What is the initial treatment for a patient with heart failure and an ejection fraction (EF) of 40% according to European Society of Cardiology (ESC) guidelines?

From the Guidelines

The initial treatment for a patient with heart failure and an ejection fraction of 40% should include an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor-neprilysin inhibitor (ARNI), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and a sodium-glucose cotransporter-2 (SGLT2) inhibitor, as recommended by the European Society of Cardiology guidelines 1. The treatment approach for heart failure with reduced ejection fraction (HFrEF) involves a combination of medications that target different pathophysiological mechanisms.

• An ACEi or ARNI, such as enalapril, ramipril, or lisinopril, is recommended to reduce the risk of heart failure hospitalization and death 1.
• A beta-blocker, such as bisoprolol, carvedilol, or metoprolol succinate, is also recommended to reduce the risk of heart failure hospitalization and death 1.
• An MRA, such as spironolactone or eplerenone, is recommended for patients who remain symptomatic despite treatment with an ACEi and a beta-blocker 1.
• An SGLT2 inhibitor, such as dapagliflozin or empagliflozin, has been shown to improve outcomes in heart failure patients across the range of left ventricular ejection fraction (LVEF) and is recommended as part of the initial treatment regimen 1. These medications should be initiated at low doses and gradually titrated to target doses as tolerated, with regular monitoring of renal function, electrolytes, and blood pressure.
• Diuretics may also be added to manage fluid overload and symptoms, but are not considered disease-modifying therapy. The quadruple therapy approach is supported by the most recent European Society of Cardiology guidelines, which emphasize the importance of a comprehensive treatment strategy for patients with heart failure and reduced ejection fraction 1.

From the FDA Drug Label

Patients had to have been on an ACE inhibitor or ARB for at least four weeks and on maximally tolerated doses of beta-blockers. Patients with a systolic blood pressure of less than 100 mmHg at screening were excluded The primary objective of PARADIGM-HF was to determine whether sacubitril and valsartan, a combination of sacubitril and an RAS inhibitor (valsartan), was superior to an RAS inhibitor (enalapril) alone in reducing the risk of the combined endpoint of cardiovascular (CV) death or hospitalization for heart failure (HF) PARADIGM-HF demonstrated that sacubitril and valsartan, an combination of sacubitril and a RAS inhibitor (valsartan), was superior to a RAS inhibitor (enalapril), in reducing the risk of the combined endpoint of cardiovascular death or hospitalization for heart failure, based on a time-to-event analysis (hazard ratio [HR] 0.8; 95% confidence interval [CI], 0.73,0.87, p < 0. 0001)

The initial treatment for a patient with heart failure and an ejection fraction (EF) of 40% according to European Society of Cardiology (ESC) guidelines is sacubitril and valsartan or an ACE inhibitor (such as enalapril) in combination with a beta-blocker, as supported by the PARADIGM-HF trial 2 and 2. Sacubitril and valsartan has been shown to be superior to enalapril in reducing the risk of cardiovascular death or hospitalization for heart failure. Key points to consider include:

• The patient should be on maximally tolerated doses of beta-blockers.
• The patient should have a systolic blood pressure of at least 100 mmHg.
• Sacubitril and valsartan or an ACE inhibitor (such as enalapril) should be used in combination with other heart failure therapies as indicated.

From the Research

Initial Treatment for Heart Failure with EF 40%

According to the European Society of Cardiology (ESC) guidelines, the initial treatment for a patient with heart failure and an ejection fraction (EF) of 40% involves a combination of medications. The key components of this treatment include:

• Angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor-neprilysin inhibitors (ARNI) such as sacubitril/valsartan 3, 4, 5, 6
• Beta-blockers
• Mineralocorticoid receptor antagonists (MRA)
• SGLT2 inhibitors such as dapagliflozin or empagliflozin 7

Rationale for Sacubitril/Valsartan

The use of sacubitril/valsartan is supported by several studies that demonstrate its effectiveness in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction (HFrEF) 3, 4, 5, 6. Sacubitril/valsartan has been shown to be superior to ACE inhibitors such as enalapril in reducing the incidence of death from cardiovascular causes or first hospitalization for worsening heart failure.

Treatment Initiation and Individualization

The ESC guidelines recommend that treatment initiation of all four drug classes (ACE inhibitors/ARNI, beta-blockers, MRA, and SGLT2 inhibitors) should be fast and simultaneous 7. In some cases, the ARNI sacubitril/valsartan may be initiated even in ACE inhibitor-naïve patients. Further treatment has to be individualized, taking into account the patient's specific needs and comorbidities.

Importance of Comorbidity Management

The management of comorbidities is also an important aspect of heart failure treatment. For example, patients hospitalized for acute HF decompensation should be systematically screened for iron deficiency, as HF patients with proven iron deficiency benefit from intravenous ferric carboxymaltose 7.