocorticoid receptor antagonists (MRAs)

  • NHLBI describes aldosterone antagonists, giving spironolactone as an example.34, 35
  • NHLBI lists them among medicines commonly used for HFrEF.14, 34
  • The US National Library of Medicine's vocabulary used the heading aldosterone antagonists from 1966 to 2012, and has used mineralocorticoid receptor antagonists since 2013.36, 37
  • NHLBI describes diuretics and aldosterone antagonists as medicines that take extra sodium and fluid out of the body, so the heart has less blood to pump.34, 35, 38
  • NHLBI lists kidney disease and high levels of potassium as possible side effects of aldosterone antagonists.34, 39

SGLT2 inhibitors

  • NHLBI says SGLT-2 inhibitors and GLP agonists are two newer groups of medicines approved for people with diabetes, to lower blood sugar.40, 41
  • On a page last updated in March 2022, NHLBI's list of newer medicines for HFrEF says these two groups may also reduce hospital admissions for heart failure, and that research on using them for heart failure was ongoing.42, 43, 44
  • The ACC summary recommends an SGLT2 inhibitor for people with symptoms and chronic HFrEF, to reduce hospital admissions and cardiovascular death, whether or not they have type 2 diabetes.12
  • It adds that SGLT2 inhibitors can be beneficial in mildly reduced and preserved ejection fraction as well, with a class 2a recommendation.12
  • A 2019 trial of the SGLT2 inhibitor dapagliflozin compared it with placebo in 4744 people with class II, III or IV heart failure and an ejection fraction of 40% or less.45, 46, 47, 48
  • Both groups also received recommended therapy.49
  • A company paid for this trial.50, 51
  • In this trial, worsening heart failure meant a hospitalization or an urgent visit that led to intravenous treatment for heart failure.52
  • Over a median of 18.2 months, worsening heart failure or cardiovascular death occurred in 16.3% of people taking dapagliflozin and 21.2% of those taking placebo.52, 53, 54, 55
  • The report says findings in people with diabetes were similar to those in people without diabetes.56
  • It also says adverse events related to volume depletion, kidney dysfunction and low blood sugar did not differ between the groups.57
  • A 2020 trial of the SGLT2 inhibitor empagliflozin compared it with placebo in 3730 people with class II, III or IV heart failure and an ejection fraction of 40% or less.45, 58, 59, 60
  • Both groups also received recommended therapy.61
  • Two companies paid for this trial.62, 63, 64
  • Over a median of 16 months, cardiovascular death or admission to hospital for worsening heart failure occurred in 19.4% of people taking empagliflozin and 24.7% of those taking placebo.65, 66, 67
  • The report says the effect was consistent whether or not people had diabetes.68
  • It also says genital tract infection without complications was reported more often with empagliflozin.69

How these medicines were used in one US registry

  • The CHAMP-HF registry report, published in 2018, covered 3518 outpatients in the United States who had chronic HFrEF and took at least one heart failure medicine by mouth.70, 71, 72, 73
  • The abstract names ACE inhibitors, ARBs, ARNIs, beta blockers and MRAs, but not SGLT2 inhibitors.74, 75
  • Among eligible patients, 27% were not prescribed an ACE inhibitor, ARB or ARNI, 33% a beta blocker, and 67% an MRA.76
  • Among those prescribed them, 17% were taking target doses of an ACE inhibitor or ARB, 14% of an ARNI, 28% of a beta blocker and 77% of an MRA.76
  • Among patients eligible for all these classes, 1% were taking target doses of an ACE inhibitor, ARB or ARNI, a beta blocker and an MRA at once.76
  • In its adjusted models, older age, lower blood pressure, more severe functional class, kidney insufficiency and a recent hospital stay for heart failure generally went with lower medication use or dose.77, 78
  • The abstract does not say why a medicine was not prescribed.76

Questions to ask

  1. Which of these four medicine classes are part of my treatment?
  2. Which of these classes apply to my type of heart failure, and why?
  3. What is my ejection fraction, and does it fall in the range these sources call reduced?
  4. Would an ARNI be an option for me, or am I already taking a medicine from this class?
  5. Does the SGLT2 inhibitor recommendation apply to me, with or without diabetes?
  6. What side effects should I watch for with each of my medicines?
  7. How are the doses of my medicines chosen?
  8. Do the results of these trials apply to people like me?

