What is the initial treatment for heart failure, specifically for patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)?

From the Guidelines

The initial treatment for heart failure with reduced ejection fraction (HFrEF) should include a combination of medications such as ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, as well as consideration of SGLT2 inhibitors, while heart failure with preserved ejection fraction (HFpEF) treatment focuses on symptom management with diuretics and careful management of comorbidities, with recent evidence supporting the use of SGLT2 inhibitors in HFpEF as well. The treatment approach for heart failure varies significantly based on whether the patient has HFrEF or HFpEF. For HFrEF patients, the essential medications include inhibitors of the renin–angiotensin system, neprilysin inhibitors (such as sacubitril/valsartan), beta-adrenergic blockers (like carvedilol, metoprolol succinate, and bisoprolol), and mineralocorticoid receptor antagonists, as these have been shown to reduce the risk of death and hospitalization 1. In contrast, HFpEF treatment is more focused on managing symptoms and comorbid conditions, but recent studies have indicated that SGLT2 inhibitors can also be beneficial in reducing hospitalizations and mortality in these patients 1. Key lifestyle modifications for both types of heart failure include sodium restriction, fluid management, regular physical activity, and smoking cessation. The choice of specific medications and their dosages should be tailored to the individual patient's needs and clinical status, with consideration of the latest clinical guidelines and evidence-based practices 1. It's also important to note that the treatment landscape for heart failure is continuously evolving, with new therapies and updated guidelines being developed, such as the use of SGLT2 inhibitors in both HFrEF and HFpEF, highlighting the need for ongoing education and adaptation in clinical practice 1.

From the FDA Drug Label

Spironolactone tablets are indicated for treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure. 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.

The initial treatment for heart failure with reduced ejection fraction (HFrEF) may include medications such as spironolactone and enalapril.

• Spironolactone is indicated for the treatment of NYHA Class III-IV heart failure and reduced ejection fraction to increase survival, manage edema, and reduce the need for hospitalization for heart failure 2.
• Enalapril has been shown to decrease systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure and heart size, and increase cardiac output and exercise tolerance in patients with heart failure 3. However, the FDA drug label does not provide direct information on the initial treatment for heart failure with preserved ejection fraction (HFpEF).

From the Research

Initial Treatment for Heart Failure

The initial treatment for heart failure, specifically for patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), varies depending on the underlying cause and severity of the condition.

• For HFrEF, the following treatments are recommended:

  • Diuretics as the first-line drugs to treat volume overload 4
  • Angiotensin-converting enzyme (ACE) inhibitors and β-blockers to reduce morbidity and mortality 4, 5
  • Angiotensin II receptor blockers (ARBs) if intolerant to ACE inhibitors 4
  • Sacubitril/valsartan as an alternative to ACE inhibitors or ARBs in patients with chronic symptomatic HFrEF class II or III 4
  • Aldosterone antagonists in selected patients with class II-IV HF who can be carefully monitored for renal function and potassium concentration 4, 6
  • Isosorbide dinitrate plus hydralazine in patients self-described as African Americans with class II-IV HF being treated with diuretics, ACE inhibitors, and β-blockers 4
  • Ivabradine in selected patients with HFrEF 4, 7

• For HFpEF, there is currently no firmly evidence-based treatment, but several new pharmacological and device treatments are being evaluated in clinical trials 5, 8

  • Emerging drug strategies include endothelial nitric oxide synthase activators, If current inhibitors, matrix metalloproteinase 9 inhibitors, and nitroxyl donors 8
  • LCZ696, a combination drug of angiotensin II receptor blocker and neprilysin inhibitor, and the aldosterone receptor antagonist spironolactone are currently in clinical trial for treating HFpEF 8

Treatment Goals

The goals of treatment for heart failure include improving symptoms, reducing hospital admissions, and increasing survival.

• Treatment strategies should be individualized based on the patient's underlying condition, comorbidities, and response to treatment 4, 5, 6
• Regular monitoring of renal function and potassium concentration is necessary in patients treated with certain medications, such as ACE inhibitors, ARBs, and aldosterone antagonists 4, 6