What is the first-line medication for heart failure with reduced ejection fraction (HFrEF)?

From the Guidelines

The first-line medications for heart failure with reduced ejection fraction (HFrEF) include a combination of four cornerstone therapies: an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor-neprilysin inhibitor (ARNI), a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor. These medications should be initiated at low doses and gradually titrated to target doses as tolerated. According to the most recent guidelines 1, ACEi/ARNIs, such as sacubitril/valsartan, reduce afterload and prevent adverse cardiac remodeling by blocking the renin-angiotensin-aldosterone system. Beta-blockers, such as carvedilol, metoprolol succinate, or bisoprolol, reduce heart rate, decrease myocardial oxygen demand, and improve ventricular function over time. MRAs, such as spironolactone or eplerenone, block aldosterone receptors, reducing fibrosis and sodium retention. SGLT2 inhibitors, such as empagliflozin or dapagliflozin, provide additional benefits through multiple mechanisms, including improved cardiac energetics and reduced cardiac preload.

Some key points to consider when initiating these medications include:

• Starting with low doses and gradually titrating to target doses as tolerated
• Monitoring for potential side effects, such as hyperkalemia, and adjusting medications accordingly
• Considering the use of ARNIs, such as sacubitril/valsartan, in place of ACEi for patients who remain symptomatic despite optimal treatment with an ACEi, a beta-blocker, and an MRA
• Using SGLT2 inhibitors, such as empagliflozin or dapagliflozin, in addition to the other three cornerstone therapies to provide additional benefits

The evidence supporting the use of these four cornerstone therapies is strong, with studies demonstrating significant reductions in mortality, hospitalizations, and improvements in quality of life in patients with HFrEF 1. Overall, the use of these medications as first-line therapy for HFrEF is supported by the most recent guidelines and evidence-based research.

From the FDA Drug Label

In trials in patients treated with digitalis and diuretics, treatment with enalapril resulted in decreased systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure and heart size, and increased cardiac output and exercise tolerance. In a multicenter, placebo-controlled clinical trial, 2,569 patients with all degrees of symptomatic heart failure and ejection fraction ≤35 percent were randomized to placebo or enalapril and followed for up to 55 months (SOLVD-Treatment) Use of enalapril was associated with an 11 percent reduction in all-cause mortality and a 30 percent reduction in hospitalization for heart failure.

The first-line medication for heart failure with reduced ejection fraction (HFrEF) is enalapril, an ACE inhibitor, as it has been shown to reduce mortality and hospitalization in patients with HFrEF 2.

• Key benefits of enalapril in HFrEF include:
  • Reduced systemic vascular resistance
  • Decreased blood pressure
  • Increased cardiac output
  • Improved exercise tolerance
  • Reduced mortality and hospitalization rates It is essential to note that enalapril should be used under the guidance of a healthcare professional, as its use requires careful monitoring and adjustment of dosage.

From the Research

First-Line Medication for Heart Failure with Reduced Ejection Fraction (HFrEF)

The first-line medication for HFrEF includes several classes of drugs that aim to reduce mortality and prevent hospitalizations. The primary goals of treatment are to improve cardiac function, reduce symptoms, and enhance quality of life.

• Diuretics: Diuretics are the first-line drugs in the treatment of patients with HFrEF and volume overload 3.
• Angiotensin-Converting Enzyme (ACE) Inhibitors: ACE inhibitors, such as enalapril, lisinopril, and captopril, are recommended for all patients with HFrEF, unless contraindicated 3, 4.
• Beta-Blockers: Beta-blockers, such as carvedilol, metoprolol succinate, and bisoprolol, are also recommended for all patients with HFrEF, unless contraindicated 3, 4.
• Angiotensin II Receptor Blockers (ARBs): ARBs, such as candesartan and valsartan, can be used as an alternative to ACE inhibitors in patients who are intolerant to ACE inhibitors due to cough or angioedema 3.
• Angiotensin Receptor-Neprilysin Inhibitors (ARNIs): ARNIs, such as sacubitril/valsartan, can be used instead of ACE inhibitors or ARBs in patients with chronic symptomatic HFrEF class II or III to further reduce morbidity and mortality 3, 5, 4.
• Mineralocorticoid Receptor Antagonists (MRAs): MRAs, such as spironolactone and eplerenone, can be added to the treatment regimen in selected patients with HFrEF, particularly those with more severe symptoms or signs of volume overload 3, 4, 6.
• Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2is): SGLT2is, such as empagliflozin and canagliflozin, have been shown to reduce the risk of hospitalization for heart failure and cardiovascular death in patients with HFrEF, and can be considered as an additional treatment option 7, 6.

Treatment Approach

The treatment approach for HFrEF should be individualized, taking into account the patient's symptoms, comorbidities, and renal function. A combination of medications from different classes may be necessary to achieve optimal treatment goals. Regular monitoring of the patient's condition, including renal function, potassium levels, and blood pressure, is essential to adjust the treatment regimen as needed.