Sources

  1. MedlinePlus health topic: Heart Failure Webpage, MedlinePlus, National Library of Medicine, Summary, What is heart failure, sentence 1. Retrieved .
  2. MedlinePlus health topic: Heart Failure Webpage, MedlinePlus, National Library of Medicine, Summary, What is heart failure, sentence 2. Retrieved .
  3. NHLBI: Heart Failure: Diagnosis Webpage, National Heart, Lung, and Blood Institute (NIH), Diagnosis, ejection fraction section, sentence 2, fragment 1 of 2. Retrieved .
  4. NHLBI: Heart Failure: Diagnosis Webpage, National Heart, Lung, and Blood Institute (NIH), Diagnosis, ejection fraction section, sentence 2, fragment 2 of 2. Retrieved .
  5. NHLBI: Heart Failure: Diagnosis Webpage, National Heart, Lung, and Blood Institute (NIH), Diagnosis, ejection fraction section, sentence 4, fragment 1 of 2. Retrieved .
  6. NHLBI: Heart Failure: Diagnosis Webpage, National Heart, Lung, and Blood Institute (NIH), Diagnosis, ejection fraction section, sentence 4, fragment 2 of 2. Retrieved .
  7. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Guideline, Circulation, Key perspective 1, classification list (HFrEF). Retrieved .

    Source problem. A cited source is corrected. Check the sources before relying on this claim.

  8. MedlinePlus health topic: Heart Failure Webpage, MedlinePlus, National Library of Medicine, Summary, What are the treatments, para 1, sentences 2 and 3. Retrieved .
  9. MedlinePlus health topic: Heart Failure Webpage, MedlinePlus, National Library of Medicine, Summary, What are the treatments, para 2. Retrieved .

  10. An ACC summary of the 2022 heart failure guideline of the AHA, ACC and HFSA says that guideline-directed medical therapy now has four classes: renin-angiotensin system inhibition (with an angiotensin receptor-neprilysin inhibitor, an ACE inhibitor or an angiotensin receptor blocker), beta blockers, mineralocorticoid receptor antagonists and SGLT2 inhibitors. It says everyone with heart failure now or in the past, whatever their ejection fraction, should be considered for this therapy.

    Applies to Recipient not specified
    • Patients with current or prior heart failure, whatever their ejection fraction, who according to the ACC summary should be considered for guideline-directed therapy. The summary gives no age limits.
    • Not stated in the ACC summary.
    • Not stated in the ACC summary (issued by American societies; jurisdiction not verified)
    • Not stated in the ACC summary
    • Gestational age Not reported
    • Postnatal age Not reported
    Follow-up Not applicable (guideline context)

    Limitations. The source is the ACC key-perspectives summary of the guideline (ACC content, hash only), not the guideline text. This is a description of what the therapy consists of and a statement that patients should be considered for it, not a recommendation to use all four classes at every ejection fraction. The statements in the summary itself limit the first-line ARNI statement and the class 1a SGLT2 inhibitor statement to heart failure with reduced ejection fraction, and give SGLT2 inhibitors class 2a in mildly reduced and preserved ejection fraction. It gives no class of recommendation for the four-class statement, no doses and no order of starting, so none is recorded and nothing here says the classes are started together. PubMed lists three corrections to the guideline; their text was not read, so it is not known whether they change anything stated here.

  11. An ACC summary of the 2022 heart failure guideline of the AHA, ACC and HFSA says an angiotensin receptor-neprilysin inhibitor (ARNI) is now recommended as the first-line renin-angiotensin system inhibitor to reduce illness and death in heart failure with reduced ejection fraction. It prints the class of recommendation as 1a. The summary adds that an ACE inhibitor is recommended when an ARNI is not feasible, and an angiotensin receptor blocker for people who cannot take an ACE inhibitor and when an ARNI is not feasible.

    Applies to Recipient not specified
    • People whose heart failure has a reduced ejection fraction, which the ACC summary defines as a left ventricular ejection fraction of 40% or less. The summary gives no age limits.
    • Not stated in the ACC summary.
    • Not stated in the ACC summary (issued by American societies; jurisdiction not verified)
    • Not stated in the ACC summary
    • Gestational age Not reported
    • Postnatal age Not reported
    Follow-up Not applicable (guideline context)

    Limitations. The summary names the ARNI class and not a medicine. Sacubitril/valsartan is the only ARNI recorded in this atlas, and its own page rests on a trial abstract that calls it an ARNI; no source read here names it in the guideline. The class of recommendation is as printed on the ACC page. No recommendation record is written for this statement, because it names the ARNI class and the atlas record is one substance. The source is the ACC summary, not the guideline text. PubMed lists three corrections to the guideline; their text was not read, so it is not known whether they change anything stated here.

  12. An ACC summary of the 2022 heart failure guideline of the AHA, ACC and HFSA says that in symptomatic patients with chronic heart failure with reduced ejection fraction, an SGLT2 inhibitor is recommended in order to cut hospital admissions and cardiovascular death, whether or not the patient has type 2 diabetes. It prints the class of recommendation as 1a. It adds that SGLT2 inhibitors can also be beneficial in heart failure with mildly reduced or preserved ejection fraction, at class 2a.

    Applies to Recipient not specified
    • Symptomatic patients with chronic heart failure with reduced ejection fraction (ejection fraction of 40% or less), with or without type 2 diabetes, as the ACC summary words the SGLT2 inhibitor statement. The summary gives no age limits.
    • Not stated in the ACC summary.
    • Not stated in the ACC summary (issued by American societies; jurisdiction not verified)
    • Not stated in the ACC summary
    • Gestational age Not reported
    • Postnatal age Not reported
    Follow-up Not applicable (guideline context)

    Limitations. The class of recommendation is as printed on the ACC page. The class 2a statement for mildly reduced and preserved ejection fraction is a different population from this claim context and is not a recommendation record here. The source is the ACC summary, not the guideline text. PubMed lists three corrections to the guideline; their text was not read, so it is not known whether they change anything stated here.

  13. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Guideline, Circulation, Key perspective 2, sentence 4. Retrieved .

    Source problem. A cited source is corrected. Check the sources before relying on this claim.

  14. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, lead-in. Retrieved .
  15. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, blood vessel medicines. Retrieved .
  16. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, blood vessel medicines, side effects. Retrieved .
  17. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Journal, PubDate, Year. Retrieved .
  18. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 1 of 4. Retrieved .
  19. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 2 of 4. Retrieved .
  20. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, BACKGROUND, sentence 1. Retrieved .
  21. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 4 of 4. Retrieved .
  22. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, BACKGROUND, sentence 2. Retrieved .
  23. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, CONCLUSIONS, last sentence. Retrieved .
  24. This Study Will Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure Registry, U.S. National Library of Medicine (ClinicalTrials.gov), protocolSection.sponsorCollaboratorsModule.leadSponsor.class. Retrieved .
  25. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 1, fragment 1 of 2. Retrieved .
  26. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 1, fragment 2 of 2. Retrieved .
  27. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 2, fragment 1 of 2. Retrieved .
  28. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 2, fragment 1 of 3. Retrieved .
  29. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 2, fragment 2 of 3. Retrieved .
  30. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 5, fragment 1 of 2. Retrieved .
  31. Angiotensin-neprilysin inhibition versus enalapril in heart failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 5, fragment 2 of 2. Retrieved .

  32. NHLBI lists beta blockers among medicines that slow the heart rate, which it says eases the work of pumping and can help keep heart failure from worsening over the long term. It names these medicines among those commonly used for heart failure with reduced ejection fraction. For the group of rate-slowing medicines, which also includes ivabradine, it lists possible side effects including a heart rate that is slow or uneven.

    Applies to Recipient not specified
    • People with heart failure with reduced ejection fraction, as the NHLBI treatment page describes the group of left-sided heart failure that its medicines list is for. The page gives no age limits and no ejection fraction cut-off on this page.
    • Not stated; the page is patient information about treatment.
    • United States (an NIH institute page; the page names no jurisdiction)
    • Not stated on the page
    • Gestational age Not reported
    • Postnatal age Not reported
    Follow-up Not applicable (guideline context)

    Limitations. The NHLBI page is cite only, so this atlas states it in its own words. The page lists side effects for the whole group, not for beta blockers alone. It gives no doses and no evidence for the claims. The NHLBI treatment page gives no numeric ejection fraction cut-off, so the context here does not state one.

  33. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, rate-slowing medicines, side effects. Retrieved .

  34. NHLBI lists aldosterone antagonists, with spironolactone as its example, among medicines commonly used for heart failure with reduced ejection fraction. It groups them with diuretics as medicines that take extra sodium and fluid out of the body, so the heart has less blood to pump. It lists kidney disease and high levels of potassium as possible side effects of aldosterone antagonists.

    Applies to Recipient not specified
    • People with heart failure with reduced ejection fraction, as the NHLBI treatment page describes the group of left-sided heart failure that its medicines list is for. The page gives no age limits and no ejection fraction cut-off on this page.
    • Not stated; the page is patient information about treatment.
    • United States (an NIH institute page; the page names no jurisdiction)
    • Not stated on the page
    • Gestational age Not reported
    • Postnatal age Not reported
    Follow-up Not applicable (guideline context)

    Limitations. NHLBI uses the term aldosterone antagonists and does not use the term mineralocorticoid receptor antagonists. This atlas treats them as one class because the NLM MeSH note on the descriptor Mineralocorticoid Receptor Antagonists points to the heading Aldosterone Antagonists for 1966 to 2012; that note is context, not a statement by NHLBI. The NHLBI page is cite only, so this atlas states it in its own words. It gives no doses, no trial evidence and no blood tests for this group. The page gives no numeric ejection fraction cut-off, so the context here does not state one.

  35. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, diuretics and aldosterone antagonists, fragment 1 of 2. Retrieved .
  36. MeSH descriptor D000451 (Mineralocorticoid Receptor Antagonists) Dataset, U.S. National Library of Medicine, publicMeSHNote.@value. Retrieved .
  37. MeSH descriptor D000451 (Mineralocorticoid Receptor Antagonists) Dataset, U.S. National Library of Medicine, label.@value. Retrieved .
  38. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, diuretics and aldosterone antagonists, fragment 2 of 2. Retrieved .
  39. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, aldosterone antagonist side effects. Retrieved .
  40. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, newer medicines, sentence 1, fragment 1 of 2. Retrieved .
  41. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, newer medicines, sentence 1, fragment 2 of 2. Retrieved .
  42. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, newer medicines, sentence 2. Retrieved .
  43. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Medicines, left-sided heart failure, newer medicines, sentence 3. Retrieved .
  44. Heart failure: treatment (National Heart, Lung, and Blood Institute) Webpage, National Heart, Lung, and Blood Institute, Page footer, last updated. Retrieved .

  45. In four separate placebo-controlled trials in adults with chronic heart failure, the primary outcome was lower with an SGLT2 inhibitor than with placebo. The primary outcome was a composite of cardiovascular death and worsening heart failure, defined slightly differently in each trial. The hazard ratios (95% confidence intervals) were: DAPA-HF, dapagliflozin, ejection fraction 40% or less, 0.74 (0.65 to 0.85); EMPEROR-Reduced, empagliflozin, 40% or less, 0.75 (0.65 to 0.86); EMPEROR-Preserved, empagliflozin, above 40%, 0.79 (0.69 to 0.90); DELIVER, dapagliflozin, above 40%, 0.82 (0.73 to 0.92). The abstracts report the benefit or its consistency in people with and without diabetes. In DELIVER, cardiovascular death on its own had a hazard ratio of 0.88 (0.74 to 1.05), and in EMPEROR-Preserved the effect was mainly related to fewer hospitalizations for heart failure. This lists four trial results side by side. It is not a pooled analysis.

    Applies to Adult
    • Adults with chronic heart failure in four separate trials: DAPA-HF and EMPEROR-Reduced (ejection fraction of 40% or less) and EMPEROR-Preserved and DELIVER (ejection fraction of more than 40%). Each trial added the SGLT2 inhibitor or placebo to recommended or usual therapy. The abstracts say findings were similar or consistent in people with and without diabetes. This context joins four trials for comparison and is not a pooled analysis.
    • Not stated in the abstract. The registry record is not read for setting.
    • Multinational trials.
    • Adults.
    Follow-up Median follow-up differs by trial: 18.2 months, 16 months, 26.2 months and 2.3 years (abstracts).

    Limitations. The hazard ratios are the trials' own and were not pooled or re-analysed. The trials differ in entry criteria, in the drug, in the definition of the primary outcome and in follow-up. All four were funded by the drug makers. Numbers come from the PubMed abstracts; full texts were not read. Harms differ by trial and are given on the trial claims (genital and urinary tract infections and low blood pressure with empagliflozin in EMPEROR-Preserved; genital tract infection with empagliflozin in EMPEROR-Reduced). No certainty rating was assessed.

  46. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Journal, PubDate, Year. Retrieved .
  47. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 1 of 4. Retrieved .
  48. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 2 of 4. Retrieved .
  49. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 4 of 4. Retrieved .
  50. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, CONCLUSIONS, last sentence. Retrieved .
  51. Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure Registry, U.S. National Library of Medicine (ClinicalTrials.gov), protocolSection.sponsorCollaboratorsModule.leadSponsor.class. Retrieved .
  52. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, METHODS, sentence 2, fragment 1 of 2. Retrieved .
  53. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, METHODS, sentence 2, fragment 2 of 2. Retrieved .
  54. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, RESULTS, sentence 1, fragment 1 of 3. Retrieved .
  55. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, RESULTS, sentence 1, fragment 2 of 3. Retrieved .
  56. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, RESULTS, sentence 4. Retrieved .
  57. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction Publication, The New England journal of medicine, Abstract, RESULTS, sentence 5. Retrieved .
  58. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Journal, PubDate, Year. Retrieved .
  59. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 1 of 4. Retrieved .
  60. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 2 of 4. Retrieved .
  61. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 1, fragment 4 of 4. Retrieved .
  62. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, CONCLUSIONS, last sentence. Retrieved .
  63. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) Registry, U.S. National Library of Medicine (ClinicalTrials.gov), protocolSection.sponsorCollaboratorsModule.leadSponsor.class. Retrieved .
  64. EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) Registry, U.S. National Library of Medicine (ClinicalTrials.gov), protocolSection.sponsorCollaboratorsModule.collaborators[0].class. Retrieved .
  65. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, METHODS, sentence 2. Retrieved .
  66. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 1, fragment 1 of 3. Retrieved .
  67. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 1, fragment 2 of 3. Retrieved .
  68. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 2. Retrieved .
  69. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure Publication, The New England journal of medicine, Abstract, RESULTS, sentence 5. Retrieved .
  70. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Journal, PubDate, Year. Retrieved .
  71. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Abstract, METHODS, sentence 1, fragment 1 of 2. Retrieved .
  72. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Abstract, METHODS, sentence 1, fragment 2 of 2. Retrieved .
  73. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Abstract, RESULTS, sentence 1. Retrieved .
  74. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Abstract, METHODS, sentence 2, fragment 1 of 2. Retrieved .
  75. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Abstract, METHODS, sentence 2, fragment 2 of 2. Retrieved .

  76. In the CHAMP-HF registry of 3518 US outpatients with chronic heart failure with reduced ejection fraction, many eligible patients were not prescribed each recommended medicine class: 27% were not prescribed an ACE inhibitor, angiotensin receptor blocker or angiotensin receptor neprilysin inhibitor, 33% were not prescribed a beta-blocker and 67% were not prescribed a mineralocorticoid receptor antagonist. Among patients who were prescribed them, few were taking target doses: 17% for ACE inhibitor or angiotensin receptor blocker, 14% for angiotensin receptor neprilysin inhibitor and 28% for beta-blocker, against 77% for a mineralocorticoid receptor antagonist. Of patients eligible for all classes, 1% were taking target doses of all of ACE inhibitor, angiotensin receptor blocker or angiotensin receptor neprilysin inhibitor, a beta-blocker and a mineralocorticoid receptor antagonist at once. The authors conclude that significant gaps in the use and dose of guideline-directed medical therapy remain.

    Applies to Adult
    • Outpatients with chronic heart failure with reduced ejection fraction who were receiving at least one oral medication for heart failure. 3518 patients from 150 primary care and cardiology practices were included. Mean age was 66 years (standard deviation 13), 29% were female, and mean ejection fraction was 29% (standard deviation 8).
    • Outpatient primary care and cardiology practices (abstract).
    • United States (abstract).
    • Adults; mean age 66 years (abstract).
    Follow-up The abstract describes baseline medicine use and dose; it gives no follow-up period and no enrollment dates.

    Limitations. An observational registry of 150 US practices; the numbers come from the PubMed abstract and describe baseline prescribing at enrollment. The abstract gives no enrollment dates, so the claim cannot say how current the figures are, and the abstract does not list SGLT2 inhibitors among the classes studied. It does not say how eligibility for each class was determined or why medicines were not prescribed, and says clinical factors such as older age, lower blood pressure, kidney insufficiency and recent hospitalization generally went with lower use or dose. The full text was not read. No certainty rating was assessed.

  77. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Abstract, RESULTS, sentence 6, fragment 1 of 2. Retrieved .
  78. Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry Publication, Journal of the American College of Cardiology, Abstract, RESULTS, sentence 6, fragment 2 of 2. Retrieved .

About this guide

Written for
Adults with heart failure with a reduced ejection fraction (HFrEF), and the people who support them
What it covers
Written from a guideline summary, US government health pages, three trial reports, a registry report and an entry in a medical vocabulary. The guideline summary and the NHLBI page date from 2022. This guide does not compare them with later guidance. It describes what the sources say and gives no advice for one person.
Pages it explains
Sources checked
2026-10-15
Next check due
2027-04-15
Reading level
Estimated grade 9.5 (target 10)

Every sentence cites a source. Words in quotation marks are the source's own; the rest is the atlas's summary.

https://cardio.openmedicalatlas.org/guides/heart-failure-medicines/ · Release f4600233112e1c27, built 2026-10-15